Centrifugation and decontamination procedures selectively impair recovery of important populations in Mycobacterium smegmatis
Diagnosis and treatment monitoring of patients with tuberculosis (TB) requires detection of all viable mycobacteria in clinical samples. Quantitation of Mycobacterium tuberculosis (Mtb) in sputum is commonly performed by culture after sample decontamination to prevent overgrowth by contaminant organisms. Exponentially growing cultures have cells that predominately lack non-polar lipid bodies whereas stationary cultures have a predominance of cells with non-polar lipid bodies. This may reflect rapidly growing ‘active’ and non-replicating ‘persister’ sub-populations respectively in sputum from TB patients. (Source: Tuberculosis)
Source: Tuberculosis - August 1, 2018 Category: Respiratory Medicine Authors: John A. Kennedy, Vincent O. Baron, Robert J.H. Hammond, Derek J. Sloan, Stephen H. Gillespie Source Type: research
Human tuberculosis brain promotes neuronal apoptosis but not in astrocytes with high expression of vascular endothelial growth factor
The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). (Source: Tuberculosis)
Source: Tuberculosis - July 18, 2018 Category: Respiratory Medicine Authors: Fatihah N. Othman, Sangu Muthuraju, Siti Suraiya M. Noor, Sarimah Abdullah, Abdul A.M. Yusoff, John Tharakan, Shalini Bhaskar, Mohd S. Mahmood, Fauziah Kassim, Md H. Rafia, Mohammed S.M. Haspani, Azmi Alias, Rogelio H. Pando, Jafri M. Abdullah, Hasnan Jaa Tags: Mechanisms of Pathogenesis Source Type: research
IMB-SD62, a triazolothiadiazoles derivative with promising action against tuberculosis
One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified as an inhibitor of shikimate dehydrogenase with antitubercular activity. Following up this compound, we optimized the lead through systematic modification of the 3 and 6 positions. The antitubercular activities in vitro, shikimate dehydrogenase inhibitory activities and cytotoxicity of derivatives were determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus, we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis and pharmacokinetics of IMB-SD62. (Source: Tuberculosis)
Source: Tuberculosis - July 17, 2018 Category: Respiratory Medicine Authors: Qi Deng, Jianzhou Meng, Yishuang Liu, Yan Guan, Chunling Xiao Source Type: research
Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis
The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment. (Source: Tuberculosis)
Source: Tuberculosis - July 17, 2018 Category: Respiratory Medicine Authors: Komal Kedia, Jason Wendler, Erin S. Baker, Kristin E. Burnum-Johnson, Leah G. Jarsberg, Kelly G. Stratton, Aaron T. Wright, Paul D. Piehowski, Marina A. Gritsenko, David M. Lewinsohn, George B. Sigal, Marc H. Weiner, Richard D. Smith, Jon M. Jacobs, Payam Tags: Immunological Aspects Source Type: research
In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge
In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN- γ-secreting CD8+ T cells in splenocytes. (Source: Tuberculosis)
Source: Tuberculosis - July 9, 2018 Category: Respiratory Medicine Authors: Jiansong Tang, Yi Cai, Jianguo Liang, Zhiwu Tan, Xian Tang, Chi Zhang, Lin Cheng, Jingying Zhou, Haibo Wang, Wing-Cheong Yam, Xinchun Chen, Hui Wang, Zhiwei Chen Source Type: research
Generation and application of DNA aptamers against HspX for accurate diagnosis of tuberculous meningitis
Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis and its diagnosis remains a challenge even today due to the lack of an adequate test. HspX antigen of Mycobacterium tuberculosis was previously established as a reliable diagnostic biomarker for TBM in an ELISA test format using anti-HspX polyclonal antibodies. Towards overcoming the limitations of batch-to-batch variation and challenges of scalability in antibody generation, we utilized Systematic Evolution of Ligands by EXponential enrichment (SELEX) to develop high affinity DNA aptamers against HspX as an alternative diagnostic reagent. (Source: Tuberculosis)
