Down-regulation of malate synthase in Mycobacterium tuberculosis H37Ra leads to reduced stress tolerance, persistence and survival in macrophages
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin. (Source: Tuberculosis)
Source: Tuberculosis - July 17, 2017 Category: Respiratory Medicine Authors: Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh Source Type: research
The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission
In endemic countries more than 20% of tuberculosis (TB) cases are in infants and children. Current animal models study TB during adulthood but animal models for infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and infant TB including natural transmission. In these studies, two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with hyper-virulent clinical strain W-Beijing Mycobacterium tuberculosis (Mtb) HN878 and were monitored for 11 or 36 weeks post-challeng...
Source: Tuberculosis - July 14, 2017 Category: Respiratory Medicine Authors: Laylaa Ramos, Andres Obregon-Henao, Marcela Henao-Tamayo, Richard Bowen, Joan K. Lunney, Mercedes Gonzalez-Juarrero Source Type: research
Real-time PCR followed by high-resolution melting curve analysis: A rapid and pragmatic approach for screening of multidrug-resistant extrapulmonary tuberculosis
Multidrug resistance (MDR) in extrapulmonary tuberculosis (EPTB) is a diagnostic challenge in an endemic country like India. Timely detection of MDR-TB can contribute to a better patient outcome. (Source: Tuberculosis)
Source: Tuberculosis - July 5, 2017 Category: Respiratory Medicine Authors: Kusum Sharma, Megha Sharma, Shreya Singh, Manish Modi, Aman Sharma, Pallab Ray, Subhash Varma Tags: Diagnostics Source Type: research
Immunological characterization of latent tuberculosis infection in a low endemic country
The diagnosis of a latent tuberculosis infection (LTBI) is based on detection of immunity against Mycobacterium tuberculosis (Mtb). The tuberculin skin test (TST), the Quantiferon (QFT) and a prolonged lymphocyte stimulation test using either ESAT-6/CFP-10 (LST-EC) or PPD (LST-PPD) were evaluated in a cohort of 495 individuals, suspected to have LTBI, in a low endemic country. While the TST and LST-PPD were both positive in the majority (75%) of individuals, only one third responded in the LST-EC and in the QFT. (Source: Tuberculosis)
Source: Tuberculosis - July 4, 2017 Category: Respiratory Medicine Authors: Roelof A. de Paus, Krista E. van Meijgaarden, Corine Prins, Margreet H. Kamphorst, Sandra M. Arend, Tom H.M. Ottenhoff, Simone A. Joosten Tags: Immunological Aspects Source Type: research
Detection of Mycobacterium tuberculosis from paraffin-embedded tissues by GeneXpert MTB/RIF
In this study we provide a Xpert-dedicated successful protocol for processing paraffin-embedded tissue and assess the feasibility of the Xpert assay-based tuberculosis (TB) diagnosis on these specimens, thus proving the Xpert assay as a valuable TB diagnostic tool in supporting conventional histopathological methods. (Source: Tuberculosis)
Source: Tuberculosis - July 3, 2017 Category: Respiratory Medicine Authors: Laura Rindi, Greta Al ì, Barbara Fabiani, Gabriella Fontanini, Carlo Garzelli Source Type: research
Enabling faster Go/No-Go decisions through secondary screens in anti-mycobacterial drug discovery
Management of tuberculosis, already a global health emergency, is becoming increasingly challenging with extensive misuse of second line drugs and their inaccessibility to eighty percent of the eligible patients. Rising statistics of antimicrobial resistance underscores the need for a set of completely new and more effective class of compounds with novel mechanisms of action that can be administered in combination to replace and shorten the present intensive six months regimen. In this review, we stress on the importance and the successes of phenotypic screening for discovery of anti-mycobacterial compound and discuss the ...
