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RESPIRATORY DISEASES (103 journals)                     

Showing 1 - 103 of 103 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 249)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 19)
American Review of Respiratory Disease     Full-text available via subscription   (Followers: 4)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Annals of the American Thoracic Society     Full-text available via subscription   (Followers: 16)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
Archivos de Bronconeumología     Full-text available via subscription  
Archivos de Bronconeumología (English Edition)     Full-text available via subscription   (Followers: 1)
Asthma Research and Practice     Open Access   (Followers: 1)
BMC Pulmonary Medicine     Open Access   (Followers: 4)
BMJ Open Respiratory Research     Open Access   (Followers: 5)
Breathe     Open Access   (Followers: 4)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal  
Canadian Respiratory Journal     Open Access   (Followers: 2)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 102)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 3)
Clinical Pulmonary Medicine     Hybrid Journal   (Followers: 2)
COPD Research and Practice     Open Access   (Followers: 1)
COPD: Journal of Chronic Obstructive Pulmonary Disease     Hybrid Journal   (Followers: 15)
Current Opinion in Pulmonary Medicine     Hybrid Journal   (Followers: 10)
Current Pulmonology Reports     Hybrid Journal  
Current Research in Tuberculosis     Open Access   (Followers: 3)
Current Respiratory Care Reports     Hybrid Journal   (Followers: 1)
Current Respiratory Medicine Reviews     Hybrid Journal   (Followers: 5)
Der Pneumologe     Hybrid Journal   (Followers: 1)
Egyptian Journal of Chest Diseases and Tuberculosis     Open Access   (Followers: 3)
ERJ Open Research     Open Access   (Followers: 2)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 3)
European Respiratory Journal     Full-text available via subscription   (Followers: 38)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal  
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 11)
Heart, Lung and Circulation     Full-text available via subscription   (Followers: 9)
Indian Journal of Respiratory Care     Open Access   (Followers: 3)
Indian Journal of Tuberculosis     Full-text available via subscription  
Influenza and Other Respiratory Viruses     Open Access   (Followers: 2)
International Journal of Chronic Obstructive Pulmonary Disease     Open Access   (Followers: 3)
Journal of Association of Chest Physicians     Open Access   (Followers: 2)
Journal of Asthma     Hybrid Journal   (Followers: 4)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 3)
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases     Open Access  
Journal of Heart and Lung Transplantation     Hybrid Journal   (Followers: 12)
Journal of Respiratory Medicine     Open Access   (Followers: 4)
Journal of Respiratory Research     Open Access   (Followers: 1)
Journal of Tuberculosis Research     Open Access   (Followers: 1)
Jurnal Respirasi     Open Access  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Kindheit und Entwicklung     Hybrid Journal  
Lung     Hybrid Journal   (Followers: 2)
Lung Cancer     Hybrid Journal   (Followers: 15)
Lung Cancer International     Open Access   (Followers: 2)
Lung Cancer: Targets and Therapy     Open Access   (Followers: 3)
Lung India     Open Access   (Followers: 1)
Multidisciplinary Respiratory Medicine     Open Access   (Followers: 4)
npj Primary Care Respiratory Medicine     Open Access   (Followers: 2)
Open Journal of Respiratory Diseases     Open Access   (Followers: 1)
Open Respiratory Medicine Journal     Open Access   (Followers: 1)
Paediatric Respiratory Reviews     Hybrid Journal   (Followers: 12)
Pediatric Quality & Safety     Open Access  
Pediatric Respirology and Critical Care Medicine     Open Access   (Followers: 1)
Pulmonary Circulation     Open Access   (Followers: 4)
Pulmonary Medicine     Open Access   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 1)
Pulmonology and Respiratory Research     Open Access   (Followers: 1)
Respiratory Care     Full-text available via subscription   (Followers: 10)
Respiratory Investigation     Full-text available via subscription  
Respiratory Medicine     Hybrid Journal   (Followers: 17)
Respiratory Medicine : X     Open Access  
Respiratory Medicine Case Reports     Open Access  
Respiratory Medicine CME     Hybrid Journal  
Respiratory Medicine Extra     Full-text available via subscription   (Followers: 1)
Respiratory Medicine: COPD Update     Hybrid Journal   (Followers: 5)
Respiratory Physiology & Neurobiology     Hybrid Journal   (Followers: 4)
Respiratory Research     Open Access   (Followers: 1)
Respirology     Hybrid Journal   (Followers: 5)
Respirology Case Reports     Open Access  
Revista Americana de Medicina Respiratoria     Open Access  
Revista Chilena de Enfermedades Respiratorias     Open Access  
Revista Inspirar     Open Access  
Revista ORL     Open Access  
Revista Portuguesa de Pneumologia     Open Access  
Sarcoidosis Vasculitis and Diffuse Lung Disese     Full-text available via subscription   (Followers: 3)
Seminars in Respiratory and Critical Care Medicine     Hybrid Journal   (Followers: 14)
Sleep Medicine Reviews     Hybrid Journal   (Followers: 17)
The Clinical Respiratory Journal     Hybrid Journal   (Followers: 3)
The International Journal of Tuberculosis and Lung Disease     Full-text available via subscription   (Followers: 8)
The Lancet Respiratory Medicine     Full-text available via subscription   (Followers: 32)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 37)
Translational Respiratory Medicine     Open Access   (Followers: 1)
Tuberculosis     Hybrid Journal   (Followers: 12)
Tuberculosis Research and Treatment     Open Access   (Followers: 3)
Пульмонология     Full-text available via subscription  

