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mycobacterium tuberculosis 10-kda co-chaperonin regulates the expression levels of receptor activator of nuclear factor-κb ligand and osteoprotegerin in human osteoblasts.the aim of the present study was to investigate the effect of recombinant mycobacterium tuberculosis (r-mt) 10-kda co-chaperonin (cpn10) on the expression of osteoprotegerin (opg) and receptor activator of nuclear factor-κb ligand (rankl) in third-generation cultured osteoblasts. the osteoblast-like cultures were isolated from bone fragments taken from patients undergoing surgery. prior to stimulation with r-mt cpn10, cells were incubated in serum-free medium for 24 h. r-mt cpn10 was added into ...201525667654
filarial infection modulates the immune response to mycobacterium tuberculosis through expansion of cd4+ il-4 memory t cells.exaggerated cd4(+) t helper 2-specific cytokine producing memory t cell responses developing concomitantly with a t helper 1 response might have a detrimental role in immunity to infection caused by mycobacterium tuberculosis. to assess the dynamics of ag-specific memory t cell compartments in the context of filarial infection, we used multiparameter flow cytometry on pbmcs from 25 microfilaremic filarial-infected (inf) and 14 filarial-uninfected (uninf) subjects following stimulation with filar ...201525667413
inhibition of m. tuberculosis β-ketoacyl coa reductase fabg4 (rv0242c) by triazole linked polyphenol-aminobenzene hybrids: comparison with the corresponding gallate counterparts.herein we report six novel triazole linked polyphenol-aminobenzene hybrids (3-8) as inhibitors of mycobacterium tuberculosis fabg4 (rv0242c), a less explored β-ketoacyl coa reductase that has immense potential to be the future anti-tuberculosis drug target due to its possible involvement in drug resistance and latent infection. novel triazole linked polyphenol-aminobenzene hybrids have been synthesized, characterized and evaluated for their inhibitory activity against fabg4. all of them inhibit ...201525666821
exit from mycobacterial dormancy: a structural perspective.dormancy in mycobacteria is defined as a stable but reversible non-replicating state in response to stresses. in mycobacterium tuberculosis, an important human pathogen, this state is responsible for latent tuberculosis. the current chemotherapy to defeat tuberculosis while effective in killing growing tubercle bacilli is largely ineffective in killing dormant bacilli. for this reason there is a recent interest to develop new drugs against this disease in the latent form. to this aim, the knowle ...201525666798
proteome analysis of ofloxacin and moxifloxacin induced mycobacterium tuberculosis isolates by proteomic approach.ofloxacin (ofx) and moxifloxacin (mox) are the most promising second line drugs for tuberculosis treatment. although the primary mechanism of action of ofx and mox is gyrase inhibition, other possible mechanisms cannot be ruled out. being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics. in this study we have investigated the proteomic changes of mycobacterium tuberculosis isolates induced by ofx and mox by applying comparative ...201525666036
evidence that phosphorylation of threonine in the gt motif triggers activation of pkna, a eukaryotic-type serine/threonine kinase from mycobacterium tuberculosis.phosphorylation of the activation loop in the catalytic domain of the rd family of bacterial eukaryotic-type ser/thr protein kinases (stpk) induces their conformational transition from an inactive to active state. however, mechanistic insights into the phosphorylation-mediated transition of these stpks from an inactive to active state remain unknown. in the present study, we addressed this issue with pkna, an essential stpk from mycobacterium tuberculosis. we found that the catalytic activity of ...201525665034
unusual presentation of tuberculosis in an elderly male: a case report.tuberculous liver abscess is an extremely rare condition, even in tuberculosis endemic countries. a 68-year-old male presented with 2 months of fever, significant weight loss, and hepatomegaly. ultrasonography revealed a right hepatic lobe abscess. guided aspiration of the fluid showed tubercular bacilli. he had no evidence of active tuberculosis elsewhere.201525678973
profile of delamanid for the treatment of multidrug-resistant tuberculosis.new approaches to the treatment of multidrug-resistant and extensively drug-resistant tuberculosis (tb) are badly needed. not only is the success rate of current treatment regimens suboptimal but existing regimens require multiple drugs and lengthy courses and may lead to significant toxicities. the treatment landscape is beginning to shift, however, with the recent approvals of the new tb drugs bedaquiline and delamanid. delamanid, a dihydro-imidazooxazole, has been shown to have excellent acti ...201525678771
correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel mycobacterium tuberculosis fusion protein: a multivariate analysis study.in this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis.201525677402
outbreak of extrapulmonary tuberculosis infection associated with acupuncture point injection.mycobacterium tuberculosis infection is rarely reported to be associated with acupuncture practices. we performed a retrospective outbreak investigation of a unique outbreak of 33 extrapulmonary m. tuberculosis infections related to acupuncture point injection therapy (ait) among clients who visited a private traditional chinese medicine clinical centre in china. the lumps, abscesses and ulcers occurred mostly on the neck, shoulders, waist, knees and hips, localized at acupuncture point meridian ...201525677256
