TY - JOUR. T1 - Comparative analysis of B- and T-cell epitopes of Mycobacterium leprae and Mycobacterium tuberculosis culture filtrate protein 10. AU - Spencer, John S.. AU - Kim, Hee Jin. AU - Marques, Angela M.. AU - Gonzalez-Juarerro, Mercedes. AU - Lima, Monica C.B.S.. AU - Vissa, Varalakshmi D.. AU - Truman, Richard W.. AU - Gennaro, Maria Laura. AU - Cho, Sang Nae. AU - Cole, Stewart T.. AU - Brennan, Patrick J.. PY - 2004/6. Y1 - 2004/6. N2 - Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against ...
Global Markets Directs, Mycobacterium tuberculosis Protein Ag85A - Pipeline Review, H2 2016, provides in depth analysis on Mycobacterium tuberculosis Protein Ag85A targeted pipeline therapeutics.. The report provides comprehensive information on the Mycobacterium tuberculosis Protein Ag85A, targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in Mycobacterium tuberculosis Protein Ag85A targeted therapeutics development and features dormant and discontinued projects.. Access Full Report with TOC @ http://www.radiantinsights.com/research/mycobacterium-tuberculosis-protein-ag85a-pipeline-review-h2-2016. Global Markets Directs report features investigational ...
TY - JOUR. T1 - Vaccine efficacy of a lysine auxotroph of Mycobacterium tuberculosis. AU - Pavelka, Martin S.. AU - Chen, Bing. AU - Kelley, Cynthia L.. AU - Collins, Frank M.. AU - Jacobs, William R.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2003/7/1. Y1 - 2003/7/1. N2 - The in vivo growth phenotype and vaccine efficacy of a lysine auxotrophic mutant of Mycobacterium tuberculosis strain H37Rv are described. An immunization experiment using a mouse model with an aerosol challenge showed that two doses of the M. tuberculosis mutant were required to generate protection equivalent to that of the Mycobacterium bovis BCG vaccine.. AB - The in vivo growth phenotype and vaccine efficacy of a lysine auxotrophic mutant of Mycobacterium tuberculosis strain H37Rv are described. An immunization experiment using a mouse model with an aerosol challenge showed that two doses of the M. tuberculosis mutant were required to generate protection equivalent to that of the ...
TY - JOUR. T1 - Production of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall in aerosol murine models of tuberculosis. AU - Cardona, P. J.. AU - Julián, E.. AU - Vallès, X.. AU - Gordillo, S.. AU - Muñoz, M.. AU - Luquin, M.. AU - Ausina, V.. PY - 2002/5/30. Y1 - 2002/5/30. N2 - Evolution of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall has been studied for the first time in experimental murine models of tuberculosis induced by aerosol, in which infection, reinfection, reactivation, prophylaxis and treatment with antibiotics have been assayed. Results show a significant humeral response against these antigens, where diacyltrehaleses (DAT) and sulphelipid I (SL-I) elicited higher antibody levels than protein antigens like antigen 85 protein complex (Ag85), culture filtrate proteins (CFP) and purified protein derivative (PPD). Only immunoglobulin M (IgM) antibodies have been detected against DAT and SL-I. Their evolution has a ...
Beijing strains are speculated to have a selective advantage over other Mycobacterium tuberculosis strains because of increased transmissibility and virulence. In Alberta, a province of Canada that receives a large number of immigrants, we conducted a population-based study to determine whether Beijing strains were associated with increased transmission leading to disease compared with non-Beijing strains. Beijing strains accounted for 258 (19%) of 1,379 pulmonary tuberculosis cases in 1991-2007; overall, 21% of Beijing cases and 37% of non-Beijing cases were associated with transmission clusters. Beijing index cases had significantly fewer secondary cases within 2 years than did non-Beijing cases, but this difference disappeared after adjustment for demographic characteristics, infectiousness, and M. tuberculosis lineage. In a province that has effective tuberculosis control, transmission of Beijing strains posed no more of a public health threat than did non-Beijing strains ...
TY - JOUR. T1 - Modeling Host-Pathogen Interaction to Elucidate the Metabolic Drug Response of Intracellular Mycobacterium tuberculosis. AU - Rienksma, Rienk A.. AU - Schaap, Peter J.. AU - Martins Dos Santos, Vitor A.P.. AU - Suarez-Diez, Maria. PY - 2019/5/8. Y1 - 2019/5/8. N2 - Little is known about the metabolic state of Mycobacterium tuberculosis (Mtb) inside the phagosome, a compartment inside phagocytes for killing pathogens and other foreign substances. We have developed a combined model of Mtb and human metabolism, sMtb-RECON and used this model to predict the metabolic state of Mtb during infection of the host. Amino acids are predicted to be used for energy production as well as biomass formation. Subsequently we assessed the effect of increasing dosages of drugs targeting metabolism on the metabolic state of the pathogen and predict resulting metabolic adaptations and flux rerouting through various pathways. In particular, the TCA cycle becomes more important upon drug application, ...
HIV coinfection is the greatest risk factor for transition of latent Mycobacterium tuberculosis infection into active tuberculosis (TB). Epidemiological data reveal both the reduction and the impairment of M. tuberculosis-specific CD4 T cells, although the cellular link and actual mechanisms resulting in immune impairment/suppression need further characterization. M. tuberculosis-specific CD4 T cells play a central role in development of protective immunity against TB, in which they participate in the activation of macrophages through the dendritic cell (DC)-T cell axis. Using an in vitro priming system for generating Ag-specific T cells, we explored if HIV-M. tuberculosis-infected (coinfected) human DCs can dysregulate the M. tuberculosis-specific CD4 T cell phenotype and functionality and subsequently mediate the failure to control M. tuberculosis infection in macrophages. After coculture with coinfected DCs, M. tuberculosis Ag-specific CD4 T cells lost their ability to enhance control of M. ...
Purified Recombinant Mycobacterium Tuberculosis ADK Protein (1-181 aa), His-SUMO-tagged from Creative Biomart. Recombinant Mycobacterium Tuberculosis ADK Protein (1-181 aa), His-SUMO-tagged can be used for research.
Fingerprint Dive into the research topics of Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. Together they form a unique fingerprint. ...
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Tuberculosis (TB) is a disease caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. Tuberculous arthritis caused by Mycobacterium tuberculosis also has been described. The joints most frequently involved are the spine, hips, knees, wrists, and ankles. Valvular endocarditis due to Mycobacterium tuberculosis also has been reported. If not treated properly, TB disease can be fatal. VetPCR TBC Detection Kit is the direct detection of Mycobacterium tuberculosis on the basis of a genetic database, so it can diagnose very fast and accurately. It can amplify only specific gene using the PCR (Polymerase Chain Reaction) method, and take only 3 hours for detection. Therefore, it is a very fast, accurate and reliable technique.
TY - JOUR. T1 - Secreted immunodominant Mycobacterium tuberculosis antigens are processed by the cytosolic pathway. AU - Grotzke, Jeff E.. AU - Siler, Anne C.. AU - Lewinsohn, Deborah A.. AU - Lewinsohn, David M.. PY - 2010/10/1. Y1 - 2010/10/1. N2 - Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic infection in most individuals. Although CD8+ T cells are elicited at high frequencies over the course of infection in both humans and mice, how phagosomal M. tuberculosis Ags are processed and presented by MHC class I molecules is poorly understood. Broadly, both cytosolic and noncytosolic pathways have been described. We have previously characterized the presentation of three HLA-I epitopes from M. tuberculosis and shown that these Ags are processed in the cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. In this paper, we now characterize the processing pathway ...
