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  Subjects -> BIOLOGY (Total: 3086 journals)
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BIOLOGY (1462 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 1720 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 21)
Achievements in the Life Sciences     Open Access   (Followers: 5)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 23)
Acta Biologica Colombiana     Open Access   (Followers: 7)
Acta Biologica Hungarica     Full-text available via subscription   (Followers: 4)
Acta Biologica Sibirica     Open Access  
Acta Biomaterialia     Hybrid Journal   (Followers: 27)
Acta Biotheoretica     Hybrid Journal   (Followers: 4)
Acta Chiropterologica     Full-text available via subscription   (Followers: 6)
acta ethologica     Hybrid Journal   (Followers: 4)
Acta Limnologica Brasiliensia     Open Access   (Followers: 3)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Musei Silesiae, Scientiae Naturales : The Journal of Silesian Museum in Opava     Open Access  
Acta Neurobiologiae Experimentalis     Open Access  
Acta Parasitologica     Hybrid Journal   (Followers: 10)
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Advances in Virus Research     Full-text available via subscription   (Followers: 5)
African Journal of Range & Forage Science     Hybrid Journal   (Followers: 6)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 1)
Ageing Research Reviews     Hybrid Journal   (Followers: 9)
Aging Cell     Open Access   (Followers: 11)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Agrokreatif Jurnal Ilmiah Pengabdian kepada Masyarakat     Open Access  
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Al-Kauniyah : Jurnal Biologi     Open Access  
Alasbimn Journal     Open Access   (Followers: 1)
AMB Express     Open Access   (Followers: 1)
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American Biology Teacher     Full-text available via subscription   (Followers: 14)
American Fern Journal     Full-text available via subscription   (Followers: 1)
American Journal of Agricultural and Biological Sciences     Open Access   (Followers: 8)
American Journal of Bioethics     Hybrid Journal   (Followers: 10)
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American Journal of Plant Sciences     Open Access   (Followers: 18)
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American Malacological Bulletin     Full-text available via subscription   (Followers: 3)
American Naturalist     Full-text available via subscription   (Followers: 70)
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Animal Cells and Systems     Hybrid Journal   (Followers: 4)
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Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3)
Annales UMCS, Biologia     Open Access   (Followers: 1)
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Annals of Human Biology     Hybrid Journal   (Followers: 5)
Annual Review of Biomedical Engineering     Full-text available via subscription   (Followers: 15)
Annual Review of Biophysics     Full-text available via subscription   (Followers: 23)
Annual Review of Cancer Biology     Full-text available via subscription   (Followers: 1)
Annual Review of Cell and Developmental Biology     Full-text available via subscription   (Followers: 37)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 13)
Annual Review of Genomics and Human Genetics     Full-text available via subscription   (Followers: 23)
Annual Review of Phytopathology     Full-text available via subscription   (Followers: 10)
Anthropological Review     Open Access   (Followers: 22)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antibiotics     Open Access   (Followers: 9)
Antioxidants     Open Access   (Followers: 4)
Antioxidants & Redox Signaling     Hybrid Journal   (Followers: 8)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apidologie     Hybrid Journal   (Followers: 4)
Apmis     Hybrid Journal   (Followers: 1)
APOPTOSIS     Hybrid Journal   (Followers: 8)
Applied Bionics and Biomechanics     Open Access   (Followers: 8)
Applied Vegetation Science     Full-text available via subscription   (Followers: 10)
Aquaculture Environment Interactions     Open Access   (Followers: 2)
Aquaculture International     Hybrid Journal   (Followers: 22)
Aquaculture Reports     Open Access   (Followers: 3)
Aquaculture, Aquarium, Conservation & Legislation - International Journal of the Bioflux Society     Open Access   (Followers: 6)
Aquatic Biology     Open Access   (Followers: 5)
Aquatic Ecology     Hybrid Journal   (Followers: 32)
Aquatic Ecosystem Health & Management     Hybrid Journal   (Followers: 14)
Aquatic Science and Technology     Open Access   (Followers: 3)
Aquatic Toxicology     Hybrid Journal   (Followers: 21)
Archaea     Open Access   (Followers: 3)
Archiv für Molluskenkunde: International Journal of Malacology     Full-text available via subscription   (Followers: 3)
Archives of Biological Sciences     Open Access  
Archives of Biomedical Sciences     Open Access   (Followers: 7)
Archives of Microbiology     Hybrid Journal   (Followers: 8)
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Archives of Oral Biology     Hybrid Journal   (Followers: 2)
Archives of Virology     Hybrid Journal   (Followers: 5)
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Arid Ecosystems     Hybrid Journal   (Followers: 2)
Arquivos do Instituto Biológico     Open Access   (Followers: 1)
Arquivos do Museu Dinâmico Interdisciplinar     Open Access  
Arthropod Structure & Development     Hybrid Journal   (Followers: 2)
Arthropods     Open Access   (Followers: 1)
Artificial DNA: PNA & XNA     Hybrid Journal   (Followers: 3)
Artificial Photosynthesis     Open Access   (Followers: 1)
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Journal of Biodiversity     Open Access   (Followers: 4)
Asian Journal of Biological Sciences     Open Access   (Followers: 3)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Developmental Biology     Open Access   (Followers: 2)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 3)
Asian Journal of Nematology     Open Access   (Followers: 4)
Asian Journal of Poultry Science     Open Access   (Followers: 3)
Australian Life Scientist     Full-text available via subscription   (Followers: 2)
Australian Mammalogy     Hybrid Journal   (Followers: 6)
Autophagy     Hybrid Journal   (Followers: 2)
Avian Biology Research     Full-text available via subscription   (Followers: 4)
Avian Conservation and Ecology     Open Access   (Followers: 11)
Bacteriology Journal     Open Access   (Followers: 1)
Bacteriophage     Full-text available via subscription   (Followers: 3)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Plant Taxonomy     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Berita Biologi     Open Access   (Followers: 1)
Between the Species     Open Access   (Followers: 1)
Bio Tribune Magazine     Hybrid Journal  
BIO Web of Conferences     Open Access  
BIO-Complexity     Open Access  
Bio-Grafía. Escritos sobre la Biología y su enseñanza     Open Access  
Bioanalytical Reviews     Hybrid Journal   (Followers: 2)
Biocatalysis and Biotransformation     Hybrid Journal   (Followers: 6)
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 15)
Biochimie     Hybrid Journal   (Followers: 7)
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Biocontrol Science and Technology     Hybrid Journal   (Followers: 5)
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Biodiversitas : Journal of Biological Diversity     Open Access  
Biodiversity : Research and Conservation     Open Access   (Followers: 26)
Biodiversity and Natural History     Open Access   (Followers: 6)
Biodiversity Data Journal     Open Access   (Followers: 3)
Biodiversity Informatics     Open Access   (Followers: 1)
Biodiversity Information Science and Standards     Open Access  
Bioedukasi : Jurnal Pendidikan Biologi FKIP UM Metro     Open Access  
Bioeksperimen : Jurnal Penelitian Biologi     Open Access  
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
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Biologia     Hybrid Journal  
Biologia on-line : Revista de divulgació de la Facultat de Biologia     Open Access  
Biological Bulletin     Partially Free   (Followers: 5)
Biological Control     Hybrid Journal   (Followers: 4)
Biological Invasions     Hybrid Journal   (Followers: 18)
Biological Journal of the Linnean Society     Hybrid Journal   (Followers: 18)
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Biological Psychiatry     Hybrid Journal   (Followers: 45)
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Biological Rhythm Research     Hybrid Journal   (Followers: 2)
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Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription  
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 40)
Biologija     Open Access  
Biology     Open Access   (Followers: 3)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Antibiotics
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  This is an Open Access Journal Open Access journal
   ISSN (Print) 2079-6382
   Published by MDPI Homepage  [198 journals]
  • Antibiotics, Vol. 7, Pages 27: High-Throughput Sequencing Analysis of the
           Actinobacterial Spatial Diversity in Moonmilk Deposits

    • Authors: Marta Maciejewska, Magdalena Całusińska, Luc Cornet, Delphine Adam, Igor Pessi, Sandrine Malchair, Philippe Delfosse, Denis Baurain, Hazel Barton, Monique Carnol, Sébastien Rigali
      First page: 27
      Abstract: Moonmilk are cave carbonate deposits that host a rich microbiome, including antibiotic-producing Actinobacteria, making these speleothems appealing for bioprospecting. Here, we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRNA amplicons. Actinobacteria was the most common phylum after Proteobacteria, ranging from 9% to 23% of the total bacterial population. Next to actinobacterial operational taxonomic units (OTUs) attributed to uncultured organisms at the genus level (~44%), we identified 47 actinobacterial genera with Rhodoccocus (4 OTUs, 17%) and Pseudonocardia (9 OTUs, ~16%) as the most abundant in terms of the absolute number of sequences. Streptomycetes presented the highest diversity (19 OTUs, 3%), with most of the OTUs unlinked to the culturable Streptomyces strains that were previously isolated from the same deposits. Furthermore, 43% of the OTUs were shared between the three studied collection points, while 34% were exclusive to one deposit, indicating that distinct speleothems host their own population, despite their nearby localization. This important spatial diversity suggests that prospecting within different moonmilk deposits should result in the isolation of unique and novel Actinobacteria. These speleothems also host a wide range of non-streptomycetes antibiotic-producing genera, and should therefore be subjected to methodologies for isolating rare Actinobacteria.
      Citation: Antibiotics
      PubDate: 2018-03-21
      DOI: 10.3390/antibiotics7020027
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 28: Isolation, Characterization, and
           Antibacterial Activity of Hard-to-Culture Actinobacteria from Cave
           Moonmilk Deposits

    • Authors: Delphine Adam, Marta Maciejewska, Aymeric Naômé, Loïc Martinet, Wouter Coppieters, Latifa Karim, Denis Baurain, Sébastien Rigali
      First page: 28
      Abstract: Cave moonmilk deposits host an abundant and diverse actinobacterial population that has a great potential for producing novel natural bioactive compounds. In our previous attempt to isolate culturable moonmilk-dwelling Actinobacteria, only Streptomyces species were recovered, whereas a metagenetic study of the same deposits revealed a complex actinobacterial community including 46 actinobacterial genera in addition to streptomycetes. In this work, we applied the rehydration-centrifugation method to lessen the occurrence of filamentous species and tested a series of strategies to achieve the isolation of hard-to-culture and rare Actinobacteria from the moonmilk deposits of the cave “Grotte des Collemboles”. From the “tips and tricks” that were tested, separate autoclaving of the components of the International Streptomyces Project (ISP) medium number 5 (ISP5) medium, prolonged incubation time, and dilution of the moonmilk suspension were found to most effectively improve colony forming units. Taxonomic analyses of the 40 isolates revealed new representatives of the Agromyces, Amycolatopsis, Kocuria, Micrococcus, Micromonospora, Nocardia, and Rhodococcus species, as well as additional new streptomycetes. The applied methodologies allowed the isolation of strains associated with both the least and most abundant moonmilk-dwelling actinobacterial operational taxonomic units. Finally, bioactivity screenings revealed that some isolates displayed high antibacterial activities, and genome mining uncovered a strong potential for the production of natural compounds.
      Citation: Antibiotics
      PubDate: 2018-03-22
      DOI: 10.3390/antibiotics7020028
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 29: Engineering of Phage-Derived Lytic Enzymes:
           Improving Their Potential as Antimicrobials

    • Authors: Carlos São-José
      First page: 29
      Abstract: Lytic enzymes encoded by bacteriophages have been intensively explored as alternative agents for combating bacterial pathogens in different contexts. The antibacterial character of these enzymes (enzybiotics) results from their degrading activity towards peptidoglycan, an essential component of the bacterial cell wall. In fact, phage lytic products have the capacity to kill target bacteria when added exogenously in the form of recombinant proteins. However, there is also growing recognition that the natural bactericidal activity of these agents can, and sometimes needs to be, substantially improved through manipulation of their functional domains or by equipping them with new functions. In addition, often, native lytic proteins exhibit features that restrict their applicability as effective antibacterials, such as poor solubility or reduced stability. Here, I present an overview of the engineering approaches that can be followed not only to overcome these and other restrictions, but also to generate completely new antibacterial agents with significantly enhanced characteristics. As conventional antibiotics are running short, the remarkable progress in this field opens up the possibility of tailoring efficient enzybiotics to tackle the most menacing bacterial infections.
      Citation: Antibiotics
      PubDate: 2018-03-22
      DOI: 10.3390/antibiotics7020029
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 30: Complex Regulatory Networks Governing
           Production of the Glycopeptide A40926