synthesis and antimicrobial evaluation of 6-alkylamino-n-phenylpyrazine-2-carboxamides.this work presents synthesis and antimicrobial evaluation of nineteen 6-alkylamino-n-phenylpyrazine-2-carboxamides. antimycobacterial activity was determined against mycobacterium tuberculosis h37rv, m. kansasii and two strains of m. avium. generally, the antimycobacterial activity increased with prolongation of simple alkyl chain and culminated in compounds with heptylamino substitution (3e, 4e) with mic = 5-10 μm against m. tuberculosis h37rv. on the contrary, derivatives with modified alkyl c ...201525676890
the extracellular matrix regulates granuloma necrosis in tuberculosis.a central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. we reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. in human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. in mice, transgenic expression of human matrix met ...201525676469
novel inhibitors of cholesterol degradation in mycobacterium tuberculosis reveal how the bacterium's metabolism is constrained by the intracellular environment.mycobacterium tuberculosis (mtb) relies on a specialized set of metabolic pathways to support growth in macrophages. by conducting an extensive, unbiased chemical screen to identify small molecules that inhibit mtb metabolism within macrophages, we identified a significant number of novel compounds that limit mtb growth in macrophages and in medium containing cholesterol as the principle carbon source. based on this observation, we developed a chemical-rescue strategy to identify compounds that ...201525675247
clinical utility of anti-lipoarabinomannan antibodies testing for the diagnosis of tuberculous arthritis.diagnosis of extrapulmonary tuberculosis (tb) is often challenging. in this work we discuss the utility of an assay for lipoarabinomannan (lam) antibody detection in synovial fluid. lam is one of the three major groups of lipopolysaccharides within the mycobacterium tuberculosis (mtb) cell wall. an elisa based test was used to investigate the presence of antibodies against lam in an immunocompetent patient with knee arthritis. the symptoms resolved after isoniazid treatment. lam positivity has b ...201525674511
structure of espb from the esx-1 type vii secretion system and insights into its export mechanism.mycobacterium tuberculosis (mtb) uses the esx-1 type vii secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal membrane, facilitating the escape and cell-to-cell spread of mtb. esx-1 membranolytic activity depends on a set of specialized secreted esp proteins, the structure and specific roles of which are not currently understood. here, we report the x-ray and electron microscopic structures of the esx-1-secreted ...201525684576
an overview of tuberculosis plant-derived vaccines.tuberculosis (tb) is a leading fatal infectious disease to which the current bcg vaccine has a questionable efficacy in adults. thus, the development of improved vaccines against tb is needed. in addition, decreasing the cost of vaccine formulations is required for broader vaccination coverage through global vaccination programs. in this regard, the use of plants as biofactories and delivery vehicles of tb vaccines has been researched over the last decade. these studies are systematically analyz ...201525683476
microrna let-7 modulates the immune response to mycobacterium tuberculosis infection via control of a20, an inhibitor of the nf-κb pathway.the outcome of the interaction between mycobacterium tuberculosis (mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. micrornas critically regulate several host defense mechanisms, but their role in the mtb-macrophage interplay remains unclear. microrna profiling of mtb-infected macrophages revealed the downregulation of mir-let-7f in a manner dependent on the mtb secreted effector esat-6. we establish that let-7f targets a20, a feedba ...201525683052
[cutaneous tuberculosis and erythema induratum: a retrospective study of 13 cases in france].tuberculosis is the most common mycobacterial disease in the world. the cutaneous form is rare in low endemic countries. the occurrence of several cutaneous tuberculosis cases in our dermatology department during 2011-2012 led us to investigate whether there was a resurgence of cutaneous tuberculosis in france. the aim was to analyse changes in cutaneous tuberculosis and the related clinical, microbiological and therapeutic data.201525683015
recent advances in the chemistry and biology of benzothiazoles.benzothiazole is a privileged heterocyclic scaffold having a benzene ring fused with a five-membered thiazole ring. this moiety has attracted considerable attention because of its wide range of pharmacological activities such as antitubercular, antimicrobial, antimalarial, anticonvulsant, anthelmintic, analgesic, anti-inflammatory, antidiabetic, antitumor activity, etc. in the last few years, some novel benzothiazoles have been developed with varied biological activities. to access this scaffold ...201525682746
identification of mycobacterium tuberculosis ppe68-specific hla-a*0201-restricted epitopes for tuberculosis diagnosis.ppe68 is a mycobacterium tuberculosis-specific protein which is absent from the vaccine strains of bcg. a panel of 14 ppe68-derived peptides predicted to bind to hla-a*0201 was synthesized. the hla-a*0201 restriction of these peptides was determined in t2 cell line and hla-a*0201 transgenic mice. the specificity of peptides was assessed in pulmonary tuberculosis (tb) patients using ifn-γ enzyme-linked immunospot (elispot) assay, and immunodominant peptides were further used to evaluate their dia ...201525682073