           

Similar Journals
Journal Cover
Tuberculosis
Journal Prestige (SJR): 1.264
Citation Impact (citeScore): 3
Number of Followers: 12  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1472-9792
Published by Elsevier Homepage  [3177 journals]
  • Mycobacterium tuberculosis strains of the modern Beijing sublineage
           excessively accumulate triacylglycerols in vitro
    • Abstract: Publication date: Available online 22 November 2019Source: TuberculosisAuthor(s): Jingfeng Tong, Qingyun Liu, Jie Wu, Yuan Jiang, Howard E. Takiff, Qian GaoAbstractMycobacterium tuberculosis (Mtb) strains of modern Beijing sublineage appear to be more transmissible and cause more severe disease than strains of other sublineages, but the responsible pathogenic mechanisms remain unclear. We previously identified genetic changes that are specific for the modern Beijing sublineage, and here we characterize the lipidome and transcriptome differences between modern and ancient Beijing sublineages. We report that modern Beijing strains accumulated 2.89 (95%CI: 2.05–3.73) times more triacylglycerol (TAG) than ancient Beijing strains in vitro. We also observed that modern Beijing strains had a 2.64-fold (95%CI: 1.29–4.00) upregulation of tgs2 (annotated as TAG synthetase 2), whose role in TAG accumulation was further confirmed in Mycobacterium marinum (Mm). Because TAG serves as a crucial carbon source and reservoir of free fatty acids, the results suggest that the excessive accumulation of TAG might fuel the growth of modern Beijing strains after infection and lead to rapid development of disease.
       
  • N6-methylated adenine on the target sites of mamA from Mycobacterium bovis
           BCG enhances macrophage activation by CpG DNA in mice
    • Abstract: Publication date: Available online 18 November 2019Source: TuberculosisAuthor(s): Yumiko Tsukamoto, Toshiki Tamura, Maeda Yumi, Kensuke Miyake, Manabu AtoCpG motifs in DNA sequences are recognized by Toll-like receptor 9 and activate immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases (5-methylcytosine [5 mC]) and modified adenine bases (6-methyladenine [6 mA]). 5 mC inhibits immune activation by CpG DNA; however, it is unclear whether 6 mA inhibits immune activation by CpG DNA. Mycobacterium bovis BCG (BCG) has three adenine methyltransferases (MTases) that act on specific target sequences. In this study, we examined whether the 6  mA at the target sites of adenine MTases affected the immunostimulatory activity of CpG DNA. Our results showed that only 6 mA located at the target sequence of mamA, an adenine MTase from BCG, enhanced interleukin (IL)-12p40 production from murine bone marrow-derived macrophages (BMDMs) stimulated with CpG DNA. Enhancement of IL-12p40 production in BMDMs was also observed when BMDMs were stimulated with CpG DNA ligated to oligodeoxynucleotides (ODNs) harboring 6 mA. Accordingly, we then evaluated whether gDNA from adenine MTase-deficient BCG was less efficient with regard to stimulation of BMDMs. Indeed, gDNA from a mamA-deficient BCG had less ability to activate BMDMs than that from wild-type BCG. We concluded from these results that adenine methylation on ODNs and bacterial gDNA may enhance immune activity induced by CpG DNA.Graphical abstractImage 1
       
  • WQ-3810: A new fluoroquinolone with a high potential against
           fluoroquinolone-resistant Mycobacterium tuberculosis
    • Abstract: Publication date: Available online 18 November 2019Source: TuberculosisAuthor(s): Yuki Ouchi, Tetsu Mukai, Kentaro Koide, Tomoyuki Yamaguchi, Jong-Hoon Park, Hyun Kim, Kazumasa Yokoyama, Aki Tamaru, Stephen V. Gordon, Chie Nakajima, Yasuhiko SuzukiAbstractFluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro antimycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette–Guérin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains.
       