    • Authors: Rosa Alduina, Margherita Sosio, Stefano Donadio
      First page: 30
      Abstract: Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoBR, have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.
      Citation: Antibiotics
      PubDate: 2018-04-05
      DOI: 10.3390/antibiotics7020030
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 31: Complementation Studies of Bacteriophage λ
           O Amber Mutants by Allelic Forms of O Expressed from Plasmid, and O-P
           Interaction Phenotypes

    • Authors: Sidney Hayes, Karthic Rajamanickam, Connie Hayes
      First page: 31
      Abstract: λ genes O and P are required for replication initiation from the bacteriophage λ origin site, oriλ, located within gene O. Questions have persisted for years about whether O-defects can indeed be complemented in trans. We show the effect of original null mutations in O and the influence of four origin mutations (three are in-frame deletions and one is a point mutation) on complementation. This is the first demonstration that O proteins with internal deletions can complement for O activity, and that expression of the N-terminal portion of gene P can completely prevent O complementation. We show that O-P co-expression can limit the lethal effect of P on cell growth. We explore the influence of the contiguous small RNA OOP on O complementation and P-lethality.
      Citation: Antibiotics
      PubDate: 2018-04-05
      DOI: 10.3390/antibiotics7020031
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 32: Our Evolving Understanding of the Mechanism
           of Quinolones

    • Authors: Arnaud Gutierrez, Jonathan Stokes, Ivan Matic
      First page: 32
      Abstract: The maintenance of DNA supercoiling is essential for the proper regulation of a plethora of biological processes. As a consequence of this mode of regulation, ahead of the replication fork, DNA replication machinery is prone to introducing supercoiled regions into the DNA double helix. Resolution of DNA supercoiling is essential to maintain DNA replication rates that are amenable to life. This resolution is handled by evolutionarily conserved enzymes known as topoisomerases. The activity of topoisomerases is essential, and therefore constitutes a prime candidate for targeting by antibiotics. In this review, we present hallmark investigations describing the mode of action of quinolones, one of the antibacterial classes targeting the function of topoisomerases in bacteria. By chronologically analyzing data gathered on the mode of action of this imperative antibiotic class, we highlight the necessity to look beyond primary drug-target interactions towards thoroughly understanding the mechanism of quinolones at the level of the cell.
      Citation: Antibiotics
      PubDate: 2018-04-08
      DOI: 10.3390/antibiotics7020032
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 33: The Cellular Mechanisms that Ensure an
           Efficient Secretion in Streptomyces

    • Authors: Sonia Gullón, Rafael Mellado
      First page: 33
      Abstract: Gram-positive soil bacteria included in the genus Streptomyces produce a large variety of secondary metabolites in addition to extracellular hydrolytic enzymes. From the industrial and commercial viewpoints, the S. lividans strain has generated greater interest as a host bacterium for the overproduction of homologous and heterologous hydrolytic enzymes as an industrial application, which has considerably increased scientific interest in the characterization of secretion routes in this bacterium. This review will focus on the secretion machinery in S. lividans.
      Citation: Antibiotics
      PubDate: 2018-04-14
      DOI: 10.3390/antibiotics7020033
      Issue No: Vol. 7, No. 2 (2018)
       
  • Antibiotics, Vol. 7, Pages 4: Characteristics of Pediatric Antimicrobial
           Stewardship Programs: Current Status of the Sharing Antimicrobial Reports
           for Pediatric Stewardship (SHARPS) Collaborative

    • Authors: Christopher McPherson, Brian Lee, Cindy Terrill, Adam Hersh, Jeffrey Gerber, Matthew Kronman, Jason Newland
      First page: 4
      Abstract: In response to the growing epidemic of antibiotic-resistant bacterial infections, antimicrobial stewardship programs (ASP) have been rapidly implemented in the United States (US). This study examines the prevalence of the Centers for Disease Control and Prevention’s (CDC) seven core elements of a successful ASP within a large subset of US Children’s Hospitals. In 2016, a survey was conducted of 52 pediatric hospitals assessing the presence of the seven core elements: leadership commitment, accountability, drug expertise, action, tracking, reporting, and education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%) included all seven core elements. Physician accountability (87%) and a dedicated ASP pharmacist or drug expert (88%) were present in the vast majority of hospitals. However, substantial variability existed in the financial support allotted to these positions. This variability did not predict program actions, tracking, reporting, and education. When compared with previous surveys, these results document a dramatic increase in the prevalence and resources of pediatric stewardship programs, although continued expansion is warranted. Further research is required to understand the feasibility of various core stewardship activities and the impact on patient outcomes in the setting of finite resources.
      Citation: Antibiotics
      PubDate: 2018-01-25
      DOI: 10.3390/antibiotics7010004
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 5: Screening of E. coli β-clamp Inhibitors
           Revealed that Few Inhibit Helicobacter pylori More Effectively: Structural
           and Functional Characterization

    • Authors: Preeti Pandey, Vijay Verma, Suman Dhar, Samudrala Gourinath
      First page: 5
      Abstract: The characteristic of interaction with various enzymes and processivity-promoting nature during DNA replication makes β-clamp an important drug target. Helicobacter pylori (H. pylori) have several unique features in DNA replication machinery that makes it different from other microorganisms. To find out whether difference in DNA replication proteins behavior accounts for any difference in drug response when compared to E. coli, in the present study, we have tested E. coli β-clamp inhibitor molecules against H. pylori β-clamp. Various approaches were used to test the binding of inhibitors to H. pylori β-clamp including docking, surface competition assay, complex structure determination, as well as antimicrobial assay. Out of five shortlisted inhibitor molecules on the basis of docking score, three molecules, 5-chloroisatin, carprofen, and 3,4-difluorobenzamide were co-crystallized with H. pylori β-clamp and the structures show that they bind at the protein-protein interaction site as expected. In vivo studies showed only two molecules, 5-chloroisatin, and 3,4-difluorobenzamide inhibited the growth of the pylori with MIC values in micro molar range, which is better than the inhibitory effect of the same drugs on E. coli. Therefore, the evaluation of such drugs against H. pylori may explore the possibility to use to generate species-specific pharmacophore for development of new drugs against H. pylori.
      Citation: Antibiotics
      PubDate: 2018-01-11
      DOI: 10.3390/antibiotics7010005
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 6: Reevaluation of the Acute Cystitis Symptom
           Score, a Self-Reporting Questionnaire. Part I. Development, Diagnosis and
           Differential Diagnosis

    • Authors: Jakhongir Alidjanov, Kurt Naber, Ulugbek Abdufattaev, Adrian Pilatz, Florian Wagenlehner
      First page: 6
      Abstract: This study aimed to reevaluate the Acute Cystitis Symptom Score (ACSS). The ACSS is a simple and standardized self-reporting questionnaire for the diagnosis of acute uncomplicated cystitis (AC) assessing typical and differential symptoms, quality of life, and possible changes after therapy in female patients with AC. This paper includes literature research, development and evaluation of the ACSS, an 18-item self-reporting questionnaire including (a) six questions about “typical” symptoms of AC, (b) four questions regarding differential diagnoses, (c) three questions on quality of life, and (d) five questions on additional conditions that may affect therapy. The ACSS was evaluated in 228 women (mean age 31.49 ± 11.71 years) in the Russian and Uzbek languages. Measurements of reliability, validity, predictive ability, and responsiveness were performed. Cronbach’s alpha for ACSS was 0.89, split-half reliability was 0.76 and 0.79 for first and second halves, and the correlation between them was 0.87. Mann-Whitney U test revealed a significant difference in scores of the “typical” symptoms between patients and controls (10.50 vs. 2.07, p < 0.001). The optimal threshold score was 6 points, with a 94% sensitivity and 90% specificity to predict AC. The “typical” symptom score decreased significantly when comparing before and after therapy (10.4 and 2.5, p < 0.001). The reevaluated Russian and Uzbek ACSS are accurate enough and can be recommended for clinical studies and practice for initial diagnosis and monitoring the process of the treatment of AC in women. Evaluation in German, UK English, and Hungarian languages was also performed and in other languages evaluation of the ACSS is in progress
      Citation: Antibiotics
      PubDate: 2018-01-15
      DOI: 10.3390/antibiotics7010006
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 7: Acknowledgement to Reviewers of Antibiotics
           in 2017

    • Authors: Antibiotics Editorial Office
      First page: 7
      Abstract: Peer review is an essential part in the publication process, ensuring that Antibiotics maintains high quality standards for its published papers.[...]
      Citation: Antibiotics
      PubDate: 2018-01-25
      DOI: 10.3390/antibiotics7010007
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 8: Phage-Bacterial Dynamics with Spatial
           Structure: Self Organization around Phage Sinks Can Promote Increased Cell
           Densities

    • Authors: James Bull, Kelly Christensen, Carly Scott, Benjamin Jack, Cameron Crandall, Stephen Krone
      First page: 8
      Abstract: Bacteria growing on surfaces appear to be profoundly more resistant to control by lytic bacteriophages than do the same cells grown in liquid. Here, we use simulation models to investigate whether spatial structure per se can account for this increased cell density in the presence of phages. A measure is derived for comparing cell densities between growth in spatially structured environments versus well mixed environments (known as mass action). Maintenance of sensitive cells requires some form of phage death; we invoke death mechanisms that are spatially fixed, as if produced by cells. Spatially structured phage death provides cells with a means of protection that can boost cell densities an order of magnitude above that attained under mass action, although the effect is sometimes in the opposite direction. Phage and bacteria self organize into separate refuges, and spatial structure operates so that the phage progeny from a single burst do not have independent fates (as they do with mass action). Phage incur a high loss when invading protected areas that have high cell densities, resulting in greater protection for the cells. By the same metric, mass action dynamics either show no sustained bacterial elevation or oscillate between states of low and high cell densities and an elevated average. The elevated cell densities observed in models with spatial structure do not approach the empirically observed increased density of cells in structured environments with phages (which can be many orders of magnitude), so the empirical phenomenon likely requires additional mechanisms than those analyzed here.
      Citation: Antibiotics
      PubDate: 2018-01-29
      DOI: 10.3390/antibiotics7010008
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 9: Use of a Regression Model to Study
           Host-Genomic Determinants of Phage Susceptibility in MRSA

    • Authors: Henrike Zschach, Mette Larsen, Henrik Hasman, Henrik Westh, Morten Nielsen, Ryszard Międzybrodzki, Ewa Jończyk-Matysiak, Beata Weber-Dąbrowska, Andrzej Górski
      First page: 9
      Abstract: Staphylococcus aureus is a major agent of nosocomial infections. Especially in methicillin-resistant strains, conventional treatment options are limited and expensive, which has fueled a growing interest in phage therapy approaches. We have tested the susceptibility of 207 clinical S. aureus strains to 12 (nine monovalent) different therapeutic phage preparations and subsequently employed linear regression models to estimate the influence of individual host gene families on resistance to phages. Specifically, we used a two-step regression model setup with a preselection step based on gene family enrichment. We show that our models are robust and capture the data’s underlying signal by comparing their performance to that of models build on randomized data. In doing so, we have identified 167 gene families that govern phage resistance in our strain set and performed functional analysis on them. This revealed genes of possible prophage or mobile genetic element origin, along with genes involved in restriction-modification and transcription regulators, though the majority were genes of unknown function. This study is a step in the direction of understanding the intricate host-phage relationship in this important pathogen with the outlook to targeted phage therapy applications.
      Citation: Antibiotics
      PubDate: 2018-01-29
      DOI: 10.3390/antibiotics7010009
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 10: Assessing the Knowledge, Attitudes and
           Behaviors of Human and Animal Health Students towards Antibiotic Use and
           Resistance: A Pilot Cross-Sectional Study in the UK