combined molecular dynamics, std-nmr, and corcema protocol yields structural model for a udp-galactopyranose mutase-inhibitor complex.udp-galactopyranose mutase (ugm) is an enzyme involved in the biosynthesis of the mycobacterium tuberculosis cell wall, and is essential for the growth and survival of the organism. a micromolar inhibitor developed by tetrafluorination of the ugm substrate has been previously studied by saturation transfer difference (std) nmr spectroscopy. to elucidate the bioactive conformation of the inhibitor bound to ugm, we employ molecular dynamics (md) simulations to construct a structural model. the md ...201525681227
modified calanolides incorporated with furan-2-nitro mimics against mycobacterium tuberculosis.(+)-calanolide a was identified as an active agent against both hiv-1 and mycobacterium tuberculosis (mtb). we modified ring d of calanolide compounds with furan-2-nitro mimics and obtained 15 compounds. after in vitro tests, two compounds were shown to be active against replicating (r) mtb, but not against non-replicating (nr) mtb. further optimization for potent candidates against both r mtb and nr mtb will result from this research.201525681226
natural antimicrobial peptides against mycobacterium tuberculosis.tb, caused by mycobacterium tuberculosis, is one the leading infectious diseases worldwide. there is an urgent need to discover new drugs with unique structures and uncommon mechanisms of action to treat m. tuberculosis and combat antimycobacterial resistance. naturally occurring compounds contain a wide diversity of chemical structures, displaying a wide range of in vitro potency towards m. tuberculosis. a number of recent studies have shown that natural antimycobacterial peptides can disrupt t ...201525681127
latent tuberculosis infection in rural china: baseline results of a population-based, multicentre, prospective cohort study.prophylactic treatment of individuals with latent mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. in china, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. we aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in china.201525681063
differential expression of efflux pump genes of mycobacterium tuberculosis in response to varied subinhibitory concentrations of antituberculosis agents.several reports have elaborated on the role of efflux pumps in drug resistance in mycobacterium tuberculosis by analysing the mrna expression profiles. however, there is no uniformity in the subinhibitory concentrations of drugs chosen in these studies. some investigators studied the expression of efflux pumps under a drug concentration of 1/2 minimum inhibitory concentration (mic), while others used 1/3, 1/4 or 1/8mic. the present study was planned to understand the effect of different concentr ...201525680943
direct identification of mycobacteria from clinical specimens by multiplex real-time pcr.to directly identify clinically relevant mycobacteria from clinical specimens, we have developed a multiplex real-time pcr assay with hydrolysis probes that can identify 20 mycobacterial species.201525715744
integrated microfluidic card with taqman probes and high-resolution melt analysis to detect tuberculosis drug resistance mutations across 10 genes.genotypic methods for drug susceptibility testing of mycobacterium tuberculosis are desirable to speed the diagnosis and proper therapy of tuberculosis (tb). however, the numbers of genes and polymorphisms implicated in resistance have proliferated, challenging diagnostic design. we developed a microfluidic taqman array card (tac) that utilizes both sequence-specific probes and high-resolution melt analysis (hrm), providing two layers of detection of mutations. twenty-seven primer pairs and 40 p ...201525714709
protein kinase a (pkna) of mycobacterium tuberculosis is independently activated and is critical for growth in vitro and survival of the pathogen in the host.the essential mycobacterial protein kinases pkna and pknb play crucial roles in modulating cell shape and division. however, the precise in vivo functional aspects of pkna have not been investigated. this study aims to dissect the role of pkna in mediating cell survival in vitro as well as in vivo. we observed aberrant cell shape and severe growth defects when pkna was depleted. using the mouse infection model, we observe that pkna is essential for survival of the pathogen in the host. complemen ...201525713147
gene silencing by crispr interference in mycobacteria.recombination-based tools for introducing targeted genomic mutations in mycobacterium tuberculosis are not efficient due to higher rate of illegitimate recombination compared with homologous dna exchange. moreover, involvement of multiple steps and specialized reagents make these tools cost ineffective. here we introduce a novel clustered regularly interspaced short palindromic repeat (crispr) interference (crispri) approach that efficiently represses expression of target genes in mycobacteria. ...201525711368