To determine differences in the ability of Mycobacterium tuberculosis strains to withstand antituberculosis drug treatment, we compared the activity of antituberculosis drugs against susceptible Beijing and East-African/Indian genotype M. tuberculosis strains. Beijing genotype strains showed high rates of mutation within a wide range of drug concentrations, possibly explaining this genotypes association with multidrug-resistant tuberculosis.
Advantages of sSNP genotyping: sSNPs afford many advantages for analysis of phylogenetic relationships among microbial strains, especially closely related clonal organisms such as the M. tuberculosis complex. Most or all sSNPs are selectively neutral and hence minimally subject to convergence, a process that can obscure or distort evolutionary relationships (Kimura 1983). Binary data are obtained, which means that the information is readily amenable to storage, retrieval, analysis by personal computers equipped with simple software, and comparison between different laboratories and studies. Importantly, the considerable biomedical interest in human SNPs (Schorket al. 2000; Dalyet al. 2001; Gut 2001; Johnsonet al. 2001) means that microbial pathogen research will benefit extensively from the ongoing development and implementation of methods to index very large numbers of SNPs efficiently, inexpensively, and automatically (Kwok 2001). Because of the many advantages of using sSNP analysis for ...
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Background: The risk of encountering tuberculosis (TB) has reduced with the decreased incidence of the disease; however, it still can be found at autopsy.. Aim: To assess the magnitude of exposure to Mycobacterium tuberculosis at autopsy in a large general hospital setting, in a country with low incidence.. Methods: Retrospective search of the autopsy records from 1991 to 2004. Patients records and histological slides were reviewed, and medical personnel interviewed.. Results: 15 cases of active TB were identified in the 14-year period, during which 4930 autopsies were performed (1 case per 329 autopsies); of these, 10 cases were unsuspected (67%). Five of these cases contained abundant acid-fast bacilli. Patients tended to be middle aged and males with complex clinical histories; two were HIV positive. Two patients were brought in dead to hospital, with no clinical indication of TB. Of 15 autopsy staff, 1 required chemoprophylaxis but none contracted TB.. Conclusion: The risk of unexpectedly ...
Early detection of resistance to second-line anti-tuberculosis drugs is important for the management of multidrug-resistant (MDR)-TB. The Genotype® MTBDRsl VERSION 2.0 (VER 2.0) line probe assay has been redesigned for molecular detection of resistance-conferring mutations of fluoroquinolones (FLQ) (gyrA and gyrB genes) and second-line injectable drugs (SLID) (rrs and eis genes). The study evaluated the diagnostic performance of MTBDRsl VER 2.0 for the detection of second-line drug resistance compared with phenotypic drug susceptibility testing (DST), using the Bactec™ MGIT 960 system on Mycobacterium tuberculosis complex isolates from South Africa. A total of 268 repository isolates collected between 2012 and 2014, with rifampicin -mono-resistant (RR) or MDR based on DST were selected. MTBDRsl VER 2.0 testing was performed on these isolates and results analysed. The MTBDRsl VER 2.0 sensitivity and specificity indices for culture isolates were; FLQ 100% (95% CI, 95.8-100%) ; 98.9% (95% CI, ...
PhD Project - Protein kinases and nitric oxide in the stealthy survival of Mycobacterium tuberculosis at University of Leicester, listed on FindAPhD.com
Mouse serum raised against killed antigen preparations of Mycobacterium tuberculosis failed to recognize most of the recombinant antigens of M. tuberculosis that were originally identified by reactivity to tuberculosis (TB) patient sera. Similar results were obtained with serum from guinea pigs immunized with live and killed mycobacteria. Antibodies raised against seven random TB patient serum-reactive antigens detected each of these antigens in the sonicate preparation. The nucleotide sequences of the genes for these seven antigens revealed that all represented hitherto unreported genes of M. tuberculosis. Our results suggest differential presentation to the host immune system of the same antigens derived from live and killed mycobacteria.. ...
Signs of Mycobacterium Tuberculosis, Susceptibility to, X-linked including medical signs and symptoms of Mycobacterium Tuberculosis, Susceptibility to, X-linked, symptoms, misdiagnosis, tests, common medical issues, duration, and the correct diagnosis for Mycobacterium Tuberculosis, Susceptibility to, X-linked signs or Mycobacterium Tuberculosis, Susceptibility to, X-linked symptoms.
Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the ...
BioAssay record AID 1084878 submitted by ChEMBL: Antitubercular activity against multidrug-resistant Mycobacterium tuberculosis by NCCLS agar dilution method.
Massachusetts was one of seven sentinel surveillance sites in the National Tuberculosis Genotyping and Surveillance Network. From 1996 through 2000, isolates from new patients with tuberculosis (TB) underwent genotyping. We describe the impact that genotyping had on public health practice in Massachusetts and some limitations of the technique. Through genotyping, we explored the dynamics of TB outbreaks, investigated laboratory cross-contamination, and identified Mycobacterium tuberculosis strains, transmission sites, and accurate epidemiologic links. Genotyping should be used with epidemiologic follow-up to identify how resources can best be allocated to investigate genotypic findings.
BioAssay record AID 245416 submitted by ChEMBL: Minimum inhibitory concentration against resistant Mycobacterium tuberculosis clinical isolates; N=9; Range=8-16.
Mycobacterium tuberculosis ATCC ® 25177D-5™ Designation: Genomic DNA from Mycobacterium tuberculosis Strain H37Ra TypeStrain=False Application: Respiratory research
Reversible protein phosphorylation, regulated by protein kinases and phosphatases, mediates a switch between protein activity and cellular pathways that contribute to a large number of cellular processes. The Mycobacterium tuberculosis genome encodes 11 Serine/Threonine kinases (STPKs) which show close homology to eukaryotic kinases. This study aimed to elucidate the phosphoproteomic landscape of a clinical isolate of M. tuberculosis. We performed a high throughput mass spectrometric analysis of proteins extracted from an early-logarithmic phase culture. Whole cell lysate proteins were processed using the filter-aided sample preparation method, followed by phosphopeptide enrichment of tryptic peptides by strong cation exchange (SCX) and Titanium dioxide (TiO2) chromatography. The MaxQuant quantitative proteomics software package was used for protein identification. Our analysis identified 414 serine/threonine/tyrosine phosphorylated sites, with a distribution of S/T/Y sites; 38% on serine, 59% on
Data on the levels of resistance of Mycobacterium tuberculosis complex (MTBC) strains to first line anti-tuberculosis drugs in Cameroon, and on the species of MTBC circulating in the country are obsolete. The picture about 10 years after the last studies, and 6 years after the re-organisation of the National Tuberculosis (TB) Control Programme (NTBCP) is not known. The study was conducted from February to July 2009 in the West and Centre regions of Cameroon. A total of 756 suspected patients were studied. MTBC species were detected by the standard Ziehl-Neelsen staining method. Bacterial susceptibility to the first line drugs [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM)] were performed on cultures using the indirect proportion method. MTBC species were identified by standard biochemical and culture methods. Of the 756 suspected patients, 154 (20.37%) were positive by smear microscopy. Of these, 20.77% were HIV patients. The growth of Mycobacterium was observed with the
Metabolomics and stable isotope labelling studies of virulent Mycobacterium tuberculosis reveal a de-centralised metabolic network able to utilise various amino acids as nitrogen sources to a better extent than ammonium.