    • Authors: Oliver Dyar, Holly Hills, Lara-Turiya Seitz, Alex Perry, Diane Ashiru-Oredope
      First page: 10
      Abstract: The Global Action Plan on Antimicrobial Resistance highlights the importance of training all healthcare professionals. No study has assessed patterns of students’ knowledge, attitudes and practices concerning antibiotic use simultaneously across different healthcare course types. We conducted a cross-sectional multi-center survey among UK students. The survey was advertised through local survey coordinators at 25 universities. The online survey was accessible from 10th October to 17th November 2016 (before European Antibiotic Awareness Day). A total of 255 students from 25 universities participated, including students on medicine, pharmacy, nursing, physician associate, dentistry and veterinary medicine courses. Antibiotic resistance was considered to be a more important global challenge than climate change, obesity or food security (p < 0.001). Most students (95%) believed that antibiotic resistance will be a problem for their future practice, but fewer (69%) thought that the antibiotics they will prescribe, administer or dispense will contribute to the problem. A fifth of students felt they had sufficient knowledge of antibiotic use for their future work. Our exploratory study suggests that UK human and animal healthcare students are aware of the importance of antibiotic resistance, but many still have certain misconceptions. Campaigns and improved educational efforts applying behavioral insights methodology could address these.
      Citation: Antibiotics
      PubDate: 2018-01-30
      DOI: 10.3390/antibiotics7010010
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 11: Survey of Nonprescription Medication and
           Antibiotic Use in Patients with Stevens-Johnson Syndrome, Toxic Epidermal
           Necrolysis, and Overlap Syndrome

    • Authors: Katherine Sullivan, Meghan Jeffres, Robert Dellavalle, Robert Valuck, Heather Anderson
      First page: 11
      Abstract: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap syndrome (SJS-TEN) are rare, serious skin and mucosa break-down conditions frequently associated with antibiotic use. The role of nonprescription medications alone, or in combination with antibiotics in triggering SJS/TEN, is largely unknown. This study summarized data collected from patient surveys about nonprescription and antibiotic use prior to a SJS/TEN diagnosis. The survey was administered online to members of the U.S. SJS Foundation who had been diagnosed with SJS/TEN or were the parent of a child who had been diagnosed with SJS/TEN. Respondents were asked about nonprescription medications taken within the year before diagnosis, and the approximate point in time before diagnosis that they had taken them. They were also asked about specific prescription medications, including antibiotics, that they took before diagnosis. An estimated 4500 patients received an invitation to complete the survey. 251 patients completed it, resulting in a response rate of 5.6%. The mean age of respondents was 43 years (SD (standard deviation) = 17.3) and 70% were female. 32.3% of respondents indicated that a prescription antibiotic triggered their reaction. 14.1% indicated a nonprescription medication had triggered their SJS/TEN, and 18.1% said a nonprescription medication may have triggered their SJS/TEN. 85.5% of respondents said they took a nonprescription medication within three months of their SJS/TEN diagnosis. Of those respondents who reported that an antibiotic triggered their SJS/TEN, 35.2% reported taking a nonprescription medication within the three months prior to their diagnosis. This survey captured valuable information about nonprescription and antibiotic use in SJS/TEN patients. It is important for future studies to estimate the impact of antibiotics on SJS/TEN, and account for nonprescription medication use in that relationship.
      Citation: Antibiotics
      PubDate: 2018-02-01
      DOI: 10.3390/antibiotics7010011
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 12: Diversification of Secondary Metabolite
           Biosynthetic Gene Clusters Coincides with Lineage Divergence in
           Streptomyces

    • Authors: Mallory Choudoir, Charles Pepe-Ranney, Daniel Buckley
      First page: 12
      Abstract: We have identified Streptomyces sister-taxa which share a recent common ancestor and nearly identical small subunit (SSU) rRNA gene sequences, but inhabit distinct geographic ranges demarcated by latitude and have sufficient genomic divergence to represent distinct species. Here, we explore the evolutionary dynamics of secondary metabolite biosynthetic gene clusters (SMGCs) following lineage divergence of these sister-taxa. These sister-taxa strains contained 310 distinct SMGCs belonging to 22 different gene cluster classes. While there was broad conservation of these 22 gene cluster classes among the genomes analyzed, each individual genome harbored a different number of gene clusters within each class. A total of nine SMGCs were conserved across nearly all strains, but the majority (57%) of SMGCs were strain-specific. We show that while each individual genome has a unique combination of SMGCs, this diversity displays lineage-level modularity. Overall, the northern-derived (NDR) clade had more SMGCs than the southern-derived (SDR) clade (40.7 ± 3.9 and 33.8 ± 3.9, mean and S.D., respectively). This difference in SMGC content corresponded with differences in the number of predicted open reading frames (ORFs) per genome (7775 ± 196 and 7093 ± 205, mean and S.D., respectively) such that the ratio of SMGC:ORF did not differ between sister-taxa genomes. We show that changes in SMGC diversity between the sister-taxa were driven primarily by gene acquisition and deletion events, and these changes were associated with an overall change in genome size which accompanied lineage divergence.
      Citation: Antibiotics
      PubDate: 2018-02-13
      DOI: 10.3390/antibiotics7010012
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 13: Efficacy of an Optimised Bacteriophage
           Cocktail to Clear Clostridium difficile in a Batch Fermentation Model

    • Authors: Janet Nale, Tamsin Redgwell, Andrew Millard, Martha Clokie
      First page: 13
      Abstract: Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimised 4-phage cocktail to clear cultures of a clinical ribotype 014/020 strain in fermentation vessels spiked with combined fecal slurries from four healthy volunteers. After 5 h, we observed ~6-log reductions in C. difficile abundance in the prophylaxis regimen and complete C. difficile eradication after 24 h following prophylactic or remedial regimens. Viability assays revealed that commensal enterococci, bifidobacteria, lactobacilli, total anaerobes, and enterobacteria were not affected by either regimens, but a ~2-log increase in the enterobacteria, lactobacilli, and total anaerobe abundance was seen in the phage-only-treated vessel compared to other treatments. The impact of the phage treatments on components of the microbiota was further assayed using metagenomic analysis. Together, our data supports the therapeutic application of our optimised phage cocktail to treat CDI. Also, the increase in specific commensals observed in the phage-treated control could prevent further colonisation of C. difficile, and thus provide protection from infection being able to establish.
      Citation: Antibiotics
      PubDate: 2018-02-13
      DOI: 10.3390/antibiotics7010013
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 14: Fragment-Based Discovery of Inhibitors of
           the Bacterial DnaG-SSB Interaction

    • Authors: Zorik Chilingaryan, Stephen Headey, Allen Lo, Zhi-Qiang Xu, Gottfried Otting, Nicholas Dixon, Martin Scanlon, Aaron Oakley
      First page: 14
      Abstract: In bacteria, the DnaG primase is responsible for synthesis of short RNA primers used to initiate chain extension by replicative DNA polymerase(s) during chromosomal replication. Among the proteins with which Escherichia coli DnaG interacts is the single-stranded DNA-binding protein, SSB. The C-terminal hexapeptide motif of SSB (DDDIPF; SSB-Ct) is highly conserved and is known to engage in essential interactions with many proteins in nucleic acid metabolism, including primase. Here, fragment-based screening by saturation-transfer difference nuclear magnetic resonance (STD-NMR) and surface plasmon resonance assays identified inhibitors of the primase/SSB-Ct interaction. Hits were shown to bind to the SSB-Ct-binding site using 15N–1H HSQC spectra. STD-NMR was used to demonstrate binding of one hit to other SSB-Ct binding partners, confirming the possibility of simultaneous inhibition of multiple protein/SSB interactions. The fragment molecules represent promising scaffolds on which to build to discover new antibacterial compounds.
      Citation: Antibiotics
      PubDate: 2018-02-22
      DOI: 10.3390/antibiotics7010014
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 15: Bacteriophage Interactions with Marine
           Pathogenic Vibrios: Implications for Phage Therapy

    • Authors: Panos Kalatzis, Daniel Castillo, Pantelis Katharios, Mathias Middelboe
      First page: 15
      Abstract: A global distribution in marine, brackish, and freshwater ecosystems, in combination with high abundances and biomass, make vibrios key players in aquatic environments, as well as important pathogens for humans and marine animals. Incidents of Vibrio-associated diseases (vibriosis) in marine aquaculture are being increasingly reported on a global scale, due to the fast growth of the industry over the past few decades years. The administration of antibiotics has been the most commonly applied therapy used to control vibriosis outbreaks, giving rise to concerns about development and spreading of antibiotic-resistant bacteria in the environment. Hence, the idea of using lytic bacteriophages as therapeutic agents against bacterial diseases has been revived during the last years. Bacteriophage therapy constitutes a promising alternative not only for treatment, but also for prevention of vibriosis in aquaculture. However, several scientific and technological challenges still need further investigation before reliable, reproducible treatments with commercial potential are available for the aquaculture industry. The potential and the challenges of phage-based alternatives to antibiotic treatment of vibriosis are addressed in this review.
      Citation: Antibiotics
      PubDate: 2018-02-24
      DOI: 10.3390/antibiotics7010015
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 16: Protective Effects of Bacteriophages
           against Aeromonas hydrophila Causing Motile Aeromonas Septicemia (MAS) in
           Striped Catfish

    • Authors: Tuan Son Le, Thi Hien Nguyen, Hong Phuong Vo, Van Cuong Doan, Hong Loc Nguyen, Minh Trung Tran, Trong Tuan Tran, Paul C. Southgate, D. İpek Kurtböke
      First page: 16
      Abstract: To determine the effectivity of bacteriophages in controlling the mass mortality of striped catfish (Pangasianodon hypophthalmus) due to infections caused by Aeromonas spp. in Vietnamese fish farms, bacteriophages against pathogenic Aeromonas hydrophila were isolated. A. hydrophila-phage 2 and A. hydrophila-phage 5 were successfully isolated from water samples from the Saigon River of Ho Chi Minh City, Vietnam. These phages, belonging to the Myoviridae family, were found to have broad activity spectra, even against the tested multiple-antibiotic-resistant Aeromonas isolates. The latent periods and burst size of phage 2 were 10 min and 213 PFU per infected host cell, respectively. The bacteriophages proved to be effective in inhibiting the growth of the Aeromonas spp. under laboratory conditions. Phage treatments applied to the pathogenic strains during infestation of catfish resulted in a significant improvement in the survival rates of the tested fishes, with up to 100% survival with MOI 100, compared to 18.3% survival observed in control experiments. These findings illustrate the potential for using phages as an effective bio-treatment method to control Motile Aeromonas Septicemia (MAS) in fish farms. This study provides further evidence towards the use of bacteriophages to effectively control disease in aquaculture operations.
      Citation: Antibiotics
      PubDate: 2018-02-25
      DOI: 10.3390/antibiotics7010016
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 17: Potential for Bacteriophage Endolysins to
           Supplement or Replace Antibiotics in Food Production and Clinical Care

    • Authors: Michael Love, Dinesh Bhandari, Renwick Dobson, Craig Billington
      First page: 17
      Abstract: There is growing concern about the emergence of bacterial strains showing resistance to all classes of antibiotics commonly used in human medicine. Despite the broad range of available antibiotics, bacterial resistance has been identified for every antimicrobial drug developed to date. Alarmingly, there is also an increasing prevalence of multidrug-resistant bacterial strains, rendering some patients effectively untreatable. Therefore, there is an urgent need to develop alternatives to conventional antibiotics for use in the treatment of both humans and food-producing animals. Bacteriophage-encoded lytic enzymes (endolysins), which degrade the cell wall of the bacterial host to release progeny virions, are potential alternatives to antibiotics. Preliminary studies show that endolysins can disrupt the cell wall when applied exogenously, though this has so far proven more effective in Gram-positive bacteria compared with Gram-negative bacteria. Their potential for development is furthered by the prospect of bioengineering, and aided by the modular domain structure of many endolysins, which separates the binding and catalytic activities into distinct subunits. These subunits can be rearranged to create novel, chimeric enzymes with optimized functionality. Furthermore, there is evidence that the development of resistance to these enzymes may be more difficult compared with conventional antibiotics due to their targeting of highly conserved bonds.
      Citation: Antibiotics
      PubDate: 2018-02-27
      DOI: 10.3390/antibiotics7010017
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 18: Efflux Activity Differentially Modulates
           the Levels of Isoniazid and Rifampicin Resistance among Multidrug
           Resistant and Monoresistant Mycobacterium tuberculosis Strains