Source: Tuberculosis - June 30, 2017 Category: Respiratory Medicine Authors: Raju Mukherjee, Anup Chandrapal, Mousumi Banerjee Tags: Review Source Type: research
Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in subjects with or without tuberculosis
The QuantiFERON-TB Gold Plus (QFT-Plus) represents the new QuantiFERON-TB Gold In-tube (QFT-GIT) to identify latent tuberculosis infection (LTBI). The main differences is the addition of a new tube containing shorter peptides stimulating CD8 T-cells. Aim of this study is to evaluate the accuracy of QFT-Plus compared with QFT-GIT in a cross sectional study of individuals with or without tuberculosis (TB).We enrolled 179 participants: 19 healthy donors, 58 LTBI, 33 cured TB and 69 active TB. QFT-Plus and QFT-GIT were performed. (Source: Tuberculosis)
Source: Tuberculosis - June 26, 2017 Category: Respiratory Medicine Authors: E. Petruccioli, V. Vanini, T. Chiacchio, G. Cuzzi, D.M. Cirillo, F. Palmieri, G. Ippolito, D. Goletti Source Type: research
Sustained expression of DevR/DosR during long-term hypoxic culture of Mycobacterium tuberculosis
DevR/DosR is a key mediator of ‘dormancy’ adaptation in Mycobacterium tuberculosis in response to gaseous stresses such as hypoxia that inhibit aerobic mode of respiration. In the present study, a temporal analysis over a 1 year period has revealed robust expression of representative DevR regulon genes devR, hspX and tgs1, du ring long-term ‘dormancy’ adaptation to hypoxia. Notably, a predominant proportion of long-term hypoxia-adapted bacteria were characterized by their inability to grow on solid media, accumulation of triacylglycerols and recovery of growth in liquid media. (Source: Tuberculosis)
Source: Tuberculosis - June 26, 2017 Category: Respiratory Medicine Authors: Priyanka Kumari, Kriti Sikri, Kohinoor Kaur, Umesh Datta Gupta, Jaya Sivaswami Tyagi Source Type: research
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(Source: Tuberculosis)
Source: Tuberculosis - June 13, 2017 Category: Respiratory Medicine Source Type: research
Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression
Tuberculosis (TB) occurs in only 3 –10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved rem ain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. (Source: Tuberculosis)
Source: Tuberculosis - June 7, 2017 Category: Respiratory Medicine Authors: Mariateresa Coppola, Leonar Arroyo, Krista E. van Meijgaarden, Kees LMC. Franken, Annemieke Geluk, Luis F. Barrera, Tom H.M. Ottenhoff Source Type: research
Host genetics in susceptibility to and severity of mycobacterial diseases
The genetic analysis of susceptibility to infections has proven to be extremely useful for identification of key cells, molecules, pathways, and genes involved in the battle between two genomes – the essence of the infectious process. This is particularly true for tuberculosis and other mycobacterial infections which traditionally attracted much attention from both immunologists and geneticists. In this short review, we observe results of genetic studies performed in human populations an d in animal models and compare relative input of forward and reverse genetic approaches in our knowledge about genetic control of and i...
Source: Tuberculosis - May 27, 2017 Category: Respiratory Medicine Authors: A.S. Apt, N.N. Logunova, T.K. Kondratieva Tags: Review Source Type: research
Mycobacterium tuberculosis MymA is a TLR2 agonist that activate macrophages and a TH1 response
In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) enga gement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR. (Source: Tuberculosis)
Source: Tuberculosis - May 25, 2017 Category: Respiratory Medicine Authors: Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma Source Type: research
Mycobacterium tuberculosis MymA is a TLR2 agonist that activate macrophages and a Thl response
In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engag ement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR. (Source: Tuberculosis)
Source: Tuberculosis - May 25, 2017 Category: Respiratory Medicine Authors: Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma Source Type: research
Evaluation of 24-locus MIRU-VNTR genotyping in Mycobacterium tuberculosis cluster investigations in four jurisdictions in the United States, 2006 –2010
The U.S. Centers for Disease Control and Prevention (CDC) uses a combination of spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) analyses as part of the National TB Genotyping Service (NTGS). The NTGS expansion from 12-locus MIRU-VNTR (MIRU12) to 24-locus MIRU-VNTR (MIRU24) in 2009 enhanced the ability to discriminate Mycobacterium tuberculosis strains. In the current study, we investigated the MIRU24 concordance among epidemiologic-linked tuberculosis (TB) patients in four U.S. (Source: Tuberculosis)
Source: Tuberculosis - May 25, 2017 Category: Respiratory Medicine Authors: Larry D. Teeter, J. Steven Kammerer, Smita Ghosh, Duc T.M. Nguyen, Padmaja Vempaty, Jane Tapia, Roque Miramontes, Wendy A. Cronin, Edward A. Graviss, Tuberculosis Epidemiologic Studies Consortium Tags: Epidemiology Source Type: research
Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model
The aim of the study is to compare counting of colony forming units (CFU), the time to positivity (TTP) assay and the molecular bacterial load (MBL) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. CFU counting, TTP and the MBL assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. Mice were treated for 24 weeks with 4 treatment arms: isoniazid (H) - rifampicin (R) - pyrazinamide (Z), HRZ-Streptomycin (S), HRZ – ethambutol (E) or ZES. (Source: Tuberculosis)
Source: Tuberculosis - May 8, 2017 Category: Respiratory Medicine Authors: Gerjo J. de Knegt, Laura Dickinson, Henry Pertinez, Dimitrios Evangelopoulos, Timothy D. McHugh, Irma A.J.M. Bakker-Woudenberg, Gerry R. Davies, Jurriaan E.M. de Steenwinkel Source Type: research