Source: Tuberculosis - July 9, 2018 Category: Respiratory Medicine Authors: Abhijeet Dhiman, Sagarika Haldar, Subodh Kumar Mishra, Neera Sharma, Anjali Bansal, Yusra Ahmad, Amit Kumar, Tarun Kumar Sharma, Jaya Sivaswami Tyagi Tags: Diagnostics Source Type: research
A genotypic and spatial epidemiologic analysis of Massachusetts' Mycobacterium tuberculosis cases from 2012 to 2015
Massachusetts had a rate of 2.8 cases of tuberculosis (TB) per 100,000 individuals in 2015. Although TB in Massachusetts is on the decline, the case rate remains far above the 2020 National TB Target of 1.4 per 100,000. To reduce the TB case rate in Massachusetts, it is necessary to understand the local epidemiology and transmission risks. (Source: Tuberculosis)
Source: Tuberculosis - July 4, 2018 Category: Respiratory Medicine Authors: T. Vindenes, M.R. Jordan, A. Tibbs, T.J. Stopka, D. Johnson, J. Cochran Source Type: research
Mycobacterium tuberculosis cording in alveolar macrophages of patients with pulmonary tuberculosis is likely associated with increased mycobacterial virulence
Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis (TB) in humans. A study of the volume of Mtb population and the detection of Mtb virulence in the lungs of patients with pulmonary TB are of great importance for understanding the infectious process and the outcome of the disease. We analyzed the functional state of Mtb and their number in alveolar macrophages obtained from the resected lungs of patients with TB in ex vivo culture and determined that the number of Mtb, referred mainly to the Beijing genotype family (A0 and B0/W148 clusters), were significantly different in cells between differ...
Source: Tuberculosis - July 3, 2018 Category: Respiratory Medicine Authors: Elena G. Ufimtseva, Natalya I. Eremeeva, Ekaterina M. Petrunina, Tatiana V. Umpeleva, Sergey I. Bayborodin, Diana V. Vakhrusheva, Sergey N. Skornyakov Tags: Diagnostics Source Type: research
Anti-Mycobacterium tuberculosis activity of naphthoimidazoles combined with isoniazid and rifampicin
Tuberculosis (TB) is the cause of more than one million deaths worldwide, and despite being a curable disease, some factors can make therapy difficult, emphasizing the need for the development of new drugs that may potentiate the action of the classic anti-TB antimicrobials. Naphthoimidazoles show a broad spectrum of biological activities, including antimycobacterial activity. The aim of this study was to evaluate the anti-Mycobacterium tuberculosis activity of nine naphthoimidazoles, alone and combined with isoniazid (INH) and rifampicin (RIF). (Source: Tuberculosis)
Source: Tuberculosis - July 2, 2018 Category: Respiratory Medicine Authors: L élia Pacheco Corrêa Barros, Karina Pena Del Rio, Tatiane dos Santos Conceição Carvalho, Maria do Carmo Freire Ribeiro Pinto, Kelly Cristina Gallan de Moura, Priscila Cristina Bartolomeu Halicki, Daniela Fernandes Ramos, Pedro Eduardo Almeida da Silv Tags: Drug Discovery and Resistance Source Type: research
An unbiased attitude is vital to exploring the Beijing genotype of Mycobacterium tuberculosis
In 2003 Werngren and Hoffner reported the earliest quantitative mutability study comparing Beijing and non-Beijing strains of Mycobacterium tuberculosis. Their null findings appeared to be at odds with the then-popular hypothesis favoring characterization of the Beijing genotype by mutability. Three recent attempts to reexamine the experimental data have resulted in three successively smaller p-values in the literature, each supposedly buttressing a non-null conclusion. In addition to identifying errors responsible for the three misleading p-values, we focus on salutary lessons that will facilitate future research on micro...
