Activity loss by H46 mutation in Mycobacterium tuberculosis isocitrate lyase is due to decrease in structural plasticity and collective motions of the active site
Mycobacterium tuberculosis isocitrate lyase (MtbICL) is a crucial enzyme of the glyoxylate cycle and is a validated anti-tuberculosis drug target. Structurally distant, non-active site mutation (H46A) in MtbICL has been found to cause loss of enzyme activity. The aim of the present work was to explore the structural alterations induced by H46A mutation that caused the loss of enzyme activity. The structural and dynamic consequences of H46A mutation were studied using multiple computational methods such as docking, molecular dynamics simulation and residue interaction network analysis (RIN). (Source: Tuberculosis)
Source: Tuberculosis - November 29, 2017 Category: Respiratory Medicine Authors: Rohit Shukla, Harish Shukla, Timir Tripathi Source Type: research
A multicentre verification study of the QuantiFERON ®-TB Gold Plus assay
The aim of this verification study was to compare the QuantiFERON ®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent late nt tuberculosis infections. (Source: Tuberculosis)
Source: Tuberculosis - November 28, 2017 Category: Respiratory Medicine Authors: E.D. Pieterman, F. Liqui Lung, A. Verbon, H.I. Bax, C.W. Ang, J. Berkhout, G. Blaauw, A. Brandenburg, N.D. van Burgel, A. Claessen, K. van Dijk, M. Heron, M. Hooghiemstra, R. Leussenkamp-Hummelink, E. van Lochem, I.H.M. van Loo, B. Mulder, A. Ott, O. Pont Source Type: research
Rapid and sensitive method for simultaneous determination of first-line anti-tuberculosis drugs in human plasma by HPLC-MS/MS: Application to therapeutic drug monitoring
First-line anti-tuberculosis drugs are playing vital roles for curbing rapid spread of tuberculosis. Multidrug therapies are commonly applied in clinical to achieve better treatment outcomes. However, drug resistance and adverse reactions come along with this therapies and therapeutic drug monitoring is a feasible way to precaution them. For this reasons, a simple and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and single protein precipitation was developed and validated for simultaneously quantifying of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin in human plasma...
Source: Tuberculosis - November 24, 2017 Category: Respiratory Medicine Authors: Shouhong Gao, Zhipeng Wang, Xinfang Xie, Chunhua You, Yang Yang, Yanhai Xi, Wansheng Chen Source Type: research
Rapid and sensitive method for simultaneous determination of first-line anti-tuberculosis drugs in human plasma by HPLC-MS/MS: Application to therapeutic drug monitoring
First-line anti-tuberculosis drugs are playing vital roles for curbing rapid spread of tuberculosis. Multidrug therapies are commonly applied in clinical to achieve better treatment outcomes. However, drug resistance and adverse reactions come along with this therapies and therapeutic drug monitoring is a feasible way to precaution them. For this reasons, a simple and sensitive method based on liquid chromatography-tandem mass spectroscopy (LC-MS/MS) and single protein precipitation was developed and validated for simultaneously quantifying of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin in human plasma...
Source: Tuberculosis - November 24, 2017 Category: Respiratory Medicine Authors: Shouhong Gao, Zhipeng Wang, Xinfang Xie, Chunhua You, Yang Yang, Yanhai Xi, Wansheng Chen Source Type: research
Modulation of iron status biomarkers in tuberculosis-diabetes co-morbidity
Tuberculosis (TB) and diabetes mellitus (DM) remain vital disease burdens in developing countries and the dual burden of DM and TB clearly signifies a growing global public health concern. While modulation of iron status biomarkers in TB is well described, very little is known about the association of these markers with TB-DM. To examine the association of circulating iron status biomarkers in TB disease, we examined the systemic levels of ferritin, hepcidin, soluble transferrin receptor (sTfR), transferrin, apotransferrin and hemopexin in pulmonary TB (PTB) individuals with DM (PTB-DM), without DM (PTB) and those with dia...