  • Characterization of a novel Mycobacterium tuberculosis serine protease
           (Rv3194c) activity and pathogenicity
    • Abstract: Publication date: Available online 4 November 2019Source: TuberculosisAuthor(s): He Li, Guanghui Dang, Hongxiu Liu, Zhongxing Wang, Ziyin Cui, Ningning Song, Liping Chen, Siguo LiuAbstractMycobacterium tuberculosis (MTB) serine proteases are important pathogen-associated virulence factors that are involved in the invasion, bacterial persistence, and degradation of host defense factors. The current study identified and characterized a novel serine protease, Rv3194c, of MTB. A heterologous Rv3194c protein, purified from Escherichia coli, possessed proteolytic activity that could hydrolyze bovine serum albumin (BSA), milk, casein, and gelatin at an optimal temperature of 40 °C and a pH of 8.0. Furthermore, the divalent metal ions Ca2+ and Mn2+ increased the activity of Rv3194c. Betulinic acid, a Traditional Chinese Medicine (TCM) monomer; PMSF, a chemical inhibitor; and the Roche inhibitor cocktail inhibited proteolytic activity. Site-directed mutagenesis demonstrated that D308 and particularly S309 play a crucial role in the catalytic activity of Rv3194c protease. The cellular assays revealed that Rv3194c inhibits THP1-derived macrophage migration. Moreover, Rv3194c degraded the complement components, C3b and C5a, causing inhibition of phagocytosis and chemotaxis. In mice, Rv3194c enhanced the persistence of Mycobacterium smegmatis (Ms) in the lung, induced lung lesions, and promoted the release of inflammatory cytokines. The results of this study indicate that Rv3194c may play an important role in the pathogenicity of mycobacteria.
       
  • Catabolism of 8-oxo-purines is mainly routed via the guanine to xanthine
           interconversion pathway in Mycobacterium smegmatis
    • Abstract: Publication date: Available online 31 October 2019Source: TuberculosisAuthor(s): Zdeněk Knejzlík, Klára Herkommerová, Iva PichováAbstractMetabolism of purine bases remains poorly understood in the pathogenic bacterium Mycobacterium tuberculosis and closely related, nonpathogenic Mycobacterium smegmatis (Msm). To gain insight into the purine metabolism in mycobacteria, we tested uptake of purine bases with a ΔpurF Msm mutant with an inactive purine de novo biosynthesis pathway and confirmed that hypoxanthine and guanine, but not xanthine, can serve as nucleotide precursors for recycling in the salvage pathway. Further, we focused on purine catabolism in wild-type (wt) Msm. We found that only xanthine and guanine could serve as a sole nitrogen source for wt Msm. These data confirm that Msm catabolism of purines is directed mainly via oxidative guanine to xanthine interconversion and not through metabolic conversion of hypoxanthine to xanthine. Our data represent the first experimental evidence confirming the use of 8-oxo-purines as a nitrogen source by Msm.
       
  • Diagnostic accuracy of molecular detection of Mycobacterium tuberculosis
           in pediatric stool samples: A systematic review and meta-analysis
    • Abstract: Publication date: Available online 23 October 2019Source: TuberculosisAuthor(s): Annelies W. Mesman, Carly Rodriguez, Emily Ager, Julia Coit, Letizia Trevisi, Molly F. FrankeBackgroundStool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or ‘in-house’ molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity.MethodsWe searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children.Results–We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96–99], pooled sensitivity was 57% [95%CI: 40–72] against culture and 3% [95%CI: 2–6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%).Conclusion–Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting.
       