3550 NIEMANN ET AL. J. CLIN. MICROBIOL. 5. Cohen, T., and M. Murray. 2004. Modeling epidemics of multidrug-resistant 23. Mokrousov, I., T. Otten, B. Vyshnevskiy, and O. Narvskaya. 2002. Detection Mycobacterium tuberculosis of heterogeneous !tness. Nat. Med. 10:1117- of embB306 mutations in ethambutol-susceptible clinical isolates of Myco- 1121. bacterium tuberculosis from Northwestern Russia: implications for genotypic 6. Comas, I., S. Homolka, S. Niemann, and S. Gagneux. 2009. Genotyping of resistance testing. J. Clin. Microbiol. 40:3810-3813. genetically monomorphic bacteria: DNA sequencing in mycobacterium tu- 24. Mokrousov, I., T. Otten, T. Zozio, E. Turkin, V. Nazemtseva, A. Sheremet, B. berculosis highlights the limitations of current methodologies. PLoS One Vishnevsky, O. Narvskaya, and N. Rastogi. 2009. At Baltic crossroads: a 4:e7815. molecular snapshot of Mycobacterium tuberculosis population diversity in 7. Cox, H. S., S. Kalon, S. Allamuratova, V. Sizaire, Z. N. Tigay, S. Rusch- ...
BACKGROUND: Peru holds the fourth highest burden of tuberculosis in the Americas. Despite an apparently well-functioning DOTS control program, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase. To worsen this situation, cases of extensively drug resistance tuberculosis (XDR-TB) have been detected. Little information exists about the genetic diversity of drug-susceptible vs. MDR-TB and XDR-TB. METHODS: Cryopreserved samples of XDR strains from 2007 to 2009 (second semester), were identified and collected. Starting from 227 frozen samples, a total of 142 XDR-TB strains of Mycobacterium tuberculosis complex (MTBC; 1 isolate per patient) were retained for this study. Each strain DNA was analyzed by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU-15). RESULTS: Among the 142 isolates analyzed, only 2 samples (1.41%) could not be matched to any lineage. The most prevalent sublineage was Haarlem (43.66%), followed by T (27.46%), LAM (16.2%),
TY - JOUR. T1 - The temporal expression profile of Mycobacterium tuberculosis infection in mice. AU - Talaat, Adel M.. AU - Lyons, Rick. AU - Howard, Susan T.. AU - Johnston, Stephen Albert. PY - 2004/3/30. Y1 - 2004/3/30. N2 - Infection with Mycobacterium tuberculosis causes the illness tuberculosis with an annual mortality of ≈2 million. Understanding the nature of the host-pathogen interactions at different stages of tuberculosis is central to new strategies for developing chemotherapies and vaccines. Toward this end, we adapted microarray technology to analyze the change in gene expression profiles of M. tuberculosis during infection in mice. This protocol provides the transcription profile of genes expressed during the course of early tuberculosis in immune-competent (BALB/c) and severe combined immune-deficient (SCID) hosts in comparison with growth in medium. The microarray analysis revealed clusters of genes that changed their transcription levels exclusively in the lungs of BALB/c, ...
Phagocytosis of tubercle bacilli by antigen-presenting cells in human lung alveoli initiates a complex infection process by |i|Mycobacterium tuberculosis|/i| and a potentially protective immune response by the host. |i|M. tuberculosis|/i| has devoted a large part of its genome towards functions that allow it to successfully establish latent or progressive infection in the majority of infected individuals. The failure of immune-mediated clearance is due to multiple strategies adopted by |i|M. tuberculosis|/i| that blunt the microbicidal mechanisms of infected immune cells and formation of distinct granulomatous lesions that differ in their ability to support or suppress the persistence of viable |i|M. tuberculosis|/i|. In this paper, current understanding of various immune processes that lead to the establishment of latent |i|M. tuberculosis|/i| infection, bacterial spreading, persistence, reactivation, and waning or elimination of latent infection as well as new diagnostic approaches being used for
Spontaneous phthiocerol dimycocerosate-deficient variants of Mycobacterium tuberculosis are susceptible to gamma interferon-mediated immunity Academic Article ...
Rapid and accurate detection of Mycobacterium tuberculosis complex (MTBc) is a key aspect of effective tuberculosis treatment and control. The Amplified Mycobacterium tuberculosis complex Direct Test (Gen-Probe) utilizes transcription mediated amplification to detect MTB complex ribosomal RNA. This test is very sensitive, specific, and can be performed within 5 hours. Although it does not differentiate among members of the MTB complex, i.e., M. tuberculosis, M. bovis, M. bovis BCG, M africanum, and M. microti , the isolation of the last 4 organisms is very rare.. The test is currently approved by FDA for AFB smear-positive respiratory specimens from untreated patients (sensitivity = 98%, specificity = 96.8%). However, studies have shown that it will also benefit patients with high suspicion of tuberculosis, but with negative AFB smear results. A positive result is strongly suggestive for the diagnosis of tuberculosis if the clinical history and radiographic finding are consistent. This test ...
Abstract. Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11-71.4, P | 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12-2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection in children
We performed spoligotyping on 114 strains of the Mycobacterium tuberculosis (Mtb) complex that had been isolated from patients in Minas Gerais Health Units
Worldwide, there are nearly 10 million new cases of active TB and 1.8 million associated deaths every year. WHO estimates that one-third of the worlds population is infected with Mycobacterium tuberculosis (Mtb), forming a huge latent Mtb global reservoir. This renders the prospect of ever eliminating Mtb from the human race almost impossible. Several controversial issues regarding host-pathogen interactions and existing prevention and eradication strategies for latent Mtb infections need to be critically re-examined. In this viewpoint, widely held assumptions on Mtb latency and isoniazid monotherapy and chemoprophylaxis are challenged. We highlight the need for future research to resolve these issues and to develop evidence-based strategies for better understanding of equilibrium and escape of Mtb in the human body, eventually leading to global recommendations for elimination of the latent Mtb state through informed policy and practice. Until such strategies and policies are realized, WHO and ...
Immunologist Johan Van Weyenbergh (KU Leuven) and his Belgian-Brazilian colleagues have shown that a drug used to fight arthritis also stops the process that allows the tuberculosis bacillus to infect and hijack blood stem cells.. Tuberculosis (TB) may affect any part of the body, but the spread of the disease might start in the bone marrow. Immunologists from KU Leuven and Brazil have shown that the TB bacillus hijacks the blood stem cells from the bone marrow to turn them into ideal host cells for multiplication. They also found that this mechanism can be stopped by administering an anti-arthritis drug.. Hiding in the bone marrow. About a quarter of the world population is a carrier of Kochs bacillus, which can cause tuberculosis (TB). Most people who are infected have latent tuberculosis, meaning that they dont become ill. However, this latent TB can turn into active tuberculosis when the immune system becomes weaker, for instance in the elderly or in HIV patients. Worldwide, TB claims more ...
