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Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access  
3D Printing in Medicine     Open Access   (Followers: 2)
4 open     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 5)
ABCS Health Sciences     Open Access   (Followers: 7)
Abia State University Medical Students' Association Journal     Full-text available via subscription   (Followers: 2)
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 45)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
Acta Bioethica     Open Access  
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Científica Estudiantil     Open Access  
Acta Facultatis Medicae Naissensis     Open Access  
Acta Herediana     Open Access  
Acta Informatica Medica     Open Access   (Followers: 1)
Acta Medica (Hradec Králové)     Open Access  
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
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Acta Medica Indonesiana     Open Access  
Acta Medica International     Open Access  
Acta medica Lituanica     Open Access  
Acta Medica Marisiensis     Open Access  
Acta Medica Martiniana     Open Access  
Acta Medica Nagasakiensia     Open Access   (Followers: 1)
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Acta Médica Portuguesa     Open Access  
Acta Medica Saliniana     Open Access  
Acta Scientiarum. Health Sciences     Open Access   (Followers: 1)
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 6)
Acupuncture and Natural Medicine     Open Access  
Addiction Science & Clinical Practice     Open Access   (Followers: 8)
Addictive Behaviors Reports     Open Access   (Followers: 9)
Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / Health Sciences Journal of Adıyaman University     Open Access  
Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi     Open Access  
Advanced Biomedical Research     Open Access  
Advanced Health Care Technologies     Open Access   (Followers: 6)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 8)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 6)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26)
Advances in Life Course Research     Hybrid Journal   (Followers: 9)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Medical Education and Practice     Open Access   (Followers: 31)
Advances in Medical Ethics     Open Access   (Followers: 1)
Advances in Medical Research     Open Access   (Followers: 1)
Advances in Medical Sciences     Hybrid Journal   (Followers: 8)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Medicine     Open Access   (Followers: 3)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4)
Advances in Molecular Oncology     Open Access   (Followers: 3)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7)
Advances in Parkinson's Disease     Open Access  
Advances in Phytomedicine     Full-text available via subscription  
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Regenerative Medicine     Open Access   (Followers: 3)
Advances in Skeletal Muscle Function Assessment     Open Access  
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 5)
Advances in Wound Care     Hybrid Journal   (Followers: 12)
Aerospace Medicine and Human Performance     Full-text available via subscription   (Followers: 12)
African Health Sciences     Open Access   (Followers: 3)
African Journal of Biomedical Research     Open Access   (Followers: 1)
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 2)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 3)
African Journal of Trauma     Open Access   (Followers: 1)
Afrimedic Journal     Open Access   (Followers: 2)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AJOB Primary Research     Partially Free   (Followers: 3)
AJSP: Reviews & Reports     Hybrid Journal  
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 4)
Al-Azhar Assiut Medical Journal     Open Access   (Followers: 2)
ALERTA : Revista Científica del Instituto Nacional de Salud     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 4)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 2)
Althea Medical Journal     Open Access   (Followers: 2)
American Journal of Biomedical Engineering     Open Access   (Followers: 13)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 7)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 4)
American Journal of Clinical Medicine Research     Open Access   (Followers: 7)
American Journal of Family Therapy     Hybrid Journal   (Followers: 11)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 11)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 5)
American Journal of Managed Care     Full-text available via subscription   (Followers: 11)
American Journal of Medical Case Reports     Open Access   (Followers: 1)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 4)
American Journal of Medicine     Hybrid Journal   (Followers: 51)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Studies     Open Access   (Followers: 2)
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 10)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 5)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 5)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 6)
Anatolian Clinic the Journal of Medical Sciences     Open Access  
Anatomica Medical Journal     Open Access  
Anatomical Science International     Hybrid Journal   (Followers: 3)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy     Open Access   (Followers: 2)
Anatomy Research International     Open Access   (Followers: 3)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Ankara Medical Journal     Open Access   (Followers: 2)
Ankara Üniversitesi Tıp Fakültesi Mecmuası     Open Access  
Annales de Pathologie     Full-text available via subscription  
Annales des Sciences de la Santé     Open Access  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 2)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 3)
Annals of Bioanthropology     Open Access   (Followers: 4)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 17)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 3)
Annals of Clinical Hypertension     Open Access  
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 12)
Annals of Family Medicine     Open Access   (Followers: 14)
Annals of Health Research     Open Access  
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 7)
Annals of Microbiology     Hybrid Journal   (Followers: 11)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Rehabilitation Medicine     Open Access  
Annals of Saudi Medicine     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 5)
Annual Review of Medicine     Full-text available via subscription   (Followers: 17)
Anthropological Review     Open Access   (Followers: 23)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Technology Journal     Open Access   (Followers: 1)
Antibody Therapeutics     Open Access  
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 3)
Applied Clinical Research, Clinical Trials and Regulatory Affairs     Hybrid Journal   (Followers: 1)
Applied Medical Informatics     Open Access   (Followers: 12)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access   (Followers: 1)
Archives Medical Review Journal / Arşiv Kaynak Tarama Dergisi     Open Access  
Archives of Asthma, Allergy and Immunology     Open Access  
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 3)
Archives of Medicine and Surgery     Open Access  
Archives of Trauma Research     Open Access   (Followers: 3)
Archivos de Medicina (Manizales)     Open Access  
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access   (Followers: 1)
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access  
Ars Medica : Revista de Ciencias Médicas     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Full-text available via subscription   (Followers: 16)
Arterial Hypertension     Open Access   (Followers: 1)
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 16)
Artificial Organs     Hybrid Journal   (Followers: 1)
ASHA Leader     Open Access  
Asia Pacific Family Medicine     Open Access   (Followers: 1)
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 11)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Biomedicine     Open Access   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 4)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 2)
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Transfusion Science     Open Access   (Followers: 1)
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Cancer Prevention     Open Access  
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 1)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Audiology - Communication Research     Open Access   (Followers: 10)
Auris Nasus Larynx     Full-text available via subscription  
Australian Coeliac     Full-text available via subscription   (Followers: 1)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 1)
Autopsy and Case Reports     Open Access  

        1 2 3 4 5 6 7 8 | Last

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Journal Prestige (SJR): 1.063
Citation Impact (citeScore): 3
Number of Followers: 9  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2079-6382
Published by MDPI Homepage  [215 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

    • 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

    • 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

    • 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

    • 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’

    • 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)
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