  • Publisher's note
    • Abstract: Publication date: September 2019Source: Tuberculosis, Volume 118Author(s):
       
  • High expression of BTLA and B7-H4 on the surface of myeloid dendritic
           cells has a negative regulatory effect on their anti-tuberculosis immunity
           activity in pleural tuberculosis patients
    • Abstract: Publication date: Available online 11 October 2019Source: TuberculosisAuthor(s): Xiaozhen Cai, Nanhai Ge, Rong Rong, Yuanbin Lu, Junai Zhang, Junfa XuAbstractTo investigate the effects of the surface markers B- and T-lymphocyte attenuator (BTLA) and B7 homologous body 4 (B7-H4) on expression of CD83, and Human Leukocyte Antigen–DR isotype (HLA-DR) that can activate dendritic cells (DCs). Flow cytometry was used to detect the co-expression of BTLA and B7-H4 on myeloid DCs (mDCs) in peripheral blood (PB) and pleural effusions (PE) in 15 volunteers and 20 tuberculous pleurisy (TP) patients. Co-expression of BTLA and B7-H4 (double positive (DP)) mDCs in PB and PE of TP patients were enhanced. The proportion of DP mDC in PB decreased markedly after 2 weeks treatment, but was still greater than in controls. Expression of CD83 and HLA-DR on DP mDCs was higher than on BTLA and B7-H4 double negative (DN) expressing mDCs in PB of different TP groups. Expression of CD83 on DP mDCs in TP peripheral blood and PE was greater than that in control PB. Expression of HLA-DR on DP mDCs in TP patient PB was lower than in TP PE and controls. In pleural tuberculosis (TB) patients, high expression of BTLA and B7-H4 promoted a high level of CD83 and HLA-DR, which had a negative regulatory effect on mDCs on anti-TB immunity.
       
  • Impact of individual-level factors on Ex vivo mycobacterial growth
           inhibition: Associations of immune cell phenotype,
           cytomegalovirus-specific response and sex with immunity following BCG
           vaccination in humans
    • Abstract: Publication date: Available online 30 September 2019Source: TuberculosisAuthor(s): Satria A. Prabowo, Steven G. Smith, Karin Seifert, Helen A. FletcherAbstractUnderstanding factors associated with varying efficacy of Bacillus Calmette-Guérin (BCG) would aid the development of improved vaccines against tuberculosis (TB). In addition, investigation of individual-level factors affecting mycobacterial-specific immune responses could provide insight into confounders of vaccine efficacy in clinical trials. Mycobacterial growth inhibition assays (MGIA) have been developed to assess vaccine immunogenicity ex vivo and provide a measure of immune function against live mycobacteria. In this study, we assessed the impact of immune cell phenotype, cytomegalovirus (CMV)-specific response and sex on ex vivo growth inhibition following historical BCG vaccination in a cohort of healthy individuals (n = 100). A higher frequency of cytokine-producing NK cells in peripheral blood was associated with enhanced ex vivo mycobacterial growth inhibition following historical BCG vaccination. A CMV-specific response was associated with T-cell activation, a risk factor for TB disease and we also observed an association between T-cell activation and ex vivo mycobacterial growth. Interestingly, BCG-vaccinated females in our cohort controlled mycobacterial growth better than males. In summary, our present study has shown that individual-level factors influence capacity to control mycobacterial growth following BCG vaccination and the MGIA could be used as a tool to assess how vaccine candidates may perform in different populations.
       
  • Resolving a clinical tuberculosis outbreak using palaeogenomic genome
           reconstruction methodologies
    • Abstract: Publication date: Available online 23 September 2019Source: TuberculosisAuthor(s): Rhys Jones, Marcela Sandoval Velasco, Llinos G. Harris, Sue Morgan, Mark Temple, Michael Ruddy, Rhian Williams, Michael Perry, Matt Hitchings, Thomas S. Wilkinson, Thomas Humphrey, M. Thomas P. Gilbert, Angharad Puw DaviesAbstractThis study describes the analysis of DNA from heat-killed (boilate) isolates of Mycobacterium tuberculosis from two UK outbreaks where DNA was of sub-optimal quality for the standard methodologies routinely used in microbial genomics. An Illumina library construction method developed for sequencing ancient DNA was successfully used to obtain whole genome sequences, allowing analysis of the outbreak by gene-by-gene MLST, SNP mapping and phylogenetic analysis. All cases were spoligotyped to the same Haarlem H1 sub-lineage. This is the first described application of ancient DNA library construction protocols to allow whole genome sequencing of a clinical tuberculosis outbreak. Using this method it is possible to obtain epidemiologically meaningful data even when DNA is of insufficient quality for standard methods.
       