    • Authors: Diana Machado, João Perdigão, Isabel Portugal, Marco Pieroni, Pedro Silva, Isabel Couto, Miguel Viveiros
      First page: 18
      Abstract: With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. The results demonstrated that all the M. tuberculosis clinical strains, susceptible or resistant, presented a faster, rapid, and non-specific efflux-mediated short-term response to drugs. The synergism assays demonstrated that the efflux inhibitors were more effective in reducing the resistance levels in the M/XDR strains than in the monoresistant strains. This indicated that M/XDR strains presented a more prolonged response to drugs mediated by efflux compared to the monoresistant strains, but both maintain it as a long-term stress response. This work shows that efflux activity modulates the levels of drug resistance between monoresistant and M/XDR M. tuberculosis clinical strains, allowing the bacteria to survive in the presence of noxious compounds.
      Citation: Antibiotics
      PubDate: 2018-03-03
      DOI: 10.3390/antibiotics7010018
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 19: Genetic Determinants of Tetracycline
           Resistance in Clinical Streptococcus pneumoniae Serotype 1 Isolates from
           Niger

    • Authors: Sani Ousmane, Bouli Diallo, Rasmata Ouedraogo
      First page: 19
      Abstract: Streptococcus pneumoniae serotype 1 is the first cause of pneumococcal meningitis Niger. To determine the underlying mechanism of resistance to tetracycline in serotype 1 Streptococcus pneumoniae, a collection of 37 isolates recovered from meningitis patients over the period of 2002 to 2009 in Niger were analyzed for drug susceptibility, and whole genome sequencing (WGS) was performed for molecular analyses. MIC level was determined for 31/37 (83.8%) isolates and allowed detection of full resistance (MIC = 8 µg) in 24/31 (77.4%) isolates. No resistance was found to macrolides and quinolones. Sequence-types deduced from WGS were ST217 (54.1%), ST303 (35.1%), ST2206 (5.4%), ST2839 (2.7%) and one undetermined ST (2.7%). All tetracycline resistant isolates carried a Tn5253 like element, which was found to be an association of two smaller transposons of Tn916 and Tn5252 families. No tet(O) and tet(Q) genes were detected. However, a tet(M) like sequence was identified in all Tn5253 positive strains and was found associated to Tn916 composite. Only one isolate was phenotypically resistant to chloramphenicol, wherein a chloramphenicol acetyl transferase (cat) gene sequence homologous to catpC194 from the Staphylococcus aureus plasmid pC194 was detected. In conclusion, clinical Streptococcus pneumoniae type 1 isolated during 2002 to 2009 meningitis surveillance in Niger were fully susceptible to macrolides and quinolones but highly resistant to tetracycline (77.4%) through acquisition of a defective Tn5253 like element composed of Tn5252 and Tn916 transposons. Of the 31 tested isolates, only one was exceptionally resistant to chloramphenicol and carried a Tn5253 transposon that contained cat gene sequence.
      Citation: Antibiotics
      PubDate: 2018-03-06
      DOI: 10.3390/antibiotics7010019
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 20: Biosynthesis of Rishirilide B

    • Authors: Philipp Schwarzer, Julia Wunsch-Palasis, Andreas Bechthold, Thomas Paululat
      First page: 20
      Abstract: Rishirilide B was isolated from Streptomyces rishiriensis and Streptomyces bottropensis on the basis of its inhibitory activity towards alpha-2-macroglobulin. The biosynthesis of rishirilide B was investigated by feeding experiments with different 13C labelled precursors using the heterologous host Streptomyces albus J1074::cos4 containing a cosmid encoding of the gene cluster responsible for rishirilide B production. NMR spectroscopic analysis of labelled compounds demonstrate that the tricyclic backbone of rishirilide B is a polyketide synthesized from nine acetate units. One of the acetate units is decarboxylated to give a methyl group. The origin of the starter unit was determined to be isobutyrate.
      Citation: Antibiotics
      PubDate: 2018-03-07
      DOI: 10.3390/antibiotics7010020
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 21: Protein Expression Modifications in
           Phage-Resistant Mutants of Aeromonas salmonicida after AS-A Phage
           Treatment

    • Authors: Catarina Moreirinha, Nádia Osório, Carla Pereira, Sara Simões, Ivonne Delgadillo, Adelaide Almeida
      First page: 21
      Abstract: The occurrence of infections by pathogenic bacteria is one of the main sources of financial loss for the aquaculture industry. This problem often cannot be solved with antibiotic treatment or vaccination. Phage therapy seems to be an alternative environmentally-friendly strategy to control infections. Recognizing the cellular modifications that bacteriophage therapy may cause to the host is essential in order to confirm microbial inactivation, while understanding the mechanisms that drive the development of phage-resistant strains. The aim of this work was to detect cellular modifications that occur after phage AS-A treatment in A. salmonicida, an important fish pathogen. Phage-resistant and susceptible cells were subjected to five successive streak-plating steps and analysed with infrared spectroscopy, a fast and powerful tool for cell study. The spectral differences of both populations were investigated and compared with a phage sensitivity profile, obtained through the spot test and efficiency of plating. Changes in protein associated peaks were found, and these results were corroborated by 1-D electrophoresis of intracellular proteins analysis and by phage sensitivity profiles. Phage AS-A treatment before the first streaking-plate step clearly affected the intracellular proteins expression levels of phage-resistant clones, altering the expression of distinct proteins during the subsequent five successive streak-plating steps, making these clones recover and be phenotypically more similar to the sensitive cells.
      Citation: Antibiotics
      PubDate: 2018-03-08
      DOI: 10.3390/antibiotics7010021
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 22: Potentially Important Therapeutic
           Interactions between Antibiotics, and a Specially Engineered Emulsion Drug
           Vehicle Containing Krill-Oil-Based Phospholipids and Omega-3 Fatty Acids

    • Authors: David Driscoll
      First page: 22
      Abstract: The incidence of antimicrobial resistance (AMR) worldwide is increasing as the pipeline for the development of new chemotherapeutic entities is decreasing. Clearly, overexposure to antibiotics, including excessive dosing, is a key factor that fuels AMR. In fact, most of the new antibacterial agents under development are derivatives of existing classes of antibiotics. Novel approaches involving unique antimicrobial combinations, targets, and/or delivery systems are under intense investigation. An innovative combination of active pharmaceutical ingredients (APIs) consisting of antimicrobial drug(s), krill-oil-based phospholipids, and omega-3 fatty acid triglycerides, that may extend the therapeutic viability of currently effective antibiotics, at least until new chemical entities are introduced, is described.
      Citation: Antibiotics
      PubDate: 2018-03-10
      DOI: 10.3390/antibiotics7010022
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 23: The Macromolecular Machines that Duplicate
           the Escherichia coli Chromosome as Targets for Drug Discovery

    • Authors: Jon Kaguni
      First page: 23
      Abstract: DNA replication is an essential process. Although the fundamental strategies to duplicate chromosomes are similar in all free-living organisms, the enzymes of the three domains of life that perform similar functions in DNA replication differ in amino acid sequence and their three-dimensional structures. Moreover, the respective proteins generally utilize different enzymatic mechanisms. Hence, the replication proteins that are highly conserved among bacterial species are attractive targets to develop novel antibiotics as the compounds are unlikely to demonstrate off-target effects. For those proteins that differ among bacteria, compounds that are species-specific may be found. Escherichia coli has been developed as a model system to study DNA replication, serving as a benchmark for comparison. This review summarizes the functions of individual E. coli proteins, and the compounds that inhibit them.
      Citation: Antibiotics
      PubDate: 2018-03-14
      DOI: 10.3390/antibiotics7010023
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 24: Parallel Colorimetric Quantification of
           Choline and Phosphocholine as a Method for Studying Choline Kinase
           Activity in Complex Mixtures

    • Authors: Tahl Zimmerman, Salam A. Ibrahim
      First page: 24
      Abstract: Choline kinase (Chok) is an enzyme found in eukaryotes and Gram-positive bacteria. Chok catalyzes the production of phosphocholine from choline and ATP. This enzyme has been validated as a drug target in Streptococcus pneumonia, but the role Chok enzymatic activity plays in bacterial cell growth and division is not well understood. Phosphocholine production by Chok and its attenuation by inhibitors in the context of complex samples such as cell extracts can currently be quantified by several methods. These include choline depletion measurements, radioactive methods, mass-spectrometry, and nuclear magnetic resonance. The first does not measure phosphocholine directly, the second requires elaborate safety procedures, and the third and fourth require significant capital investments and technical expertise. For these reasons, a less expensive, higher throughput, more easily accessible assay is needed to facilitate further study in Gram-positive Choks. Here, we present the development of a triiodide/activated charcoal/molybdenum blue system for detecting and quantifying choline and phosphocholine in parallel. We demonstrate that this system can reliably quantify changes in choline and phosphocholine concentrations over time in Chok enzymatic assays using cell extracts as the source of the enzyme. This is an easily accessible, convenient, robust, and economical method for studying Chok activity in complex samples. The triiodide/activated charcoal/molybdenum blue system opens new doors into the study choline kinase in Gram-positive pathogens.
      Citation: Antibiotics
      PubDate: 2018-03-17
      DOI: 10.3390/antibiotics7010024
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 25: Novel Aspects of Polynucleotide
           Phosphorylase Function in Streptomyces

    • Authors: George Jones
      First page: 25
      Abstract: Polynucleotide phosphorylase (PNPase) is a 3′–5′-exoribnuclease that is found in most bacteria and in some eukaryotic organelles. The enzyme plays a key role in RNA decay in these systems. PNPase structure and function have been studied extensively in Escherichia coli, but there are several important aspects of PNPase function in Streptomyces that differ from what is observed in E. coli and other bacterial genera. This review highlights several of those differences: (1) the organization and expression of the PNPase gene in Streptomyces; (2) the possible function of PNPase as an RNA 3′-polyribonucleotide polymerase in Streptomyces; (3) the function of PNPase as both an exoribonuclease and as an RNA 3′-polyribonucleotide polymerase in Streptomyces; (4) the function of (p)ppGpp as a PNPase effector in Streptomyces. The review concludes with a consideration of a number of unanswered questions regarding the function of Streptomyces PNPase, which can be examined experimentally.
      Citation: Antibiotics
      PubDate: 2018-03-18
      DOI: 10.3390/antibiotics7010025
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 26: Geographic Variation in Antibiotic
           Consumption—Is It Due to Doctors’ Prescribing or Patients’
           Consulting'

    • Authors: Marte Walle-Hansen, Sigurd Høye
      First page: 26
      Abstract: Antibiotic consumption varies greatly between Norwegian municipalities. We examine whether this variation is associated with inhabitants’ consultation rates or general practitioners’ (GP) prescription rates. Our study comprises consultations and antibiotic prescriptions for respiratory tract infections (RTIs) in general practice in all Norwegian municipalities with over 5000 inhabitants in 2014. Data was collected from The Norwegian Prescription Database, The Directorate of Health’s system for control and payment of health reimbursements registry and Norway Statistics. Consultation rates and prescription rates were categorised in age- and gender specific quintiles and the effect on antibiotic consumption was analysed using a Poisson regression model. We found that inhabitants with RTIs received 42% more prescriptions if they belonged to a municipality with high consultation rates compared to low consultation rates [incidence rate ratio (IRR) 1.42 (95% CI 1.41–1.44)] and 48% more prescriptions if they belonged to a municipality with high prescription rates versus low prescription rates [IRR 1.48 (95% KI 1.47–1.50)]. Our results demonstrate that inhabitants’ consultation rates and GPs’ prescription rates have about equal impact on the number of RTI antibiotics prescribed at municipality level. These findings highlight the importance of interventions targeting patients as well as doctors in efforts to reduce unnecessary antibiotic consumption.
      Citation: Antibiotics
      PubDate: 2018-03-20
      DOI: 10.3390/antibiotics7010026
      Issue No: Vol. 7, No. 1 (2018)
       
  • Antibiotics, Vol. 7, Pages 1: Sperm Quality during Storage Is Not Affected
           by the Presence of Antibiotics in EquiPlus Semen Extender but Is Improved
           by Single Layer Centrifugation