TY - JOUR. T1 - Evaluation of the TB Ag MPT64 rapid test for the identification of Mycobacterium tuberculosis complex. AU - Martin, A. AU - Bombeeck, D. AU - Mulders, W. AU - Fissette, K. AU - De Rijk, P. AU - Palomino, JC. N1 - PPU; ITG-M1A; ITG-M2B; ITG-M3B; ITG-M4B; ITG-M5B; ITG-MLA; MICRO; U-MYCOB; JIF; PDF; DSPACE. PY - 2011. Y1 - 2011. KW - B780-tropical-medicine. KW - Bacterial diseases. KW - Tuberculosis. KW - Mycobacterium tuberculosis complex. KW - Evaluation. KW - Performance. KW - Rapid diagnostic tests. KW - Identification. KW - Drug resistance. KW - Nitrate reductase assay. KW - Sensitivity. KW - Specificity. KW - Laboratory techniques and procedures. U2 - 10.5588/ijtld.10.0474. DO - 10.5588/ijtld.10.0474. M3 - A1: Web of Science-article. C2 - 21756526. VL - 15. SP - 703. EP - 705. JO - International Journal of Tuberculosis and Lung Disease. JF - International Journal of Tuberculosis and Lung Disease. SN - 1027-3719. IS - 5. ER - ...
Pulmonary and pleural fibrosis is one of pathological characterized by Mycobacterium tuberculosis (M. tb) infection in the lungs. When the lungs are infected with M. tb, the recruitment of immune cells and fibroblasts leads to granuloma formation and fibrotic scaring in interstitial lung tissue, which in turns causes irreversible loss of pulmonary function and pulmonary failure. Several studies indicated that the fibrotic factors, such as transforming growth factor- (TGF-), were increased in pleural effusion and serum of patient with tuberculosis. The expression of connective tissue growth factor (CTGF), a fibrotic factor, has been reported in lung fibrosis. However, the mechanism of M. tb-induced CTGF expression in human lung fibroblasts is still unclear. Fibrocytes are unique bone marrow-derived mesenchymal progenitor cells found in circulation. Fibrocytes have been shown to play an important role in wound healing following injury and in the generation of pulmonary fibrosis. Previous ...
One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis We performed a phase I randomized controlled trial of isoniazid preventive therapy (IPT) before revaccination with bacillus Calmette-Guérin (BCG) in healthy, tuberculin skin test-positive (≥15-mm induration), HIV-negative South African adults. We hypothesized that preclearance of latent bacilli with IPT modulates BCG immunogenicity following revaccination. Frequencies and coexpression of IFN-γ, TNF-α, IL-2, IL-17, and/or IL-22 in CD4 T cells and IFN-γ-expressing CD8 T, γδ T, CD3(+)CD56(+) NKT-like, and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were revaccinated with BCG after IPT (n = 33) or without prior IPT (n = 39). IPT had little effect on frequencies or cytokine coexpression patterns of M. tuberculosis- or BCG-specific responses. Revaccination transiently boosted BCG-specific Th1 ...
Tuberculosis remains a serious threat to human health as an infectious disease in China. Henan, a most populated province in China, has a high incidence of tuberculosis (TB). Though the genetic diversity of Mycobacterium tuberculosis (MTB) has been investigated in many regions, there have been only a few studies on the molecular characteristics and drug resistance phenotypes in Henan. This is the first study on the genetic profile of MTB from Henan. A total of 668 MTB isolates from various areas were genotyped with spoligotyping and 26-locus MIRU-VNTR (classical 24-locus MIRU-VNTR and 2 other loci). The association between TB spoligotype signatures and drug-resistant profiles was analysed. Our data revealed that MTB isolates circulating in Henan had a high degree of genetic variation. The Beijing family was the most predominant genotype (83.53%,n = 558), and the typical Beijing type(ST1) was the major sublineage (81.73%,n = 546). In total,668 isolates were divided into 567 different types, forming 38
In this study, Mycobacterium tuberculosis complex was detected by BD ProbeTec ET system in 4716 respiratory and 167 nonrespiratory samples [mostly (98%) smear negative]. Sensitivity, specificity, positive and negative predictive values were 81.8%, 98.3, 85.1 and 97.9 for respiratory and 100%, 96.2, 64.7 and 100, for nonrespiratory samples, respectively. Among 149 (3.1%) ProbeTec DTB positive and culture negative samples, 72 (65 respiratory and seven nonrespiratory) (48.3%) were recovered from the patients who were evaluated as having TB infection. The system has been found as useful in early diagnosis of tuberculosis infection in association with the clinical, radiological and histopathological findings.. Key words: BD ProbeTec ET, extrapulmonary, molecular detection, pulmonary, tuberculosis. According to the World Health Organization (WHO), tuberculosis (TB) has been still an important problem all over world (WHO, 2013a). The definitive TB diagnosis depends on the results of microbiological ...
In 1947 Dubos and Middlebrook formulated a media (7H9) containing albumin and oleic acid which enhanced the growth of tubercle bacilli, and protected the organisms against a variety of toxic agents. (5) Later, in 1958, Middlebrook and Cohn improved this first formulation and developed a media (7H10) which allowed more luxuriant, faster growth of Mycobacterium species. (9) Cohn, in 1968, incorporated casein hydrolysate into the 7H10 medium, and obtained a media that stimulated the growth of mycobacteria that would not otherwise grow on the 7H10 medium. This formulation was then designated 7H11 Agar, and is recommended over 7H10 Agar. (4,7) Middlebrook 7H11 Agar contains inorganic compounds that supply essential growth stimulating inorganic salts as well as vitamins and necessary co-factors. Glycerol is provided as a source of carbon and energy for the tubercle organisms. Sodium citrate is converted to citric acid, which holds the inorganic cations in solution. Casein hydrolysate is incorporated ...
Title:Mycobacterial tuberculosis Enzyme Targets and their Inhibitors. VOLUME: 19 ISSUE: 5. Author(s):Anil Kumar Saxena* and Anamika Singh. Affiliation:Division of Medicinal and Process Chemistry, CSIR Central Drug Research Institute, Lucknow 226 001, Division of Medicinal and Process Chemistry, CSIR Central Drug Research Institute, Lucknow 226 001. Keywords:Mycobacterium tuberculosis, Enzyme targets, Inhibitors, Minimum inhibitory concentration (MIC), Tuberculosis (TB), ATP.. Abstract:Tuberculosis (TB) still continues to be a major killer disease worldwide. Unlike other bacteria Mycobacterium tuberculosis (Mtb) has the ability to become dormant within the host and to develop resistance. Hence efforts are being made to overcome these problems by searching for new antitubercular agents which may be useful in the treatment of multidrug-(MDR) and extensively drugresistant (XDR) M. tuberculosis and shortening the treatment time. The recent introduction of bedaquiline to treat MDR-TB and XDR-TB may ...
BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data.