  • Comparison of the Mycobacterium tuberculosis molecular bacterial load
           assay, microscopy, and GeneXpert versus liquid culture for viable
           bacterial load quantification before and after starting pulmonary
           tuberculosis treatment
    • Abstract: Publication date: Available online 21 September 2019Source: TuberculosisAuthor(s): Hai Hoang T, Dao N. Vinh, Do DA. Thu, Nguyen T. Hanh, Nguyen Hoan Phu, Srinivasan Vijay, Guy E. Thwaites, Nguyen TT ThuongAbstractMolecular bacterial load assay (MBLA) rapidly quantifies viable Mycobacterium tuberculosis (Mtb) and may be useful for monitoring treatment response and treatment efficacy.We conducted a prospective study in 56 adults with pulmonary tuberculosis from whom 244 sputum samples were collected before and during the first month of treatment. We evaluated MBLA for early monitoring of bacterial burden and investigated bactericidal activities of first-line therapy in patients infected with drug susceptible and resistant isolates.Mtb loads measured by MBLA and culture were correlated after one-week (r = 0.56) and one-month (r = 0.73) of treatment. Correlations between culture and GeneXpert or microscopy were weaker during treatment. Mtb load by MBLA declined more rapidly than GeneXpert after one-week (2.73 Ct, P 
       
  • TB-IRIS pathogenesis and new strategies for intervention: Insights from
           related inflammatory disorders
    • Abstract: Publication date: Available online 13 September 2019Source: TuberculosisAuthor(s): Paula M. Cevaal, Linda-Gail Bekker, Sabine HermansAbstractIn almost one in five HIV/tuberculosis (TB) co-infected patients, initiation of antiretroviral therapy (ART) is complicated by TB immune reconstitution inflammatory syndrome (TB-IRIS). Corticosteroids have been suggested for treatment of severe cases, however no therapy is currently licensed for TB-IRIS. Hence, there is a strong need for more specific therapeutics, and therefore, a better understanding of TB-IRIS pathogenesis. Immune reconstitution following ART is a precariously balanced functional restoration of adaptive immunity. In those patients predisposed to disease, an incomplete activation of the innate immune system leads to a hyper-inflammatory response that comprises partially overlapping innate, adaptive and effector arms, eventually leading to clinical symptoms. Interestingly, many of these pathological mechanisms are shared by related inflammatory disorders. We here describe therapeutic strategies that originate from these other disciplines and discuss their potential application in TB-IRIS. These new avenues of interventions range from final-phase treatment of symptoms to early-phase prevention of disease onset. In conclusion, we propose a novel approach for the discovery and development of therapeutics, based on an updated model of TB-IRIS pathogenesis. Further experimental studies validating the causal relationships in the proposed model could greatly contribute to providing a solid immunological basis for future clinical trials on TB-IRIS therapeutics.
       
  • Kinetic analysis of DNA compaction by mycobacterial integration host
           factor at the single-molecule level
    • Abstract: Publication date: Available online 9 September 2019Source: TuberculosisAuthor(s): Yuanyuan Chen, Zhengyan Zhan, Hongtai Zhang, Lijun Bi, Xian-En Zhang, Yu Vincent FuAbstractNucleoid-associated proteins (NAPs) play an important role on chromosome condensation and organization. Mycobacterial integration host factor (mIHF) is one of the few mycobacterial NAPs identified so far. mIHF has the ability to stimulate mycobacteriophage L5 integration and compact DNA into nucleoid-like or higher order filamentous structures by atomic force microscopy observation. In this study, M. smegmatis IHF (MsIHF), which possesses the sequence essential for mIHF's functions, binds 30-bp dsDNA fragments in a sequence-independent manner and displays sensitivity to ion strength in bio-layer interferometry (BLI) experiments. The DNA compaction process of MsIHF was observed at the single-molecule level using the total internal reflection fluorescence microscopy (TIRFM). MsIHF efficiently compacted λ DNA into a highly condensed structure with the concentration of 0.25 and 1.0 μM, and the packing ratios were higher than 10. Further kinetic analysis revealed MsIHF compacts DNA in a three-step mechanism, which consists of two compaction steps with different compacting rates separated by a lag step. This study would help us better understand the mechanisms of chromosomal DNA organization in mycobacteria.
       