    • Authors: Ziyad Al-Kass, Joachim Spergser, Christine Aurich, Juliane Kuhl, Kathrin Schmidt, Anders Johannisson, Jane Morrell
      First page: 1
      Abstract: Contamination of semen with bacteria arises during semen collection and handling. This bacterial contamination is typically controlled by adding antibiotics to semen extenders but intensive usage of antibiotics can lead to the development of bacterial resistance and may be detrimental to sperm quality. The objective of this study was to determine the effects of antibiotics in a semen extender on sperm quality and to investigate the effects of removal of bacteria by modified Single Layer Centrifugation (MSLC) through a colloid. Semen was collected from six adult pony stallions (three ejaculates per male). Aliquots of extended semen were used for MSLC with Equicoll, resulting in four treatment groups: control and MSLC in extender with antibiotics (CA and SA, respectively); control and MSLC in extender without antibiotics (CW and SW, respectively). Sperm motility, membrane integrity, mitochondrial membrane potential and chromatin integrity were evaluated daily by computer-assisted sperm analysis (CASA) and flow cytometry. There were no differences in sperm quality between CA and CW, or between SA and SW, although progressive motility was negatively correlated to total bacterial counts at 0 h. However, MSLC groups showed higher mean total motility (P < 0.001), progressive motility (P < 0.05), membrane integrity (P < 0.0001) and mitochondrial membrane potential (P < 0.05), as well as better chromatin integrity (P < 0.05), than controls. Sperm quality remained higher in the MSLC groups than controls throughout storage. These results indicate that sperm quality was not adversely affected by the presence of antibiotics but was improved considerably by MSLC.
      Citation: Antibiotics
      PubDate: 2017-12-21
      DOI: 10.3390/antibiotics7010001
      Issue No: Vol. 7, No. 1 (2017)
       
  • Antibiotics, Vol. 7, Pages 2: Evidence for Anti-Pseudogymnoascus
           destructans (Pd) Activity of Propolis

    • Authors: Soumya Ghosh, Robyn McArthur, Zhi Guo, Rory McKerchar, Kingsley Donkor, Jianping Xu, Naowarat Cheeptham
      First page: 2
      Abstract: White-nose syndrome (WNS) in bats, caused by Pseudogymnoascus destructans (Pd), is a cutaneous infection that has devastated North American bat populations since 2007. At present, there is no effective method for controlling this disease. Here, we evaluated the effect of propolis against Pd in vitro. Using Sabouraud dextrose agar (SDA) medium, approximately 1.7 × 107 conidia spores of the Pd strain M3906-2/mL were spread on each plate and grown to form a consistent lawn. A Kirby–Bauer disk diffusion assay was employed using different concentrations of propolis (1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%), in plates incubated at 8 °C and 15 °C. At 8 °C and 15 °C, as the concentration of propolis increased, there was an increasing zone of inhibition (ZOI), reaching the highest degree at 10% and 25% concentrations, respectively. A germule suppression assay showed a similar effect on Pd conidia germination. A MALDI-TOF-MS analysis of propolis revealed multiple constituents with a potential anti-Pd activity, including cinnamic acid, p-coumaric acid, and dihydrochalcones, which could be further tested for their individual effects. Our study suggests that propolis or its individual constituents might be suitable products against Pd.
      Citation: Antibiotics
      PubDate: 2017-12-21
      DOI: 10.3390/antibiotics7010002
      Issue No: Vol. 7, No. 1 (2017)
       
  • Antibiotics, Vol. 7, Pages 3: Establishing a System for Testing
           Replication Inhibition of the Vibrio cholerae Secondary Chromosome in
           Escherichia coli

    • Authors: Nadine Schallopp, Sarah Milbredt, Theodor Sperlea, Franziska Kemter, Matthias Bruhn, Daniel Schindler, Torsten Waldminghaus
      First page: 3
      Abstract: Regulators of DNA replication in bacteria are an attractive target for new antibiotics, as not only is replication essential for cell viability, but its underlying mechanisms also differ from those operating in eukaryotes. The genetic information of most bacteria is encoded on a single chromosome, but about 10% of species carry a split genome spanning multiple chromosomes. The best studied bacterium in this context is the human pathogen Vibrio cholerae, with a primary chromosome (Chr1) of 3 M bps, and a secondary one (Chr2) of about 1 M bps. Replication of Chr2 is under control of a unique mechanism, presenting a potential target in the development of V. cholerae-specific antibiotics. A common challenge in such endeavors is whether the effects of candidate chemicals can be focused on specific mechanisms, such as DNA replication. To test the specificity of antimicrobial substances independent of other features of the V. cholerae cell for the replication mechanism of the V. cholerae secondary chromosome, we establish the replication machinery in the heterologous E. coli system. We characterize an E. coli strain in which chromosomal replication is driven by the replication origin of V. cholerae Chr2. Surprisingly, the E. coli ori2 strain was not inhibited by vibrepin, previously found to inhibit ori2-based replication.
      Citation: Antibiotics
      PubDate: 2017-12-23
      DOI: 10.3390/antibiotics7010003
      Issue No: Vol. 7, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 20: Choline Kinase, A Novel Drug Target for the
           Inhibition of Streptococcus pneumoniae

    • Authors: Tahl Zimmerman, Salam Ibrahim
      First page: 20
      Abstract: Gram-positive pathogens, such as Streptococcus pneumoniae, can have deleterious effects on both human and animal health. Antibiotics and antimicrobials have been developed to treat infections caused by such pathogens and to prevent food contamination. However, these strategies have been increasingly thwarted by the emergence of resistant bacteria strains. Thus, new methods for controlling Gram-positive pathogen growth need to be continuously developed. Choline analogs, such as Hemicholinium-3 (HC-3), have been shown to be useful in blocking cell division in eukaryotic cells through the inhibition of choline kinase, an enzyme which catalyzes the production of phosphocholine from choline and ATP. In some Gram-positive pathogens, choline kinase is an important enzyme in the production of the cell wall element, lipoteichoic acid. However, it is not known if inhibiting this enzyme has any effect on cell division in Gram-positive bacteria. Using the R6 strain as a model, we tested the ability of HC-3 to block the activity of choline kinase in S. pneumoniae and inhibit cell growth. Mass-spectrometry measurements of crude extracts revealed that HC-3 blocked choline kinase activity. Turbidity measurements and population counts showed that HC-3 inhibited cell growth. Competition assays with choline suggested that HC-3 also blocked choline transporters. Western blots showed that lipoteichoic acid production was blocked in the presence of HC-3, and autolytic assays showed that this decrease in lipoteichoic acids caused cells to be more resistant to autolysis. Scanning electron microscopy revealed that HC-3 distorted the cell wall. This study thus establishes choline kinase as a novel drug target for S. pneumoniae.
      Citation: Antibiotics
      PubDate: 2017-09-25
      DOI: 10.3390/antibiotics6040020
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 21: Probiotics for the Prevention of
           Antibiotic-Associated Diarrhea in Outpatients—A Systematic Review and
           Meta-Analysis

    • Authors: Sara Blaabjerg, Daniel Artzi, Rune Aabenhus
      First page: 21
      Abstract: A common adverse effect of antibiotic use is diarrhea. Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The objective of this systematic review was to assess the benefits and harms of probiotics used for the prevention of AAD in an outpatient setting. A search of the PubMed database was conducted and yielded a total of 17 RCTs with 3631 participants to be included in the review. A meta-analysis was conducted for the primary outcome: the incidence of AAD. The pooled results found that AAD was present in 8.0% of the probiotic group compared to 17.7% in the control group (RR 0.49, 95% CI 0.36 to 0.66; I2 = 58%), and the species-specific results were similar regarding the probiotic strains L. rhamnosus GG and S. boulardii. However, the overall quality of the included studies was moderate. A meta-analysis of the ten trials reporting adverse events demonstrated no statistically significant differences in the incidence of adverse events between the intervention and control group (RD 0.00, 95% CI −0.02 to 0.02, 2.363 participants). The results suggests that probiotic use may be beneficial in the prevention of AAD among outpatients. Furthermore, the use of probiotics appears safe.
      Citation: Antibiotics
      PubDate: 2017-10-12
      DOI: 10.3390/antibiotics6040021
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 22: Antibiotic Prescribing for Uncomplicated
           Acute Bronchitis Is Highest in Younger Adults

    • Authors: Larissa Grigoryan, Roger Zoorob, Jesal Shah, Haijun Wang, Monisha Arya, Barbara W. Trautner
      First page: 22
      Abstract: Reducing inappropriate antibiotic prescribing is currently a global health priority. Current guidelines recommend against antibiotic treatment for acute uncomplicated bronchitis. We studied antibiotic prescribing patterns for uncomplicated acute bronchitis and identified predictors of inappropriate antibiotic prescribing. We used the Epic Clarity database (electronic medical record system) to identify all adult patients with acute bronchitis in family medicine clinics from 2011 to 2016. We excluded factors that could justify antibiotic use, such as suspected pneumonia, COPD or immunocompromising conditions. Of the 3616 visits for uncomplicated acute bronchitis, 2244 (62.1%) resulted in antibiotic treatment. The rates of antibiotic prescribing were similar across the years, p value for trend = 0.07. Antibiotics were most frequently prescribed in the age group of 18–39 years (66.9%), followed by the age group of 65 years and above (59.0%), and the age group of 40–64 years (58.7%), p value < 0.001. Macrolides were significantly more likely to be prescribed for younger adults, while fluoroquinolones were more likely to be prescribed for patients 65 years or older. Duration of antibiotic use was significantly longer in older adults. Sex and race were not associated with antibiotic prescribing. Our findings highlight the urgent need to reduce inappropriate antibiotic use for uncomplicated acute bronchitis, particularly in younger adults.
      Citation: Antibiotics
      PubDate: 2017-10-27
      DOI: 10.3390/antibiotics6040022
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 23: Exploring Patient Awareness and Perceptions
           of the Appropriate Use of Antibiotics: A Mixed-Methods Study

    • Authors: Marion Davis, Tsai-Ling Liu, Yhenneko Taylor, Lisa Davidson, Monica Schmid, Traci Yates, Janice Scotton, Melanie Spencer
      First page: 23
      Abstract: In the outpatient setting, estimates suggest that 30% of the antibiotics prescribed are unnecessary. This study explores patient knowledge and awareness of appropriate use of antibiotics and expectations regarding how antibiotics are used for their treatment in outpatient settings. A survey was administered to a convenience sample of patients, parents, and caregivers (n = 190) at seven primary care clinics and two urgent care locations. Fisher’s exact tests compared results by patient characteristics. Although 89% of patients correctly believed that antibiotics work well for treating infections from bacteria, 53% incorrectly believed that antibiotics work well for treating viral infections. Patients who incorrectly believed that antibiotics work well for treating viral infections were more than twice as likely to expect a provider to give them an antibiotic when they have a cough or common cold. Patients who completed the survey also participated in semi-structured interviews (n = 4), which were analyzed using thematic analysis. Patients reported experiencing confusion about which illnesses may be treated by antibiotics and unclear communication from clinicians about the appropriate use of antibiotics. Development of easy to understand patient educational materials can help address patients’ incorrect perceptions of appropriate antibiotic use and facilitate patient-provider communication.
      Citation: Antibiotics
      PubDate: 2017-10-31
      DOI: 10.3390/antibiotics6040023
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 24: Fosfomycin: Pharmacological, Clinical and
           Future Perspectives

    • Authors: Anneke Corinne Dijkmans, Natalia Veneranda Ortiz Zacarías, Jacobus Burggraaf, Johan Willem Mouton, Erik Wilms, Cees van Nieuwkoop, Daniel Johannes Touw, Jasper Stevens, Ingrid Maria Catharina Kamerling
      First page: 24
      Abstract: Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.
      Citation: Antibiotics
      PubDate: 2017-10-31
      DOI: 10.3390/antibiotics6040024
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 25: Identification and Antimicrobial
           Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical
           Microbiology'

    • Authors: Márió Gajdács, Gabriella Spengler, Edit Urbán
      First page: 25
      Abstract: Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria.
      Citation: Antibiotics
      PubDate: 2017-11-07
      DOI: 10.3390/antibiotics6040025
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 26: Ubiquitous Nature of Fluoroquinolones: The
           Oscillation between Antibacterial and Anticancer Activities

    • Authors: Temilolu Idowu, Frank Schweizer
      First page: 26
      Abstract: Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds.
      Citation: Antibiotics
      PubDate: 2017-11-07
      DOI: 10.3390/antibiotics6040026
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 27: Bacteriophages in the Dairy Environment:
           From Enemies to Allies