HIV coinfection is the greatest risk factor for transition of latent Mycobacterium tuberculosis infection into active tuberculosis (TB). Epidemiological data reveal both the reduction and the impairment of M. tuberculosis-specific CD4 T cells, although the cellular link and actual mechanisms resulting in immune impairment/suppression need further characterization. M. tuberculosis-specific CD4 T cells play a central role in development of protective immunity against TB, in which they participate in the activation of macrophages through the dendritic cell (DC)-T cell axis. Using an in vitro priming system for generating Ag-specific T cells, we explored if HIV-M. tuberculosis-infected (coinfected) human DCs can dysregulate the M. tuberculosis-specific CD4 T cell phenotype and functionality and subsequently mediate the failure to control M. tuberculosis infection in macrophages. After coculture with coinfected DCs, M. tuberculosis Ag-specific CD4 T cells lost their ability to enhance control of M. ...
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A new, simple immunochromatographic assay for rapid identification of Mycobacterium tuberculosis complex in liquid cultures has been developed. The principle of the assay is binding of the Mycobacterium tuberculosis complex specific antigen to the monoclonal antibody conjugated on the test strip. The aim of this study is evaluation of the performance of immunochromatographic assay in identification of Mycobacterium tuberculosis complex in primary positive liquid cultures of BacT/Alert automated system.. A total of 159 primary positive liquid cultures were tested using the immunochromatographic assay (BD MGIT TBc ID) and the conventional subculture, followed by identification using biochemical tests.. Of 159 positive liquid cultures, using the conventional method, Mycobacterium tuberculos is was identified in 119 (74.8%), nontuberculous mycobacteria were found in 4 (2.5%), 14 (8.8%) cultures were contaminated and 22 (13.8%) cultures were found to be negative. Using the immunochromatographic ...
TY - JOUR. T1 - Peptides derived from Mycobacterium tuberculosis Rv2301 protein are involved in invasion to human epithelial cells and macrophages. AU - Ocampo, M.. AU - Rodríguez, D. M.. AU - Curtidor, H.. AU - Vanegas, M.. AU - Patarroyo, M. E.. AU - Patarroyo, M. E.. N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2012/6. Y1 - 2012/6. N2 - The specific function of putative cut2 protein (or CFP25), encoded by the Rv2301 gene from Mycobacterium tuberculosis H37Rv, has not been identified yet. The aim of this study was to assess some of CFP25 characteristics and its possible biological role in Mycobacterium tuberculosis H37Rv invasion process to target cells. Molecular assays indicated that the gene encoding Rv2301 is present and transcribed in M. tuberculosis complex strains. The presence of Rv2301 protein over the bacilli surface was confirmed by Western blot and immunoelectron microscopy analyses, using goats sera inoculated with synthetic peptides derived from ...
Background: Accurate active tuberculosis (TB) diagnosis remains a challenge in clinical practice, especially in HIV infected patients. The aim of the study was to determine the serum markers that are associated with pulmonary Mycobacterium tuberculosis among HIV infected febrile individuals. Methods: The study compared HIV infected people with and without pulmonary tuberculosis and asymptomatic HIV infected individuals for inflammatory makers CRP and leptin levels, and the activation markers IP 10 and β2 microglobulin. Markers were tested on previously collected frozen serum samples. Serum markers CRP, Leptin and β2- microglobulin were measured using the enzyme-linked immunosorbent assays in 20 cases with pulmonary Mycobacterium tuberculosis, 20 suspects (control1) with B symptoms but without Mycobacterium tuberculosis and 20 (control 2) asymptomatic HIV infected individuals. The IP 10 was measured using the Bio-plex Pro assay. The assays were performed according to the manufacturers‟ ...
Sarcoidosis is a granulomatous disorder of unknown cause that affects multiple organs. The cells of the granuloma are organized spatially as immune granulomas, the characteristic of sarcoidosis, as a result of an immunological response to an antigenic trigger. It has been suggested that infective agents, including mycobacteria, propionibacteria, parasites such as Schistosoma, and fungi such as Coccidioides, are likely triggers (but not as infection) in a genetically predisposed individual and that this initial event leads to the sarcoidosis granulomatous response (2). Other agents such as beryllium, zirconium, and aluminum can also trigger the granulomatous response (2). Most studies of a possible causal organism have focused on mycobacteria (8), but a convincing association between sarcoidosis and mycobacterial infections has yet to be established. Recently, using PCR techniques based on IS6110, MPB64, and mtp-40 amplification, we reported the presence of Mycobacterium tuberculosis complex ...
TY - JOUR. T1 - Stable isoniazid derivatives. T2 - In silico studies, synthesis and biological assessment against mycobacterium tuberculosis in liquid culture. AU - Gaonkar, S. L.. AU - Hakkimane, S. S.. AU - Bharath, B. R.. AU - Shenoy, V. P.. AU - Vignesh, U. N.. AU - Guru, B. R.. PY - 2020. Y1 - 2020. N2 - Isoniazid (INH) is well-known as a crucial drug in all multiple drug treatment for tuberculosis (TB) as approved by the WHO. It is a small molecule and highly hydrophilic, has low cellular penetration. By modifying highly hydrophilic drugs into hydrophobic will help in enhancing the cellular penetration of the drug and this, in turn, improves the therapeutic efficacy of the drug. Isoniazid a prodrug gets activated by KatG enzyme of Mycobacterium tuberculosis thus inhibiting InhA enzyme essential for the synthesis of Mycolic acid, a chief component of Mycobacterium tuberculosis cell wall. Hence in the current study, a series of isoniazid hydrazones are designed where Isoniazid can be ...
TY - JOUR. T1 - In vitro effect of three-drug combinations of antituberculous agents against multidrug-resistant Mycobacterium tuberculosis isolates. AU - Rey-Jurado, Emma. AU - Tudó, Griselda. AU - De La Bellacasa, Jorge Puig. AU - Espasa, Mateu. AU - González-Martín, Julian. PY - 2013/3/1. Y1 - 2013/3/1. N2 - Multidrug resistance has become a problem in the management of tuberculosis, leading to an urgent need for research related to new regimens including the currently available drugs. The objectives of this study were: (i) to study the effect of the following second-choice three-drug combinations against multidrug-resistant (MDR) and drug-susceptible clinical isolates (levofloxacin, linezolid and ethambutol; levofloxacin, amikacin and ethambutol; and levofloxacin, linezolid and amikacin); and (ii) to compare the effect of these combinations with an isoniazid, rifampicin and ethambutol combination against drug-susceptible clinical isolates. A total of 9 MDR clinical and 12 drug-susceptible ...
TY - JOUR. T1 - Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis. AU - Cerda-Maira, Francisca A.. AU - Pearce, Michael J.. AU - Fuortes, Michele. AU - Bishai, William R.. AU - Hubbard, Stevan R.. AU - Darwin, K. Heran. PY - 2010/9/1. Y1 - 2010/9/1. N2 - Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed pupylation, Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in ...
The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of
Preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination (1,2). Three randomized controlled trials have shown that a new combination regimen of isoniazid (INH) and rifapentine (RPT) administered weekly for 12 weeks as directly observed therapy (DOT) is as effective for preventing TB as other regimens and is more likely to be completed than the U.S. standard regimen of 9 months of INH daily without DOT (2 5). This report provides CDC recommendations for using the INH-RPT regimen. The new regimen is recommended as an equal alternative to the 9-month INH regimen for otherwise healthy patients aged ≥12 years who have LTBI and factors that are predictive of TB developing (e.g., recent exposure to contagious TB). The new regimen also can be considered for other categories of patients when it offers practical advantages. Although the INH-RPT regimen was well tolerated in treatment trials, monitoring for ...