Source: Tuberculosis - July 2, 2018 Category: Respiratory Medicine Authors: Qi Zheng, Jim Werngren Tags: Drug Discovery and Resistance Source Type: research
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(Source: Tuberculosis)
Source: Tuberculosis - July 1, 2018 Category: Respiratory Medicine Source Type: research
Alternate pathway to ascorbate induced inhibition of Mycobacterium tuberculosis
In this study, we observed that ascorbate can inhibit M. tuberculosis isocitrate lyase (MtbICL) with an IC50 of 2.15 mΜ. MtbICL is an essential enzyme for the survival of M. tuberculosis under dormancy. We studied the effect of ascorbate on the growth of M. (Source: Tuberculosis)
Source: Tuberculosis - June 20, 2018 Category: Respiratory Medicine Authors: Harish Shukla, Shaheb Raj Khan, Rohit Shukla, Manju Yasoda Krishnan, Md. Sohail Akhtar, Timir Tripathi Tags: Drug Discovery and Resistance Source Type: research
Deletion of PPAR γ in lung macrophages provides an immunoprotective response against M. tuberculosis infection in mice
Peroxisome proliferator-activated receptor gamma (PPAR γ) is a nuclear transcription factor belonging to the superfamily of ligand-activated nuclear receptors. It is activated by diverse endogenous lipid metabolites as well as by exogenous ligands such as the thiazolidinediones. Its activity regulates cellular metabolism, proliferation, differentiation , and inflammation, the latter in part through trans-repression of pro-inflammatory cytokines. PPARγ is highly expressed in alternatively activated alveolar macrophages (AMs), a primary host cell for airborne Mycobacterium tuberculosis (M. (Source: Tuberculosis)
Source: Tuberculosis - June 20, 2018 Category: Respiratory Medicine Authors: Evelyn Guirado, Murugesan VS. Rajaram, Ajay Chawla, Joanna Daigle, Krista MD. La Perle, Eusondia Arnett, Joanne Turner, Larry S. Schlesinger Tags: Immunological Aspects Source Type: research
Metabolomics of colistin methanesulfonate treated Mycobacterium tuberculosis
Over the last 5 years, there has been a renewed interest in finding new compounds with anti-TB action. Colistin methanesulfonate or polymyxin E, is a possible anti-TB drug candidate, which may in future be used either alone or in combination to the current 6 month “directly observed treatment short-course” (DOTS) regimen. However its mechanism of action has to date not yet been fully explored, and only described from a histological and genomics perspective. Considering this, we used a GCxGC-TOFMS metabolomics approach and identified those metabolite marke rs characterising Mycobacterium tuberculosis (Mtb) cultured in t...
Source: Tuberculosis - June 13, 2018 Category: Respiratory Medicine Authors: Nadia Koen, Shane Vontelin van Breda, Du Toit Loots Source Type: research
Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection
The QuantiFERON-TB Gold Plus (QFT-Plus) is a new test for latent tuberculosis infection (LTBI) diagnosis, in which has been added a new tube containing shorter peptides stimulating CD8 T-cells and CD4-stimulating-peptides. Measurement of alternative biomarkers to Interferon- γ (IFN-γ) in QFT-Plus may improve its sensitivity. Interferon-γ inducible protein 10 (IP-10), has been proposed as a tuberculosis (TB) biomarker. We aimed to evaluate the IP-10 accuracy in QFT-Plus for LTBI diagnosis.QFT-Plus was performed in 36 active TB, 31 LTBI and 16 healthy donors (HD). (Source: Tuberculosis)
Source: Tuberculosis - June 12, 2018 Category: Respiratory Medicine Authors: Linda Petrone, Valentina Vanini, Teresa Chiacchio, Elisa Petruccioli, Gilda Cuzzi, Vincenzo Schinin à, Fabrizio Palmieri, Giuseppe Ippolito, Delia Goletti Source Type: research