    • Authors: Lucía Fernández, Susana Escobedo, Diana Gutiérrez, Silvia Portilla, Beatriz Martínez, Pilar García, Ana Rodríguez
      First page: 27
      Abstract: The history of dairy farming goes back thousands of years, evolving from a traditional small-scale production to the industrialized manufacturing of fermented dairy products. Commercialization of milk and its derived products has been very important not only as a source of nourishment but also as an economic resource. However, the dairy industry has encountered several problems that have to be overcome to ensure the quality and safety of the final products, as well as to avoid economic losses. Within this context, it is interesting to highlight the role played by bacteriophages, or phages, viruses that infect bacteria. Indeed, bacteriophages were originally regarded as a nuisance, being responsible for fermentation failure and economic losses when infecting lactic acid bacteria, but are now considered promising antimicrobials to fight milk-borne pathogens without contributing to the increase in antibiotic resistance.
      Citation: Antibiotics
      PubDate: 2017-11-08
      DOI: 10.3390/antibiotics6040027
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 28: Interplay between Colistin Resistance,
           Virulence and Fitness in Acinetobacter baumannii

    • Authors: Gabriela Da Silva, Sara Domingues
      First page: 28
      Abstract: Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM. LPS modification prevents the binding of polymyxin to the bacterial surface and may lead to alterations in bacterial virulence. Antimicrobial pressure drives the evolution of antimicrobial resistance and resistance is often associated with a reduced bacterial fitness. Therefore, the alterations in LPS may induce changes in the fitness of A. baumannii. However, compensatory mutations in clinical A. baumannii may ameliorate the cost of resistance and may play an important role in the dissemination of colistin-resistant A. baumannii isolates. The focus of this review is to summarize the colistin resistance mechanisms, and understand their impact on the fitness and virulence of bacteria and on the dissemination of colistin-resistant A. baumannii strains.
      Citation: Antibiotics
      PubDate: 2017-11-21
      DOI: 10.3390/antibiotics6040028
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 29: Activity In Vitro of Clotrimazole against
           Canine Methicillin-Resistant and Susceptible Staphylococcus
           pseudintermedius

    • Authors: Sian-Marie Frosini, Ross Bond
      First page: 29
      Abstract: Emergence of multidrug-resistance in Staphylococcus pseudintermedius (SP) has increased interest in topical therapy as an alternative to systemic antibiotics in canine pyoderma. The antifungal imidazole, clotrimazole, is contained in numerous licensed canine ear preparations. Its in vitro activity against SP has not been evaluated, although previous studies have shown that the related imidazole, miconazole, has significant anti-staphylococcal efficacy. We therefore determined minimum inhibitory concentrations (MICs) of clotrimazole amongst 50 SP isolates (25 methicillin-resistant [MR]SP and susceptible [MS]SP) collected from dogs in Germany during 2010–2011 using an agar dilution method (CLSI VET01-A4). MICs amongst MRSP and MSSP were comparable (MIC50 and MIC90 = 1mg/L for both groups, p = 0.317); overall, 49 isolates had MIC = 1 mg/L and one had MIC = 0.5 mg/L. The relatively low MICs obtained in this study are likely to be exceeded by topical therapy and thus further clinical evaluation of clotrimazole use in canine superficial pyoderma and otitis externa caused by MRSP and MSSP is now warranted.
      Citation: Antibiotics
      PubDate: 2017-11-22
      DOI: 10.3390/antibiotics6040029
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 30: Establishing Genotype-to-Phenotype
           Relationships in Bacteria Causing Hospital-Acquired Pneumonia: A Prelude
           to the Application of Clinical Metagenomics

    • Authors: Etienne Ruppé, Abdessalam Cherkaoui, Vladimir Lazarevic, Stéphane Emonet, Jacques Schrenzel
      First page: 30
      Abstract: Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly, based on the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.
      Citation: Antibiotics
      PubDate: 2017-11-29
      DOI: 10.3390/antibiotics6040030
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 31: Antimicrobial Activity of Bee Venom and
           Melittin against Borrelia burgdorferi

    • Authors: Kayla Socarras, Priyanka Theophilus, Jason Torres, Khusali Gupta, Eva Sapi
      First page: 31
      Abstract: Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use.
      Citation: Antibiotics
      PubDate: 2017-11-29
      DOI: 10.3390/antibiotics6040031
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 32: Is Genetic Mobilization Considered When
           Using Bacteriophages in Antimicrobial Therapy'

    • Authors: Lorena Rodríguez-Rubio, Joan Jofre, Maite Muniesa
      First page: 32
      Abstract: The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes.
      Citation: Antibiotics
      PubDate: 2017-12-05
      DOI: 10.3390/antibiotics6040032
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 33: Dual Regulation of the Small RNA MicC and
           the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia
           coli

    • Authors: Sushovan Dam, Jean-Marie Pagès, Muriel Masi
      First page: 33
      Abstract: Antibiotic resistant Gram-negative bacteria are a serious threat for public health. The permeation of antibiotics through their outer membrane is largely dependent on porin, changes in which cause reduced drug uptake and efficacy. Escherichia coli produces two major porins, OmpF and OmpC. MicF and MicC are small non-coding RNAs (sRNAs) that modulate the expression of OmpF and OmpC, respectively. In this work, we investigated factors that lead to increased production of MicC. micC promoter region was fused to lacZ, and the reporter plasmid was transformed into E. coli MC4100 and derivative mutants. The response of micC–lacZ to antimicrobials was measured during growth over a 6 h time period. The data showed that the expression of micC was increased in the presence of β-lactam antibiotics and in an rpoE depleted mutant. Interestingly, the same conditions enhanced the activity of an ompN–lacZ fusion, suggesting a dual transcriptional regulation of micC and the quiescent adjacent ompN. Increased levels of OmpN in the presence of sub-inhibitory concentrations of chemicals could not be confirmed by Western blot analysis, except when analyzed in the absence of the sigma factor σE. We suggest that the MicC sRNA acts together with the σE envelope stress response pathway to control the OmpC/N levels in response to β-lactam antibiotics.
      Citation: Antibiotics
      PubDate: 2017-12-06
      DOI: 10.3390/antibiotics6040033
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 34: Evaluation of Antibiotic Residues in Raw
           Meat Using Different Analytical Methods

    • Authors: Tsepo Ramatla, Lubanza Ngoma, Modupeade Adetunji, Mulunda Mwanza
      First page: 34
      Abstract: Antibiotic residue in meat is a serious public health concern due to its harmful effects on consumer health. This study aimed at estimating the residue levels of four commonly used antibiotics in meat samples using three analytical methods (ELISA, TLC and HPLC). A total of 150 samples of raw meat from sales points were analysed for ciprofloxacin, streptomycin, tetracycline, and sulphanilamide residues. Overall, ELISA analysis showed that 56, 34, 18, and 25.3% of the samples tested positive for ciprofloxacin, streptomycin, sulphanilamide and tetracycline residues respectively while TLC and HPLC detected 21.4, 29.4, 92.5, and 14.6%, and 8.3, 41.1, 88.8, and 14.6% of the samples as containing the residues, with ciprofloxacin and sulphanilamide having the lowest and highest occurrence, respectively. Furthermore, the concentrations of antibiotic residues were in the ranges of 19.8–92.8, 26.6–489.1, 14.2–1280.8, and 42.6–355.6 μg/kg with ELISA, while HPLC detected concentration ranges of 20.7–82.1, 41.8–320.8, 65.2–952.2 and 32.8–95.6 μg/kg for sulphanilamide, tetracycline, streptomycin, and ciprofloxacin, respectively. Mean ciprofloxacin and streptomycin residue levels were above the Codex/SA MRL recommended limit, while 3% of the samples contained multidrug residues. Although some of the mean residues levels were below the permissible limits, the co-occurrence of multidrug residues in some of the samples calls for concern.
      Citation: Antibiotics
      PubDate: 2017-12-07
      DOI: 10.3390/antibiotics6040034
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 35: Nisin in Combination with Cinnamaldehyde
           and EDTA to Control Growth of Escherichia coli Strains of Swine Origin

    • Authors: Des Field, Inès Baghou, Mary Rea, Gillian Gardiner, R. Ross, Colin Hill
      First page: 35
      Abstract: Post-weaning diarrhoea (PWD) due to enterotoxigenic Escherichia coli (ETEC) is an economically important disease in pig production worldwide. Although antibiotics have contributed significantly to mitigate the economic losses caused by PWD, there is major concern over the increased incidence of antimicrobial resistance among bacteria isolated from pigs. Consequently, suitable alternatives that are safe and effective are urgently required. Many naturally occurring compounds, including the antimicrobial peptide nisin and a number of plant essential oils, have been widely studied and are reported to be effective as antimicrobial agents against pathogenic microorganisms. Here, we evaluate the potential of nisin in combination with the essential oil cinnamaldehyde and ethylenediaminetetraacetic acid (EDTA) to control the growth of E. coli strains of swine origin including two characterized as ETEC. The results reveal that the use of nisin (10 μM) with low concentrations of trans-cinnamaldehyde (125 μg/mL) and EDTA (0.25–2%) resulted in extended lag phases of growth compared to when either antimicrobial is used alone. Further analysis through kill curves revealed that an approximate 1-log reduction in E. coli cell counts was observed against the majority of targets tested following 3 h incubation. These results highlight the potential benefits of combining the natural antimicrobial nisin with trans-cinnamaldehyde and EDTA as a new approach for the inhibition of E. coli strains of swine origin.
      Citation: Antibiotics
      PubDate: 2017-12-12
      DOI: 10.3390/antibiotics6040035
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 36: Adverse Effects of Amoxicillin for Acute
           Lower Respiratory Tract Infection in Primary Care: Secondary and Subgroup
           Analysis of a Randomised Clinical Trial

    • Authors: Meera Tandan, Akke Vellinga, Robin Bruyndonckx, Paul Little, Theo Verheij, Chris Butler, Herman Goossens, Samuel Coenen
      First page: 36
      Abstract: A European placebo-controlled trial of antibiotic treatment for lower respiratory tract infection (LRTI) conducted in 16 primary care practices networks recruited participants between November 2007 and April 2010, and found adverse events (AEs) occurred more often in patients prescribed amoxicillin compared to placebo. This secondary analysis explores the causal relationship and estimates specific AEs (diarrhoea, nausea, rash) due to amoxicillin treatment for LRTI, and if any subgroup is at increased risk of any or a specific AE. A total of 2061 patients were randomly assigned to amoxicillin (1038) and placebo (1023); 595 (28%) were 60 and older. A significantly higher proportion of any AEs (diarrhoea or nausea or rash) (OR = 1.31, 95% CI 1.05–1.64, number needed to harm (NNH) = 24) and of diarrhoea (OR 1.43 95% CI 1.08–1.90, NNH = 29) was reported in the amoxicillin group during the first week after randomisation. Subgroup analysis showed rash was significantly more often reported in males prescribed amoxicillin (interaction term 3.72 95% CI 1.22–11.36; OR of amoxicillin in males 2.79 (95% CI 1.08–7.22). No other subgroup at higher risk was identified. Although the study was not powered for subgroup analysis, this analysis suggests that most patients are likely to be equally harmed when prescribed antibiotics.
      Citation: Antibiotics
      PubDate: 2017-12-13
      DOI: 10.3390/antibiotics6040036
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 37: LC-MS/MS Tandem Mass Spectrometry for
           Analysis of Phenolic Compounds and Pentacyclic Triterpenes in Antifungal
           Extracts of Terminalia brownii (Fresen)