Planktonic cultures of Mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (TB), are highly susceptible to killing by ascorbic acid (vitamin C). As planktonically grown M. tuberculosis are unlikely to be representative of the bacterium during infection, we set out to determine if ascorbic acid was also antibacterial against M. tuberculosis growing as a biofilm. We use biofilm growth as a model for the multiple phenotypic states M. tuberculosis can exist in during an infection. In our experiments we employed bioluminescent M. tuberculosis H37Rv (BSGTB1) in which light production is a non-destructive surrogate measure of bacterial viability. Light levels were monitored before and after treatment with 1mM to 256mM ascorbic acid. After 3 weeks of treatment, biofilms were disrupted, washed and inoculated into fresh media to look for sterilisation. Our findings show that ascorbic acid concentrations of 32mM or greater reduced bioluminescence produced by M. tuberculosis
1. Molecular genetics of Mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide testing by MTBDRsl in Armenia. Authors: Margaryan, H.,Farnia, P.,Hayrapetyan, A.,Mirzoyan, A.. Journal : International Journal of Mycobacteriology. 2. Overview of drug-resistant tuberculosis worldwide. Authors: Velayati, A.A.,Farnia, P.,Farahbod, A.M.. Journal : International Journal of Mycobacteriology. 3. Molecular drug susceptibility testing against the first-line (rifampin and isoniazid) and second-line (ciprofloxacin-amikacin and kanamycin) treatment in different subtypes of Mycobacterium simiae. Authors: Farnia, P., Malekshahian, D., Tabarsi, P., Seif, S., Velayati, AA.,. Journal : International Journal of Mycobacteriology. 4. Deletion of region of difference 181 in Mycobacterium tuberculosis Beijing strains. Authors: Sharifipour, E., Farnia, P., Mozafari, M., Irani, S., Velayati, AA.,. Journal : International Journal of Mycobacteriology. 5. HIV and tuberculosis trends and survival of ...
Rationale: Xpert MTB/RIF is a novel automated molecular diagnostic recently endorsed by the World Health Organization. However, performance-related data from high HIV prevalence settings are limited. Objectives: The impact of sample-related factors on performance and the significance of Xpert MTB/RIF-positive culture-negative discordance remain unclear. Methods: Xpert MTB/RIF was evaluated using single archived spot-sputum samples from 496 South African patients with suspected TB. Mycobacterium tuberculosis culture positivity and phenotypic resistance to rifampicin served as reference standards. Measurements and Main Results: Overall, Xpert MTB/RIF detected 95% (95% confidence interval [CI], 88-98%; 89 of 94) of smear-positive culture-positive cases and the specificity was 94% (91-96%; 320 of 339). The sensitivity in smear-negative cases was 55% (35-73%; 12 of 22) when the analysis was restricted to 1 ml of unprocessed sputum and culture time-to-positivity of less than or equal to 28 days. ...
We reviewed reports of false-positive cultures for Mycobacterium tuberculosis and here propose guidelines for detecting and managing patients with possible false-positive cultures. Mechanisms of false-positive cultures included contamination of clinical devices, clerical errors, and laboratory cross-contamination. False-positive cultures were identified in 13 (93%) of the 14 studies that evaluated ⩾100 patients; the median false-positive rate was 3.1% (interquartile range, 2.2%-10.5%). Of the 236 patients with false-positive cultures reported in sufficient detail, 158 (67%) were treated, some of whom had toxicity from therapy, as well as unnecessary hospitalizations, tests, and contact investigations. Having a single positive culture was a sensitive but nonspecific criterion for detecting false-positive cultures. False-positive cultures for M. tuberculosis are not rare but are infrequently recognized by laboratory and clinical personnel. Laboratories and tuberculosis control programs should ...
ENGLISH ABSTRACT: Central dogma suggests that mutations in target genes is the primary cause of resistance to first and second-line anti-TB drugs in Mycobacterium tuberculosis. However, it was previously reported that approximately 5% of Rifampicin mono-resistant clinical M. tuberculosis did not harbor mutations in the rpoB gene. The present study hypothesized that active efflux plays a contributory role in the level of intrinsic resistance to different anti-TB drugs (Isoniazid, Ethionamide, Pyrazinamide, Ethambutol, Ofloxacin, Moxifloxacin, Ciprofloxacin, Streptomycin, Amikacin and Capreomycin in RIF mono-resistant clinical M. tuberculosis isolates with a rpoB531 (Ser-Leu) mutation. This study aimed to define the role of Efflux pump inhibitors (verapamil, carbonylcyanide m-chlorophenylhydrazone and reserpine) in enhancing the susceptibility to different anti-TB drugs in the RIF mono-resistant clinical isolates. The isolates were characterized by determining the level of intrinsic resistance to ...
TY - JOUR. T1 - Safety and immunogenicity of the Mycobacterium tuberculosis ΔlysA ΔpanCD vaccine in domestic cats infected with feline immunodeficiency virus. AU - Zimmerman, Dawn M.. AU - Waters, W. Ray. AU - Lyashchenko, Konstantin P.. AU - Nonnecke, Brian J.. AU - Armstrong, Douglas L.. AU - Jacobs, William R.. AU - Larsen, Michelle H.. AU - Egan, Erin. AU - Dean, Gregg A.. PY - 2009/3/1. Y1 - 2009/3/1. N2 - Feline immunodeficiency virus (FIV)-positive and FIV-negative cats (n = 4/group) received 2 × 106 CFU Mycobacterium tuberculosis ΔlysA ΔpanCD intramuscularly. Vaccination elicited antibody responses, albeit at lower levels in FIV-positive cats than in FIV-negative cats. Delayed-type hypersensitivity responses were minimal in both groups. No adverse reactions were found.. AB - Feline immunodeficiency virus (FIV)-positive and FIV-negative cats (n = 4/group) received 2 × 106 CFU Mycobacterium tuberculosis ΔlysA ΔpanCD intramuscularly. Vaccination elicited antibody responses, albeit ...
BACKGROUND Early diagnosis of tuberculosis (TB) and identification of strains of Mycobacterium tuberculosis resistant to anti-TB drugs are considered the main factors for disease control.. OBJECTIVES To standardise a real-time polymerase chain reaction (qPCR) assay technique and apply it to identify mutations involved in M. tuberculosis resistance to Isoniazid (INH) directly in Ziehl-Neelsen (ZN) stained slides.. METHODS Were analysed 55 independent DNA samples extracted from clinical isolates of M. tuberculosis by sequencing. For application in TB diagnosis resistance, 59 ZN-stained slides were used. The sensitivity, specificity and Kappa index, with a 95% confidence interval (CI95%), were determined.. FINDINGS The agreement between the tests was, for the katG target, the Kappa index of 0.89 (CI95%: 0.7-1.0). The sensitivity and specificity were 97.6% (CI95%: 87.7-99.9) and 91.7% (CI95%: 61.5-99.5), respectively. For inhA, the Kappa index was 0.92 (CI95%: 0.8-1.0), the sensitivity and ...