  • Histone deacetylase inhibitors impair the host immune response against
           Mycobacterium tuberculosis infection
    • Abstract: Publication date: Available online 27 August 2019Source: TuberculosisAuthor(s): Chuanzhi Zhu, Yi Cai, Jialou Zhu, Lanyue Zhang, Aiying Xing, Liping Pan, Hongyan Jia, Siwei Mo, Carl G. Feng, Hongbo Shen, Xinchun Chen, Zongde ZhangAbstractHistone deacetylase inhibitors (HDACi), a novel class of anti-cancer drug, have been recently reported to suppress host immunity and increase susceptibility to infection. Tuberculosis, a leading infectious disease killer caused by Mycobacterium tuberculosis (M.tb), is basically the product of the interaction between bacterial virulence and host resistance. However, the effects of HDACi in host immunity against M.tb is largely unknown. In this study, we found that HDACi including Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) significantly impaired phagocytosis and killing activity of macrophage. In line with these findings, we noted that M.tb induced reactive oxygen species (ROS) production and autophagy are significantly suppressed by TSA. Transcriptome analysis revealed that the suppression of autophagy by TSA might due to its inhibiting autophagy-regulating genes such as CACNA2D3, which regulates intracellular Ca2+ levels. Finally, we confirmed that HDACi including TSA and SAHA significantly exacerbated the histopathological damage and M.tb load in the lung of M.tb infected mice. Taken together, our results indicated that HDACi at least TSA and SAHA significantly impaired macrophage immunity against M.tb and therefore increase susceptibility to TB, our findings raised the concern that the potential side effects of HDACi on latent TB reactivation should be considered in clinic.
       
  • Developing new TB biomarkers, are miRNA the answer'
    • Abstract: Publication date: Available online 21 August 2019Source: TuberculosisAuthor(s): Jessica L. Pedersen, Nilesh J. Bokil, Bernadette M. SaundersAbstractEfforts to reduce the global TB burden are hindered by the lack of simple, reliable non-sputum based diagnostics. To date studies investigating the biomarker potential of circulating host proteins and mRNA have not shown sufficient diagnostic utility. Recently, there has been increasing interest in circulating miRNA as a biomarker of TB disease. This review examined all published miRNA-TB biomarker studies to determine if a reproducible miRNA signature of TB disease could be elucidated. From 15 miRNA profiling studies, 894 miRNA differentially expressed between TB patients and healthy controls were identified in at least one study. Of these, 143 miRNA were validated by qPCR with 53 differentially expressed between TB patients and controls. Interestingly, only 8 of these miRNA were identified in 2 or more studies, and no consensus on a reproducible miRNA signature for identification of TB disease could be identified. TB disease is clearly associated with a wide breadth of differentially expressed miRNA. This review highlights our recent progress and the multiple factors, including environment, source of tissue, ethnicity and extent of TB disease that may influence miRNA expression. Coordinated efforts are required to validate identified targets in multiple populations to progress miRNA biomarker development.
       
  • Distinct serum biosignatures are associated with different tuberculosis
           treatment outcomes
    • Abstract: Publication date: Available online 12 August 2019Source: TuberculosisAuthor(s): Katharina Ronacher, Novel N. Chegou, Léanie Kleynhans, Joel F. Djoba-Siawaya, Nelita du Plessis, André G. Loxton, Elizna Maasdorp, Gerard Tromp, Martin Kidd, Kim Stanley, Magdalena Kriel, Angela Menezes, Andrea Gutschmidt, Gian D. van der Spuy, Robin M. Warren, Reynaldo Dietze, Alphonse Okwera, Bonnie Thiel, John T. Belisle, Jacqueline M. CliffAbstractBiomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-β, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38–1) and 85% specificity (95%CI 0.75–0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58–1) sensitivity and 61% (95%CI 0.39–0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.
       
  • Diminished type 1 and type 17 cytokine expressing - Natural killer cell
           frequencies in tuberculous lymphadenitis
    • Abstract: Publication date: September 2019Source: Tuberculosis, Volume 118Author(s): Gokul Raj Kathamuthu, Nathella Pavan Kumar, Kadar Moideen, Rathinam Sridhar, Dhanaraj Baskaran, Subash BabuAbstractTuberculous lymphadenitis (TBL) is associated with the expansion of CD4+ and CD8+ T cells expressing Type 1 and Type 17 cytokines in the peripheral blood. However, the expression pattern of cytokine producing natural killer (NK) cells in both the peripheral blood and affected lymph nodes i.e. site of infection in TBL have not been examined. Hence, we have analyzed the baseline and mycobacterial antigen specific NK cell cytokine frequencies in whole blood of TBL and pulmonary tuberculosis (PTB) individuals. We have also examined the NK cell frequencies before and after treatment completion and in peripheral blood versus affected lymph nodes (LN) of TBL individuals. TBL is characterized by diminished frequencies of NK cells expressing Type 1 (IFNγ, TNFα), Type 17 (IL-17F) cytokines compared to PTB individuals upon antigen-specific stimulation. In contrast, TBL individuals did not exhibit any significant differences in the frequencies of NK cells expressing Type 1 and Type 17 cytokines upon completion of anti-tuberculosis treatment. LN of TBL is associated with altered frequencies of NK cells expressing Type 17 (increased IL-17F and decreased IL-22) cytokines when compared to peripheral blood. Thus, we conclude that TBL individuals are characterized by diminished frequencies of NK cells expressing Type 1/Type 17 cytokines.
       