    • Authors: Enass Salih, Pia Fyhrquist, Ashraf Abdalla, Abdelazim Abdelgadir, Markku Kanninen, Marketta Sipi, Olavi Luukkanen, Mustafa Fahmi, Mai Elamin, Hiba Ali
      First page: 37
      Abstract: Decoctions and macerations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as fungicides on field crops and in traditional granaries in Sudan. In addition, T. brownii water extracts are commonly used as sprays for protecting wooden houses and furniture. Therefore, using agar disc diffusion and macrodilution methods, eight extracts of various polarities from the stem wood and bark were screened for their growth-inhibitory effects against filamentous fungi commonly causing fruit, vegetable, grain and wood decay, as well as infections in the immunocompromised host. Ethyl acetate extracts of the stem wood and bark gave the best antifungal activities, with MIC values of 250 µg/mL against Nattrassia mangiferae and Fusarium verticillioides, and 500 µg/mL against Aspergillus niger and Aspergillus flavus. Aqueous extracts gave almost as potent effects as the ethyl acetate extracts against the Aspergillus and Fusarium strains, and were slightly more active than the ethyl acetate extracts against Nattrassia mangiferae. Thin layer chromatography, RP-HPLC-DAD and tandem mass spectrometry (LC-MS/MS), were employed to identify the chemical constituents in the ethyl acetate fractions of the stem bark and wood. The stem bark and wood were found to have a similar qualitative composition of polyphenols and triterpenoids, but differed quantitatively from each other. The stilbene derivatives, cis- (3) and trans- resveratrol-3-O-β-galloylglucoside (4), were identified for the first time in T. brownii. Moreover, methyl-(S)-flavogallonate (5), quercetin-7-β-O-di-glucoside (8), quercetin-7-O-galloyl-glucoside (10), naringenin-4′-methoxy-7-pyranoside (7), 5,6-dihydroxy-3′,4′,7-tri-methoxy flavone (12), gallagic acid dilactone (terminalin) (6), a corilagin derivative (9) and two oleanane type triterpenoids (1) and (2) were characterized. The flavonoids, a corilagin derivative and terminalin, have not been identified before in T. brownii. We reported earlier on the occurrence of methyl-S-flavogallonate and its isomer in the roots of T. brownii, but this is the first report on their occurrence in the stem wood as well. Our results justify the traditional uses of macerations and decoctions of T. brownii stem wood and bark for crop and wood protection and demonstrate that standardized extracts could have uses for the eco-friendly control of plant pathogenic fungi in African agroforestry systems. Likewise, our results justify the traditional uses of these preparations for the treatment of skin infections caused by filamentous fungi.
      Citation: Antibiotics
      PubDate: 2017-12-13
      DOI: 10.3390/antibiotics6040037
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 38: Decreasing Inappropriate Use of Antibiotics
           in Primary Care in Four Countries in South America—Cluster Randomized
           Controlled Trial

    • Authors: Inés Urbiztondo, Lars Bjerrum, Lidia Caballero, Miguel Suarez, Monica Olinisky, Gloria Córdoba
      First page: 38
      Abstract: High antibiotic prescribing and antimicrobial resistance in patients attending primary care have been reported in South America. Very few interventions targeting general practitioners (GPs) to decrease inappropriate antibiotic prescribing have been investigated in this region. This study assessed the effectiveness of online feedback on reducing antibiotic prescribing in patients with suspected respiratory tract infections (RTIs) attending primary care. The aim was to reduce antibiotic prescribing in patients with acute bronchitis and acute otitis media. Both are RTIs for which antibiotics have a very limited effect. A cluster randomized two-arm control trial was implemented. Healthcare centres from Bolivia, Argentina, Paraguay and Uruguay participating in the quality improvement program HAPPY AUDIT were randomly allocated to either intervention or control group. During ten consecutive weeks, GPs in the intervention group received evidence-based online feedback on the management of suspected RTIs. In patients with acute bronchitis, the intervention reduced the antibiotic prescribing rate from 71.6% to 56% (control group from 61.2% to 52%). In patients with acute otitis media, the intervention reduced the antibiotic prescribing from 94.8% to 86.2% (no change in the control group). In all RTIs, the intervention reduced antibiotic prescribing rate from 37.4% to 28.1% (control group from 29% to 27.2%). Online evidence-based feedback is effective for reducing antibiotic prescribing in patients with RTIs attending primary care in South America.
      Citation: Antibiotics
      PubDate: 2017-12-14
      DOI: 10.3390/antibiotics6040038
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 39: Six-Year Retrospective Review of Hospital
           Data on Antimicrobial Resistance Profile of Staphylococcus aureus Isolated
           from Skin Infections from a Single Institution in Greece

    • Authors: Christina Stefanaki, Alexandra Ieronymaki, Theoni Matoula, Chrysseis Caroni, Evaggelia Polythodoraki, Stella-Eugenia Chryssou, George Kontochristopoulos, Christina Antoniou
      First page: 39
      Abstract: Objective: To determine the prevalence of resistant strains of Staphylococcus aureus (S. aureus) isolated from Skin and soft tissue infections (SSTI) to various antibiotics. Material and Methods: All culture-positive results for S. aureus from swabs taken from patients presenting at one Greek hospital with a skin infection between the years 2010–2015 were examined retrospectively. Bacterial cultures, identification of S. aureus and antimicrobial susceptibility testing were performed using the disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines and European Committee on Antimicrobial testing (EUCAST) breakpoints. EUCAST breakpoints were applied if no CLSI were available. Results: Of 2069 S. aureus isolates identified, 1845 (88%) were resistant to one or more antibiotics. The highest resistance was observed for benzylpenicillin (71.9%), followed by erythromycin (34.3%). Resistant strains to cefoxitin defined as MRSA (methicillin-resistant S. aureus) represented 21% of total isolates. Interestingly, resistance to fusidic acid was 22.9% and to mupirocin as high as 12.7%. Low rates were observed for minocycline, rifampicin and trimethoprim/sulfamethoxazole (SXT). Resistance to antibiotics remained relatively stable throughout the six-year period, with the exception of cefoxitin, fusidic acid and SXT. A high percentage of MRSA strains were resistant to erythromycin (60%), fusidic acid (46%), clindamycin (38%) and tetracycline (35.5%). Conclusions: Special attention is required in prescribing appropriate antibiotic therapeutic regimens, particularly for MRSA. These data on the susceptibility of S. aureus may be useful for guiding antibiotic treatment.
      Citation: Antibiotics
      PubDate: 2017-12-20
      DOI: 10.3390/antibiotics6040039
      Issue No: Vol. 6, No. 4 (2017)
       
  • Antibiotics, Vol. 6, Pages 13: Antibacterial Activity and Toxicity of
           Analogs of Scorpion Venom IsCT Peptides

    • Authors: Roberto de la Salud Bea, Adam Petraglia, Michael Ascuitto, Quentin Buck
      First page: 13
      Abstract: Seven analogs of the natural, α-helix peptides IsCT1 and IsCT2—found in the venom of scorpion Opithancatus Madagascariensis—have been synthesized and tested to compare their antibacterial and hemolytic activity against natural peptides. In general, results show that increasing hydrophobicity by substituting positions 5 and 9 of the sequences with alanine, valine, and leucine, enhances antibacterial activity. However, this also increases hemolytic activity. The analog with an increased net positive charge from +1 to +3 produces moderate bacterial growth inhibition but also has high hemolytic activity. On the other hand, the analog with a negative net charge (−1) has low antibacterial properties but also no cytotoxicity under the tested conditions, a similar result was found for five of the seven studied analogs.
      PubDate: 2017-06-28
      DOI: 10.3390/antibiotics6030013
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 14: Macromolecular Conjugate and Biological
           Carrier Approaches for the Targeted Delivery of Antibiotics

    • Authors: Nhan Tram, Pui Ee
      First page: 14
      Abstract: For the past few decades, the rapid rise of antibiotic multidrug-resistance has presented a palpable threat to human health worldwide. Meanwhile, the number of novel antibiotics released to the market has been steadily declining. Therefore, it is imperative that we utilize innovative approaches for the development of antimicrobial therapies. This article will explore alternative strategies, namely drug conjugates and biological carriers for the targeted delivery of antibiotics, which are often eclipsed by their nanomedicine-based counterparts. A variety of macromolecules have been investigated as conjugate carriers, but only those most widely studied in the field of infectious diseases (e.g., proteins, peptides, antibodies) will be discussed in detail. For the latter group, blood cells, especially erythrocytes, have been successfully tested as homing carriers of antimicrobial agents. Bacteriophages have also been studied as a candidate for similar functions. Once these alternative strategies receive the amount of research interest and resources that would more accurately reflect their latent applicability, they will inevitably prove valuable in the perennial fight against antibiotic resistance.
      PubDate: 2017-07-04
      DOI: 10.3390/antibiotics6030014
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 15: Comparative Study on Antistaphylococcal
           Activity of Lipopeptides in Various Culture Media

    • Authors: Maciej Jaśkiewicz, Damian Neubauer, Wojciech Kamysz
      First page: 15
      Abstract: Staphylococcus aureus bacteria are one of the leading microorganisms responsible for nosocomial infections as well as being the primary causative pathogen of skin and wound infections. Currently, the therapy of staphylococcal diseases faces many difficulties, due to a variety of mechanisms of resistance and virulence factors. Moreover, a number of infections caused by S. aureus are connected with biofilm formation that impairs effectiveness of the therapy. Short cationic lipopeptides that are designed on the basis of the structure of antimicrobial peptides are likely to provide a promising alternative to conventional antibiotics. Many research groups have proved a high antistaphylococcal potential of lipopeptides, however, the use of different protocols for determination of antimicrobial activity may be the reason for inconsistency of the results. The aim of this study was to learn how the use of various bacteriological media as well as solvents may affect activity of lipopeptides and their cyclic analogs. Obtained results showed a great impact of these variables. For example, cyclic analogs were more effective when dissolved in an aqueous solution of acetic acid and bovine serum albumin (BSA). The greater activity against planktonic cultures was found in brain-heart infusion broth (BHI) and tryptic-soy broth (TSB), while the antibiofilm activity was higher in the Mueller-Hinton medium.
      Citation: Antibiotics
      PubDate: 2017-08-02
      DOI: 10.3390/antibiotics6030015
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 16: Self-Assessment of Antimicrobial
           Stewardship in Primary Care: Self-Reported Practice Using the TARGET
           Primary Care Self-Assessment Tool

    • Authors: Rebecca Owens, Leah Jones, Michael Moore, Dirk Pilat, Cliodna McNulty
      First page: 16
      Abstract: Multifaceted antimicrobial stewardship (AMS) interventions including: antibiotic guidance, reviews of antibiotic use using audits, education, patient facing materials, and self-assessment, are successful in improving antimicrobial use. We aimed to measure the self-reported AMS activity of staff completing a self-assessment tool (SAT). The Royal College of General Practitioners (RCGP)/Public Health England (PHE) SAT enables participants considering an AMS eLearning course to answer 12 short questions about their AMS activities. Questions cover guidance, audit, and reflection about antibiotic use, patient facing materials, and education. Responses are recorded digitally. Data were collated, anonymised, and exported into Microsoft Excel. Between November 2014 and June 2016, 1415 users completed the SAT. Ninety eight percent reported that they used antibiotic guidance for treating common infections and 63% knew this was available to all prescribers. Ninety four percent of GP respondents reported having used delayed prescribing when appropriate, 25% were not using Read codes, and 62% reported undertaking a practice-wide antibiotic audit in the last two years, of which, 77% developed an audit action plan. Twenty nine percent had undertaken other antibiotic-related clinical courses. Fifty six percent reported sharing patient leaflets covering infection. Many prescribers reported undertaking a range of AMS activities. GP practice managers should ensure that all clinicians have access to prescribing guidance. Antibiotic audits should be encouraged to enable GP staff to understand their prescribing behaviour and address gaps in good practice. Prescribers are not making full use of antibiotic prescribing-related training opportunities. Read coding facilitates more accurate auditing and its use by all clinicians should be encouraged.
      Citation: Antibiotics
      PubDate: 2017-08-16
      DOI: 10.3390/antibiotics6030016
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 17: Identification of Staphylococcus aureus
           Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a
           Microarray

    • Authors: William Schwan, Rebecca Polanowski, Paul Dunman, Sara Medina-Bielski, Michelle Lane, Marc Rott, Lauren Lipker, Amy Wescott, Aaron Monte, James Cook, Douglas Baumann, V.V.N. Tiruveedhula, Christopher Witzigmann, Cassandra Mikel, Md Rahman
      First page: 17
      Abstract: The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.
      Citation: Antibiotics
      PubDate: 2017-09-11
      DOI: 10.3390/antibiotics6030017
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 18: Synthesis and Immunological Evaluation of
           Virus-Like Particle-Milbemycin A3/A4 Conjugates

    • Authors: Andris Zeltins, Māris Turks, Dace Skrastina, Jevgeņija Lugiņina, Ieva Kalnciema, Ina Balke, Ērika Bizdēna, Vitalijs Skrivelis
      First page: 18
      Abstract: Milbemycins are macrolide antibiotics with a broad spectrum of nematocidal, insecticidal, and acaricidal activity. To obtain milbemycin A3/A4 derivatives suitable for chemical conjugation to protein carriers (milbemycin haptens), succinate linker and a novel 17-atom-long linker containing a terminal carboxylic acid group were attached to the milbemycin core in a protecting group-free synthesis. The obtained milbemycin A3/A4 derivatives were coupled to Potato virus Y-like nanoparticles by the activated ester method. The reaction products were characterized and used in mice immunization experiments. It was found that the mice developed weak specific immune responses toward all tested milbemycin haptens.
      Citation: Antibiotics
      PubDate: 2017-09-11
      DOI: 10.3390/antibiotics6030018
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 19: Point Prevalence Surveys of Antimicrobial
           Use among Hospitalized Children in Six Hospitals in India in 2016