Despite the widespread use of the childhood vaccine against tuberculosis (TB), Mycobacterium bovis bacillus Calmette-Guérin (BCG), the disease remains a serious global health problem. A successful vaccine against TB that replaces or boosts BCG would include antigens that induce or recall the appropriate T cell responses. Four Mycobacterium tuberculosis (Mtb) antigens-including members of the virulence factor families PE/PPE and EsX or antigens associated with latency-were produced as a single recombinant fusion protein (ID93). When administered together with the adjuvant GLA-SE, a stable oil-in-water nanoemulsion, the fusion protein was immunogenic in mice, guinea pigs, and cynomolgus monkeys. In mice, this fusion protein-adjuvant combination induced polyfunctional CD4 T helper 1 cell responses characterized by antigen-specific interferon-γ, tumor necrosis factor, and interleukin-2, as well as a reduction in the number of bacteria in the lungs of animals after they were subsequently infected ...
Antibacterial Activity of Aristolochia brevipes against Multidrug-Resistant Mycobacterium tuberculosis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The continuing expansion of Eurasian wild boar (Sus scrofa) populations raises concerns regarding disease transmission. In south-central Spain, overabundant wild boar are reservoirs of Mycobacterium bovis, and related members of the Mycobacterium tuberculosis complex (MTBC), the causative agents of bovine tuberculosis (bTB). An indirect enzyme-linked immunosorbent assay using bovine-purified protein derivative was applied to determine the spatial and temporal distribution of wild boar contact with MTBC in the Iberian Peninsula and to model and identify the associated risk factors. Wild boar apparent seroprevalence was 22%. Seropositives were detected in 71% of 81 sites, including 23 sites where wildlife was thought to be bTB free. The results described a new geographic range of wild boar contact with MTBC and a stable prevalence in this wildlife reservoir that contrasts with the success of bTB control in cattle. Inference of which host (wild boar or cattle) is driving bTB maintenance was not ...
A rising isolation trend of drug-resistant M. bovis from human clinical cases is documented in the literature. Here we assessed Mycobacterium tuberculosis complex isolates from cattle for drug susceptibility by the gold standard agar proportion method and a simplified resazurin microtitre assay (d-REMA). A total of 38 M. tuberculosis complex strains, including M. bovis (n = 36) and M. caprae (n = 2) isolates, from cattle in Tunisia were tested against isoniazid, rifampin, streptomycin, ethambutol, kanamycin and pyrazinamide. M. caprae isolates were found to be susceptible to all test drugs. All M. bovis strains were resistant to pyrazinamide, as expected. In addition, one M. bovis isolate showed high-level resistance to streptomycin (MIC | 500.0 μg/ml). Concordant results with the two methods were found. The most common target genes associated with streptomycin resistance, namely the rrs, rpsL and gidB genes, were DNA sequenced. A non-synonymous mutation at codon 43 (K43R) was found in the rpsL gene.
Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the central regulator of peroxide stress response in enteric bacteria. Inactivation of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis complex. This phenomenon appears as a paradox due to the ability of this organism to parasitize host macrophages, in which the ingested organisms are likely to be exposed to reactive oxygen intermediates. However, the surprising finding that M. tuberculosis has multiple deletions, nonsense and frameshift mutations in oxyR may help explain the exceptionally high sensitivity of M. tuberculosis to the potent antituberculosis agent isoniazid. One of the genes affected by oxyR lesions, ahpC (encoding an alkylhydroperoxide reductase) may determine the intrinsic sensitivity of mycobacteria to isoniazid.
Background and objectives: Tuberculosis (TB) is the major public health problem in the world. Each year there are 2-3 million deaths worldwide caused by TB. The increasing incidence of Multi Drug Resistance tuberculosis (MDR-TB) worldwide highlights the urgent need to search for new anti-tuberculosis compounds. It has been reported that medicinal plant, Dracocephalum kotschyi, possesses some antibacterial effect, thus in the present study its anti-mycobacterial property was evaluated. Methods: The sensitivity and resistance of M. tuberculosis strains at concentration of 0.2 µg/mL isoniazid was determined by proportion method. Methanol extract of D. kotschyi was prepared using maceration method. Six concentrations of D. kotschyi, including 20, 40, 80, 160, 320 and 640μg/mL were prepared and its anti-mycobacterial effect on four groups of M. tuberculosis including M. tuberculosis H37Rv (ATCC 27294), isoniazid susceptible and resistance and MDR strains was determined. Results: The methanol extract of D.
TY - JOUR. T1 - Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. AU - Lee, Hyo Ji. AU - Ko, Hyun Jeong. AU - Kim, Seung Hyun. AU - Jung, Yu Jin. PY - 2019/3. Y1 - 2019/3. N2 - Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing the autophagy via the ...
Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the ...
The Mycobacterium tuberculosis exported repetitive protein (RvErp) is a crucial virulence-associated factor as determined by its role in the survival and multiplication of mycobacteria in cultured macrophages and in vivo Although attempts have been made to understand the function of Erp protein, its exact role in Mycobacterium pathogenesis is still elusive. One way to determine this is by searching for novel interactions of RvErp. Using a yeast two-hybrid assay, an adenylyl cyclase (AC), Rv2212, was found to interact with RvErp. The interaction between RvErp and Rv2212 is direct and occurs at the endogenous level. The Erp protein of Mycobacterium smegmatis (MSMEG_6405, or MsErp) interacts neither with Rv2212 nor with Ms_4279, the M. smegmatis homologue of Rv2212. Deletion mutants of Rv2212 revealed its adenylyl cyclase domain to be responsible for the interaction. RvErp enhances Rv2212-mediated cyclic AMP (cAMP) production. Also, the biological significance of the interaction between RvErp and ...
An evaluation of the utility of rep PCR typing compared to the 15 loci discriminatory set of MIRU-VNTR was undertaken. Twenty-nine isolates of Mycobacterium tuberculosis from patients were examined. Genomic DNA was extracted from the isolates by standard method. The number of copies of tandem repeats of the 15 MIRU-VNTR loci was determined by PCR amplification and agarose gel electrophoresis of the amplicons. M. tuberculosis outbreak-related strains were distinguished from other isolates. MIRU-VNTR typing identified 4 major clusters of strains. The same isolates clustered together after RFLP typing, but rep-PCR identified only 3 of them. The concordance between RFLP and MIRU-VNTR typing was complete, with the exception of two isolates with identical RFLP patterns that differed in the number of tandem repeat copies at two MIRU-VNTR alleles. A further isolate, even sharing the same RFLP pattern, differed by one repeat from the rest of its cluster. We also tested the use of an automated rep-PCR for ...
Even though LTBI is estimated to affect more than a billion people, latency of this disease is only partially understood. We use clinical samples to characterize the immune response in patients diagnosed with LTBI. Our studies, performed in collaboration with scientists at Addis Ababa University focus on human cohorts living in proximity to livestock. In this context, we are interested in M. tuberculosis and M. bovis transmission between livestock to human. We investigate the effects of the respiratory tract microbiome and strain lineages on TB outcome using genomic methods.. ...