  • Molecular epidemiology of M. tuberculosis in Ethiopia: A systematic review
           and meta-analysis
    • Abstract: Publication date: Available online 7 August 2019Source: TuberculosisAuthor(s): Daniel Mekonnen, Awoke Derbie, Asmamaw Chanie, Abebe Shumet, Fantahun Biadglegne, Yonas Kassahun, Kidist Bobosha, Adane Mihret, Liya Wassie, Abaineh Munshae, Endalkachew Nibret, Solomon Abebe Yimer, Tone Tønjum, Abraham AseffaAbstractNationally representative molecular epidemiology information about Mycobacterium tuberculosis (M. tuberculosis, Mtb) is lacking for Ethiopia. This review summarizes available literature on the genomic diversity, geo-spatial distribution and transmission patterns of M. tuberculosis lineages (L) and sublineages in Ethiopia. Spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) based articles were identified from MEDLINE via PubMed and Scopus. The last date of article search was 12th February 2019. Articles were selected following the PRISMA flow diagram. The proportion of (sub)lineages was summarized at national level and further disaggregated by region. Clustering and recent transmission index (RTI) were determined using Matan command and random effect meta-analysis model. The meta-analysis was computed using Stata 14 (Stata Corp. College Station, TX, USA). Among a total of 4371 clinical isolates, 99.5% were Mtb and 0.5% were M. bovis. Proportionally, L4, L3, L1 and L7 made up 62.3%, 21.7%, 7.9% and 3.3% of the total respectively. Among sublineages, L4.2. ETH/SIT149, L4.10/SIT53, L3. ETH1/SIT25 and L4.6/SIT37 were the leading clustered isolates accounting for 14.4%, 9.7%, 7.2% and 5.5%, respectively. Based on MIRU-VNTR, the rate of clustering was 41% and the secondary case rate from a single source case was estimated at 29%. Clustering and recent transmission index was higher in eastern and southwestern Ethiopia compared with northwest Ethiopia. High level of genetic diversity with a high rate of clustering was noted which collectively mirrored the phenomena of micro-epidemics and super-spreading. The largest set of clustered strains deserves special attention and further characterization using whole genome sequencing (WGS) to better understand the evolution, genomic diversity and transmission dynamics of Mtb.
       
  • “It's time!” ...to make a change: Cat Stevens' commitment to the
           elimination of tuberculosis
    • Abstract: Publication date: Available online 6 August 2019Source: TuberculosisAuthor(s): Ilaria Barberis, Mariano Martini
       
  • Mycobacterium bovis sigF mutant exhibits altered surface phenotype and
           compromised pathogenesis
    • Abstract: Publication date: Available online 31 July 2019Source: TuberculosisAuthor(s): Debashis Dutta, Vishal Srivastava, Ashutosh Tripathi, Vandana Singh, Mohd Mustkim Ansari, Garima Pant, Manisha Mishra, Sharad Sharma, Jagadehswar Reddy Thota, Pradhyumna Kumar Singh, Bhupendra N. Singh
       
  • Effects of membrane lipid composition on Mycobacterium tuberculosis EsxA
           membrane insertion: A dual play of fluidity and charge
    • Abstract: Publication date: Available online 30 July 2019Source: TuberculosisAuthor(s): Supriyo Ray, Salvador Reyes, Chuan Xiao, Jianjun SunAbstractAs a key virulence factor of Mycobacterium tuberculosis, EsxA or 6-kDa early secreted antigenic target (ESAT-6) has been implicated in phagosome rupture and mycobacterial translocation from the phagosome to the cytosol within macrophages. Our previous studies have shown that EsxA permeabilizes liposomal membrane at acidic pH and a membrane-permeabilization defective mutant Q5K attenuates mycobacterial cytosolic translocation and virulence in macrophages. To further probe the mechanism of EsxA membrane permeabilization, here we characterized the effects of various lipid compositions, including biologically relevant phagosome-mimicking lipids and lipid rafts, on the structural stability and membrane insertion of EsxA WT and Q5K. We have found a complex dual play of membrane fluidity and charge in regulating EsxA membrane insertion. Moreover, Q5K affects the membrane insertion through a structure- and lipid composition-independent mechanism. The results of this study provide a novel insights into the mechanism of EsxA membrane interaction.
       