    • Authors: Sumanth Gandra, Sanjeev Singh, Dasaratha Jinka, Ravishankar Kanithi, Ashok Chikkappa, Anita Sharma, Dhanya Dharmapalan, Anil Vasudevan, Onkaraiah Tunga, Akhila Akula, Garima Garg, Yingfen Hsia, Srinivas Murki, Gerardo Alvarez-Uria, Mike Sharland, Ramanan Laxminarayan
      First page: 19
      Abstract: The prevalence of antimicrobial resistance in India is among the highest in the world. Antimicrobial use in inpatient settings is an important driver of resistance, but is poorly characterized, particularly in hospitalized children. In this study, conducted as part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) project, we examined the prevalence of and indications of antimicrobial use, as well as antimicrobial agents used among hospitalized children by conducting four point prevalence surveys in six hospitals between February 2016 and February 2017. A total of 681 children were hospitalized in six hospitals across all survey days, and 419 (61.5%) were prescribed one or more antimicrobials (antibacterials, antivirals, antifungals). Antibacterial agents accounted for 90.8% (547/602) of the total antimicrobial prescriptions, of which third-generation cephalosporins (3GCs) accounted for 38.9% (213/547) and penicillin plus enzyme inhibitor combinations accounted for 14.4% (79/547). Lower respiratory tract infection (LRTI) was the most common indication for prescribing antimicrobials (149 prescriptions; 24.8%). Although national guidelines recommend the use of penicillin and combinations as first-line agents for LRTI, 3GCs were the most commonly prescribed antibacterial agents (55/149 LRTI prescriptions; 36.9%). In conclusion, 61.5% of hospitalized children were on at least one antimicrobial agent, with excessive use of 3GCs. Hence there is an opportunity to limit their inappropriate use.
      Citation: Antibiotics
      PubDate: 2017-09-13
      DOI: 10.3390/antibiotics6030019
      Issue No: Vol. 6, No. 3 (2017)
       
  • Antibiotics, Vol. 6, Pages 11: Erythromycin Modification That Improves Its
           Acidic Stability while Optimizing It for Local Drug Delivery

    • Authors: Erika Cyphert, Jaqueline Wallat, Jonathan Pokorski, Horst von Recum
      First page: 11
      Abstract: The antibiotic erythromycin has limited efficacy and bioavailability due to its instability and conversion under acidic conditions via an intramolecular dehydration reaction. To improve the stability of erythromycin, several analogs have been developed—such as azithromycin and clarithromycin—which decrease the rate of intramolecular dehydration. We set out to build upon this prior work by developing a conjugate of erythromycin with improved pH stability, bioavailability, and preferential release from a drug delivery system directly at the low pH of an infection site. To develop this new drug conjugate, adamantane-1-carbohydrazide was covalently attached to erythromycin via a pH-degradable hydrazone bond. Since Staphylococcus aureus infection sites are slightly acidic, the hydrazone bond will undergo hydrolysis liberating erythromycin directly at the infection site. The adamantane group provides interaction with the drug delivery system. This local delivery strategy has the potential of reducing off-target and systemic side-effects. This work demonstrates the synthesis of a pH-cleavable, erythromycin conjugate that retains the inherent antimicrobial activity of erythromycin, has an increased hydrophobicity, and improved stability in acidic conditions; thereby enhancing erythromycin’s bioavailability while simultaneously reducing its toxicity.
      PubDate: 2017-04-25
      DOI: 10.3390/antibiotics6020011
      Issue No: Vol. 6, No. 2 (2017)
       
  • Antibiotics, Vol. 6, Pages 12: Bacteria from Animals as a Pool of
           Antimicrobial Resistance Genes

    • Authors: Maria Argudín, Ariane Deplano, Alaeddine Meghraoui, Magali Dodémont, Amelie Heinrichs, Olivier Denis, Claire Nonhoff, Sandrine Roisin
      First page: 12
      Abstract: Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.
      PubDate: 2017-06-06
      DOI: 10.3390/antibiotics6020012
      Issue No: Vol. 6, No. 2 (2017)
       
  • Antibiotics, Vol. 6, Pages 1: Acknowledgement to Reviewers of Antibiotics
           in 2016

    • Authors: Antibiotics Office
      First page: 1
      Abstract: The editors of Antibiotics would like to express their sincere gratitude to the following reviewers  for assessing manuscripts in 2016.[...]
      PubDate: 2017-01-10
      DOI: 10.3390/antibiotics6010001
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 2: Fused-Ring Oxazolopyrrolopyridopyrimidine
           Systems with Gram-Negative Activity

    • Authors: Yiyuan Chen, Jonathan Moloney, Kirsten Christensen, Mark Moloney
      First page: 2
      Abstract: Fused polyheterocyclic derivatives are available by annulation of a tetramate scaffold, and been shown to have antibacterial activity against a Gram-negative, but not a Gram-positive, bacterial strain. While the activity is not potent, these systems are structurally novel showing, in particular, a high level of polarity, and offer potential for the optimization of antibacterial activity.
      PubDate: 2017-01-13
      DOI: 10.3390/antibiotics6010002
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 3: Thioridazine: A Non-Antibiotic Drug Highly
           Effective, in Combination with First Line Anti-Tuberculosis Drugs, against
           Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its
           Multi-Mechanisms of Action

    • Authors: Leonard Amaral, Miguel Viveiros
      First page: 3
      Abstract: This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.
      PubDate: 2017-01-14
      DOI: 10.3390/antibiotics6010003
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 4: Docking into Mycobacterium tuberculosis
           Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for
           Methicillin-Resistant Staphylococcus aureus

    • Authors: Noreena Sweeney, Lauren Lipker, Alicia Hanson, Chris Bohl, Katie Engel, Kelsey Kalous, Mary Stemper, Daniel Sem, William Schwan
      First page: 4
      Abstract: The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics.
      PubDate: 2017-01-28
      DOI: 10.3390/antibiotics6010004
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 5: Moxifloxacin Increases Heart Rate in Humans

    • Authors: Jay Mason, Thomas Moon
      First page: 5
      Abstract: (1) Background: We assessed the effect of moxifloxacin on heart rate, and reviewed the heart rate effects of other antibiotics; (2) Methods: A total of 335 normal volunteers had 12-lead electrocardiograms recorded at multiple time points before and during treatment with moxifloxacin and with placebo in seven consecutive, thorough QT studies of crossover design; (3) Results: The average baseline heart rate across the seven studies was 61.5 bpm. The heart rate after moxifloxacin dosing was analyzed at five time points shared by all seven studies (hours 1, 2, 3, 12 and 24). The maximum mean heart rate (HR) increase for the seven studies combined was 2.4 bpm (95% CI 1.6, 3.3) at hour 2. The range of mean maximum increases among the seven studies was 2.1 to 4.3 bpm. For the seven studies combined, the increase was statistically significant at all but the 24 h time point. The maximum observed individual increase in HR was 36 bpm and the mean maximum increase was 30 ± 4.1 bpm by time point and 8 ± 6.9 bpm by subject. Many antibiotics increase HR, some several-fold more than moxifloxacin. However, clinicians and clinical investigators give little attention to this potential adverse effect in the medical literature; (4) Conclusions: The observed moxifloxacin-induced increase in HR is large enough to be clinically relevant, and it is a potentially important confounder in thorough QT studies using moxifloxacin as an active control. More attention to heart rate effects of antibiotics is warranted.
      PubDate: 2017-02-05
      DOI: 10.3390/antibiotics6010005
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 6: Diminished Antimicrobial Peptide and
           Antifungal Antibiotic Activities against Candida albicans in Denture
           Adhesive

    • Authors: Amber Bates, Jorge Garaicoa, Carol Fischer, Kim Brogden
      First page: 6
      Abstract: The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti-Candida activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.0% denture adhesive were incubated with Candida albicans strains ATCC 64124 and HMV4C in radial diffusion assays. In gels with 1.0% adhesive, HNP-1, HBD2, HBD3, IP-10, LL37 (only one strain), histatin 5 (only one strain), lactoferricin B, and SMAP28 showed diminished activity against C. albicans. In gels with 1.0% adhesive, amphotericin B and chlorhexidine dihydrochloride were active against both strains of C. albicans. These results suggest that denture adhesive may inactivate innate immune mediators in the oral cavity increasing the risk of C. albicans infections, but inclusion of antifungal antibiotics to denture adhesive may aid in prevention or treatment of Candida infections and denture stomatitis.
      PubDate: 2017-02-06
      DOI: 10.3390/antibiotics6010006
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 7: Final Demonstration of the Co-Identity of
           Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray
           Analysis

    • Authors: Stefano Serra, Luciana Malpezzi, Angelo Bedeschi, Claudio Fuganti, Piera Fonte
      First page: 7
      Abstract: Lipiarmycin A3 and tiacumicin B possess the same chemical structure and have been considered identical till recently, when some authors have suggested the possibility of a minor difference between the chemical structures of the two antibiotics. In this work we performed a comparative X-ray analysis of lipiarmycin A3 and tiacumicin B. Although the commercial samples of the aforementioned compounds crystallize into two different crystal systems—evidently due to the different crystallization conditions—their chemical structures are identical. These results confirmed the previous assigned chemical structure of lipiarmycin A3 and its absolute configuration as well as its co-identity with the chemical structure of tiacumicin B, providing the definitive proof that these pharmaceutical compounds are identical in all respects.
      PubDate: 2017-02-08
      DOI: 10.3390/antibiotics6010007
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 8:
           Bulgecin A: The Key to a Broad‐Spectrum Inhibitor 
           That Targets Lytic Transglycosylases

    • Authors: Allison Williams, Richard Wheeler, Constance Thiriau, Ahmed Haouz, Muhamed‐Kheir Taha, Ivo Boneca
      First page: 8
      Abstract: Lytic transglycosylases (Lts) are involved in recycling, cell division, and metabolism of the peptidoglycan. They have been understudied for their usefulness as potential antibacterial targets due to their high redundancy in Gram‐negative bacteria. Bulgecin A is an O‐sulphonated glycopeptide that targets primarily soluble lytic tranglycosylases (Slt). It has been shown that bulgecin A increases the efficacy of β‐lactams that target penicillin bindings proteins (PBPs). Here, we present the high‐resolution crystal structure of LtgA from Neisseria meningitidis strain MC58, a membrane bound homolog of Escherichia coli Slt, in complex with bulgecin A. The LtgA‐bulgecin A complex reveals the mechanism of inhibition by bulgecin A at near atomic resolution. We further demonstrate that bulgecin A is not only a potent inhibitor of LtgA, but most importantly, it restores the efficacy of β‐lactam antibiotics in strains of N. meningitidis and Neisseria gonorrhoeae that have reduced susceptibility to β‐lactams. This is particularly relevant for N. gonorrhoeae where no vaccines are available. This work illustrates how best to target dangerous pathogens using a multiple drug target approach, a new and alternative approach to fighting antibiotic resistance.
      PubDate: 2017-02-22
      DOI: 10.3390/antibiotics6010008
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 9: A Risk Assessment of Antibiotic
           Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation
           Study

    • Authors: Daniel Carter, André Charlett, Stefano Conti, Julie Robotham, Alan Johnson, David Livermore, Tom Fowler, Mike Sharland, Susan Hopkins, Neil Woodford, Philip Burgess, Stephen Dobra
      First page: 9
      Abstract: To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07–0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400–58,600) and 22,800 (95% CrI: 1500–160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0–23,000) and 6400 (95% CrI: 0–64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000–1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0–821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance.
      PubDate: 2017-03-07
      DOI: 10.3390/antibiotics6010009
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 10: Activity of Sulfa Drugs and Their
           Combinations against Stationary Phase B. burgdorferi In Vitro

    • Authors: Jie Feng, Shuo Zhang, Wanliang Shi, Ying Zhang
      First page: 10
      Abstract: Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug–containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
      PubDate: 2017-03-22
      DOI: 10.3390/antibiotics6010010
      Issue No: Vol. 6, No. 1 (2017)
       
 
 
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