Home » Type i IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-γ ...
Results 178 cases and 57 cases were included in 2G group and 3G group, respectively. Mean age in 2G group and 3G group were 59.3 years old and 60.4 years old, respectively. 5 cases in 2G group have past history of TB infection and none in 3G group. 5 cases in 2G group (2.8%) and 6 cases in 3G group (10.5%) have positive results and there was a significant difference (p=0.027). 157 cases in 2G group (88.2%) and 42 cases in 3G group (73.7%) have negative results and there was a significant difference (p=0.011). In 10 cases that had positive results of QFT 2G or 3G, none had past history of TB, chest CT was normal in 4 cases and chemoprophylaxis of isoniazid (INH) was performed in 5 cases. Although biologics was used in 7 cases among 10 QFT-positive cases, no active TB was occurred until last observation. Used biologics were infliximab in 2 cases, etanercept in a case, abatacept in 3 cases and golimumab in a case.. ...
A hallmark of M. tuberculosis is its ability to infect, survive in, and persist in human macrophages. Acquired immunity, mediated primarily by MHC-II-restricted IFN-γ-producing CD4+ T cells, controls M. tuberculosis infection but fails to eradicate the organism. When acquired immunity fails because of aging, malnutrition, or human immunodeficiency virus type 1 infection, persistent macrophage-bound M. tuberculosis bacilli emerge to cause reactivation tuberculosis. The mechanism(s) used by M. tuberculosis to persist for many years in macrophages in the face of highly developed and active acquired T-cell responses, reflected in strongly positive tuberculin skin test reactivity, is poorly understood. Earlier studies established that M. tuberculosis can interfere with IFN-γ-mediated activation and IFN-γR signaling in human macrophages (41). However, the molecules of M. tuberculosis that are responsible for interference with IFN-γ signaling have not been characterized.. In earlier studies, we ...
The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC90 value of 1.5 μM.
Folate biosynthesis is an established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced into clinical practice based on target-based drug discovery. Fifty years later, PAS continues in use for tuberculosis. PAS is assumed to inhibit dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis (M. tuberculosis) by mimicking the substrate, p-aminobenzoate (PABA). However, we found that sulfonamide inhibitors of DHPS inhibited growth of M. tuberculosis only weakly due to their intracellular metabolism. PAS, by contrast, served as a replacement substrate for DHPS. Products of PAS metabolism at this and subsequent steps in folate metabolism inhibited those enzymes, competing with their substrates. PAS is thus a prodrug that blocks growth of M. tuberculosis when its active forms are generated by enzymes in the pathway they poison.. ...
Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes. ...
Fosmidomycin is a phosphonic antibiotic which inhibits 1-deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr), the first committed step of the non-mevalonate pathway of isoprenoid biosynthesis. In Mycobacterium tuberculosis Dxr is encoded by Rv2870c, and although the antibiotic has been shown to inhibit the recombinant enzyme [1], mycobacteria are intrinsically resistant to fosmidomycin at the whole cell level. Fosmidomycin is a hydrophilic molecule and in many bacteria its uptake is an active process involving a cAMP dependent glycerol-3-phosphate transporter (GlpT). The fact that there is no glpT homologue in the M. tuberculosis genome and the highly impervious nature of the hydrophobic mycobacterial cell wall suggests that resistance may be due to a lack of cellular penetration. We demonstrated that dxr (Rv2780c) is an essential gene in M. tuberculosis, since we could not delete the chromosomal copy unless a second functional copy was provided on an integrating vector. This confirmed that the
IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) causes the disease tuberculosis (TB), which kills more people than any other infection. The emergence of drug-resistant Mtb strains has exacerbated this already alarming epidemic. The authors have identified a small molecule, C10, that potentiates the activity of the frontline antibiotic isoniazid (INH) and prevents the selection for INH-resistant mutants. They find that C10 can even reverse INH resistance in Mtb. Therefore, our study reveals vulnerabilities that can be exploited to reverse INH resistance in Mtb.. ...
The genome of Mycobacterium tuberculosis H37Rv includes a homologue of the CRP/FNR (cAMP receptor protein/fumarate and nitrate reduction regulator) family of transcription regulators encoded by Rv3676. Sequencing of the orthologous gene from attenuated Mycobacterium bovis Bacille Calmette-Guérin (BCG) strains revealed point mutations that affect the putative DNA-binding and cNMP-binding domains of the encoded protein. These mutations are not present in the published sequences of the Rv3676 orthologues in M. bovis, M. tuberculosis or Mycobacterium leprae. An Escherichia coli lacZ reporter system was used to show that the M. tuberculosis Rv3676 protein binds to DNA sites for CRP, but this DNA binding was decreased or abolished with the Rv3676 protein counterparts from BCG strains. The DNA-binding ability of the M. tuberculosis Rv3676 protein was decreased by the introduction of base changes corresponding to the BCG point mutations. Conversely, the DNA binding of the BCG Rv3676 proteins from BCG strains
Drumm JE, Mi K, Bilder P, Sun M, Lim J, Bielefeldt-Ohmann H, Basaraba R, So M, Zhu G, Tufariello JM, Izzo AA, Orme IM, Almo SC, Leyh TS, Chan J. 2009. Mycobacterium tuberculosis universal stress protein Rv2623 regulates bacillary growth by ATP-Binding: requirement for establishing chronic persistent infection. PLoS Pathog 5:e1000460. Russell-Goldman E, Xu J, Wang X, Chan J, Tufariello JM. 2008. A double Rpf knockout Mycobacterium tuberculosis strain exhibits profound defects in reactivation from chronic tuberculosis and innate immunity phenotypes. Infect Immun. 76:4269-81.. Maglione PJ, Xu J, Casadevall A, Chan J. 2008. Fcgamma receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis Infection. J Immunol 180:3329-38.. Chakravarty SD, Zhu G, Tsai MC, Mohan VP, Marino S, Kirschner DE, Huang L, Flynn J, Chan J. 2008. Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. Infect ...
A ∼500-member library of bidentate inhibitors against protein tyrosine phosphatases (PTPs) was rapidly assembled using click chemistry. Subsequent high-throughput screening had led to the discovery of highly potent (K i as low as 150 nM) and selective MptpB inhibitors, some of which represent the most potent MptpB inhibitors developed to date. © 2009 American Chemical society ...
The family of mycobacteria is composed of pathogenic and apathogenic bacteria. This study was performed with 3 members of this family, the most prominent pathogenic member, Mycobacterium tuberculosis, the causative agent of tuberculosis, the vaccine strain Mycobacterium bovis BCG which was developed by attenuation of the bovine tuberculosis agent Mycobacterium bovis, and Mycobacterium smegmatis which is apathogenic and widely distributed in soil. A key to understanding mycobacteria and, especially, their resistance is to understand the complexity of their cell wall. Peptidoglycan is a major component of the cell wall and the transport of peptidoglycan precursors out of the cytoplasm to the bacterial surface by undecaprenyl monophosphate is central to cell wall synthesis. Therefore, deletion mutants of the undecaprenyl phosphokinase gene (upk) were generated in M. tuberculosis, M. bovis BCG, and M. smegmatis. In the case of M. smegmatis it was shown that a delta upk deletion mutant, as with ...
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