  • In silico and in vitro evaluation of tetrahydropyridine compounds as
           efflux inhibitors in Mycobacterium abscessus
    • Abstract: Publication date: Available online 23 July 2019Source: TuberculosisAuthor(s): Ivy B. Ramis, Júlia S. Vianna, Lande Silva Junior, Andrea von Groll, Daniela F. Ramos, Nilo Zanatta, Miguel Viveiros, Pedro E. Almeida da SilvaAbstractHerein, we evaluated tetrahydropyridine (THP) compounds (NUNM) as antimicrobials and inhibitors of the efflux mechanism in M. abscessus. subsp. abscessus. The modulation factor (MF) of efflux inhibitors was calculated from the minimum inhibitory concentrations (MICs) of amikacin (AMI), ciprofloxacin (CIP) and clarithromycin (CLA) in the absence and presence of subinhibitory concentrations of the NUNM compounds and canonical inhibitors carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and verapamil (VP). The kinetics of the intracellular accumulation of the fluorimetric substrate ethidium bromide (EtBr) was evaluated and calculated by the relative final fluorescence (RFF). In addition, molecular modeling simulations for the MmpL5 and Tap efflux transporters with ligands (CLA, NUNM, CCCP, VP and EtBr) were performed to better understand the efflux mechanism. We highlight the NUNM01 compound because it reduced the MICs of AMI, CIP and CLA by 4-, 4- and 16-fold, respectively, had the highest effect on EtBr accumulation (RFF = 3.1) and showed a significant in silico affinity for the evaluated proteins in docking simulations. Based on the analyses performed in vitro and in silico, we propose that NUNM01 is a potential pharmacophore candidate for the development of a therapeutic adjuvant for M. abscessus infections.
       
  • DARPin based GMR biosensor for the detection of ESAT-6 tuberculosis
           protein
    • Abstract: Publication date: Available online 20 July 2019Source: TuberculosisAuthor(s): Shagun Gupta, Vipan KakkarAbstractTuberculosis (TB), a life threatening communicable disease, is mainly caused by the bacterium named Mycobacterium tuberculosis (MTB). This high burden infectious threat is the ninth leading killer disease worldwide and also the foremost cause of death from a single infectious agent, even ranking above HIV/AIDS. In this work, a novel magnetic biosensing technique based on giant magneto-resistance (GMR) has been proposed for the on-field detection of Tuberculosis (TB) through assessment of MTB specific protein- ESAT-6. This portable highly sensitive diagnostic tool provides the results with a low turnaround time and the achieved limit of detection in the range of pg/ml can be a breakthrough in TB diagnostics. In addition, the use of DARPins (designed ankyrin repeat proteins) leads to high specificity and help in early detection, thus enabling early onset of treatment and thereby reduced mortality. This study compares the results of conventional and GNP-ELISA and it has been shown that the proposed GMR technique is more sensitive. Further, the effect of different sized magnetic nanoparticles on the performance of GMR biosensor is also presented.
       
  • A standardized BioBrick toolbox for the assembly of sequences in
           mycobacteria
    • Abstract: Publication date: Available online 19 July 2019Source: TuberculosisAuthor(s): Thaís Larré Oliveira, Anna Stedman, Caroline Rizzi, Jessica Dorneles, Carlos Eduardo Pouey da Cunha, Antonio Sergio Varela Junior, Odir Antônio Dellagostin, Johnjoe McFaddenAbstractFor more than 25 years, recombinant Mycobacterium bovis BCG has been genetically engineered for use as a vehicle for antigen expression and immunomodulation, typically through introducing or deleting a gene from BCG genome. However, BCG transformation efficacy is still unpredictable, and cloning and expression of sequences from mycobacteria is difficult to predict due to the lack of standardization. To overcome such limitations, we have employed the BioBrick format to construct a toolbox of several mycobacterial parts, including coding sequences, reporter genes, selective markers, promoters, and other regulatory sequences. Additionally, we have developed and characterized BioBrick-compatible episomal vectors that are able to replicate in M. bovis BCG to enable expression of heterologous antigens. The availability of a BCG Biobrick toolbox will enable any coding sequence to be optimally expressed in BCG. We believe that this mycobacterial toolbox represents a standardized and useful kit to enhance the efficacy and use of recombinant BCG.
       
 
 
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