Source: Tuberculosis - November 24, 2017 Category: Respiratory Medicine Authors: Nathella Pavan Kumar, Vaithilingam V. Banurekha, Dina Nair, Chandrakumar Dolla, Paul Kumaran, Subash Babu Source Type: research
Killer (FASL regulatory) B cells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis
Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. (Source: Tuberculosis)
Source: Tuberculosis - November 24, 2017 Category: Respiratory Medicine Authors: Ilana C. van Rensburg, A.G. Loxton Source Type: research
Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention
Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. (Source: Tuberculosis)
Source: Tuberculosis - November 22, 2017 Category: Respiratory Medicine Authors: Andrew Fiore-Gartland, Lindsay N. Carpp, Kogieleum Naidoo, Ethan Thompson, Daniel E. Zak, Steve Self, Gavin Churchyard, Gerhard Walzl, Adam Penn-Nicholson, Thomas J. Scriba, Mark Hatherill Source Type: research
Modeling the structural origins of drug resistance to isoniazid via key mutations in Mycobacterium tuberculosis catalase-peroxidase, KatG
WHO reported 10.4 million new tuberculosis (TB) cases and 1.8 million deaths in 2015, making M. tuberculosis the most successful human pathogen with highest mortality among infectious diseases [1],[2]. Drug-resistant TB is a major threat to global TB control [2,3]. Recently Torres et al. [4] identified 14 novel substitutions in M. tuberculosis-KatG (the enzyme associated with resistance to isoniazid —an important first-line anti-TB drug) and demonstrated that 12 of the 14 can cause INH-resistance in M. (Source: Tuberculosis)
Source: Tuberculosis - November 22, 2017 Category: Respiratory Medicine Authors: Matthew W. Marney, Robert P. Metzger, David Hecht, Faramarz Valafar Tags: Molecular Aspects Source Type: research
Considerations for biomarker-targeted intervention strategies for TB prevention
Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. (Source: Tuberculosis)
Source: Tuberculosis - November 22, 2017 Category: Respiratory Medicine Authors: Andrew Fiore-Gartland, Lindsay N. Carpp, Kogieleum Naidoo, Ethan Thompson, Daniel E. Zak, Steve Self, Gavin Churchyard, Gerhard Walzl, Adam Penn-Nicholson, Thomas J. Scriba, Mark Hatherill Source Type: research
Mycobacterium tuberculosis infection induces IL-10 gene expression by disturbing histone deacetylase 6 and histonedeacetylase 11 equilibrium in macrophages
Mycobacterium tuberculosis (MTB) infection is a significant contributor to dysregulated T cell-mediated immune response. Here we aimed to evaluate the mechanism of MTB infection in promoting interleukin-10 (IL-10) upregulation. The IL-10 levels in MTB infected THP-1 cells were evaluated with enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). In challenged THP-1 cells, the HDAC6 and HDAC11 mRNA and protein levels were monitored at varied duration after MTB infection. (Source: Tuberculosis)
Source: Tuberculosis - November 20, 2017 Category: Respiratory Medicine Authors: Xiaolei Wang, Yanhua Wu, Jin Jiao, Qing Huang Source Type: research
Quercetin 3-O-glucoside recovered from the wild Egyptian Sahara plant, Euphorbia paralias L., inhibits glutamine synthetase and has antimycobacterial activity
Tuberculosis remains a major health problem accentuated by the rise of resistance to all available drugs. Therefore, this study was launched to discover a novel antituberculosis agent from wild Egyptian Sahara plants. Twelve such plants were screened, in vitro, for their activity against various Mycobacterium species. The most active plant, Euphorbia paralias, was further fractionated with different organic solvents, and the activity of the obtained fractions was determined by the agar diffusion and broth microdilution methods. (Source: Tuberculosis)
Source: Tuberculosis - November 15, 2017 Category: Respiratory Medicine Authors: Nesreen A. Safwat, Mona T. Kashef, Ramy K. Aziz, Khadiga F. Amer, Mohammed A. Ramadan Tags: Drug Discovery and Resistance Source Type: research
Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines
The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Gur éin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaqu es were infected with BCG by intradermal injection. (Source: Tuberculosis)
Source: Tuberculosis - November 15, 2017 Category: Respiratory Medicine Authors: Stephanie A. Harris, Andrew White, Lisa Stockdale, Rachel Tanner, Laura Sibley, Charlotte Sarfas, Joel Meyer, Jonathan Peter, Matthew K. O'Shea, Zita-Rose Manjaly Thomas, Ali Hamidi, Iman Satti, Mike J. Dennis, Helen McShane, Sally Sharpe Tags: Model Systems Source Type: research
Should all suspected tuberculosis cases in high income countries be tested with GeneXpert?
The increasing threat of multidrug-resistanttuberculosis (MDR-TB) poses a seriouschallenge to the control of TB [1]. Rifampicin resistance is a good marker of MDR-TB [2], defined as combined resistance to both rifampicin and isoniazid. GeneXpert ® MTB/RIF [3,4] is a rapid molecular assay for the diagnosis of TB and rifampicin resistance in patient specimens and it can be used close to the point of care with minimal technical expertise [5]. (Source: Tuberculosis)
Source: Tuberculosis - November 8, 2017 Category: Respiratory Medicine Authors: Venanzio Vella, Agnieszka Broda, Francis Drobniewski Source Type: research