design, synthesis and evaluation of fe-s targeted adenosine 5'-phosphosulfate reductase inhibitors.adenosine 5'-phosphosulfate reductase (apr) is an iron-sulfur enzyme that is vital for survival of mycobacterium tuberculosis during dormancy and is an attractive target for the treatment of latent tuberculosis (tb) infection. the 4fe-4s cluster is coordinated to apr by sulfur atoms of four cysteine residues, is proximal to substrate, adenosine 5'-phopsphosulfate (aps), and is essential for catalytic activity. herein, we present an approach for the development of a new class of apr inhibitors. a ...201525710356
mycobacterium tuberculosis effectors involved in host-pathogen interaction revealed by a multiple scales integrative pipeline.mycobacterium tuberculosis (mtb) has evolved multiple strategies to counter host immunity. proteins are one important player in the host-pathogen interaction. a comprehensive list of such proteins will benefit our understanding of pathogenesis of mtb.201525709069
role of the horizontal gene exchange in evolution of pathogenic mycobacteria.mycobacterium tuberculosis is one of the most dangerous human pathogens, the causative agent of tuberculosis. while this pathogen is considered as extremely clonal and resistant to horizontal gene exchange, there are many facts supporting the hypothesis that on the early stages of evolution the development of pathogenicity of ancestral mtb has started with a horizontal acquisition of virulence factors. episodes of infections caused by non-tuberculosis mycobacteria reported worldwide may suggest ...201525708825
management of emerging multidrug-resistant tuberculosis in a low-prevalence setting.multidrug-resistant (mdr) tuberculosis (tb) is an emerging concern in communities with a low tb prevalence and a high standard of public health. twenty-three consecutive adult mdr tb patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-tb treatment management, which included surgical procedures and long-term patient follow-up. this report of our experience emphasizes the need for an individualized approach as mdr tb brings myco ...201525708551
mechanistic analysis elucidating the relationship between lys96 mutation in mycobacterium tuberculosis pyrazinamidase enzyme and pyrazinamide susceptibility. 201525708048
[evaluation of second-line antituberculosis drug susceptibilities of multidrug-resistant mycobacterium tuberculosis complex isolates by e-test method].multidrug-resistant (mdr) tuberculosis (tb) constitutes a restricting factor for the effective treatment of tb worldwide. early diagnosis and appropriate treatment of patients are the most effective strategy in the control of mdr-tb. therefore, knowledge of drug resistance patterns of the mdr-tb clinical isolates are necessary in planning of an appropriate treatment regimen for the patient. the aims of this study were to detect the susceptibilities of mdr-tb isolates to second-line anti-tb drugs ...201525706730
latent tuberculosis infection among a large cohort of medical students at a teaching hospital in italy.the surveillance of latent tuberculosis infection (ltbi) in both healthcare workers and healthcare students is considered fundamental for tuberculosis (tb) prevention. the aim of the present study was to estimate ltbi prevalence and evaluate potential risk-factors associated with this condition in a large cohort of medical students in italy. in a cross-sectional study, performed between march and december 2012, 1511 eligible subjects attending the medical school of the university of genoa, train ...201525705685
the dosr regulon modulates adaptive immunity and is essential for mycobacterium tuberculosis persistence.hypoxia promotes dormancy by causing physiologic changes to actively replicating mycobacterium tuberculosis. dosr controls the response of m. tuberculosis to hypoxia.201525730547
a bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis.detection of cyclic-di-adenosine monophosphate (c-di-amp), a bacterial second messenger, by the host cytoplasmic surveillance pathway (csp) is known to elicit type i interferon (ifn) responses, which are crucial to antimicrobial defense. however, the mechanisms and role of c-di-amp signaling in mycobacterium tuberculosis virulence remain unclear. here we show that resistance to tuberculosis requires csp-mediated detection of c-di-amp produced by m. tuberculosis and that levels of c-di-amp modula ...201525730264
tuberculosis of the neuromusculoskeletal system: a review of two cases presenting as chiropractic patients.tuberculosis caused by mycobacterium tuberculosis is a major public heath problem world-wide, particularly in low-income countries. increased number of immunocompromised patients and immigration from countries where tuberculosis is endemic has resulted in increased number of cases in high-income countries. tuberculosis can affect any organ system, but is of particular interest to chiropractors when it affects the neuromusculoskeletal system. patients with tuberculosis of the neuromusculoskeletal ...201525729081
proteasomal control of cytokinin synthesis protects mycobacterium tuberculosis against nitric oxide.one of several roles of the mycobacterium tuberculosis proteasome is to defend against host-produced nitric oxide (no), a free radical that can damage numerous biological macromolecules. mutations that inactivate proteasomal degradation in mycobacterium tuberculosis result in bacteria that are hypersensitive to no and attenuated for growth in vivo, but it was not known why. to elucidate the link between proteasome function, no resistance, and pathogenesis, we screened for suppressors of no hyper ...201525728768
antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against mycobacterium tuberculosis in a series of in vitro and in vivo models.new pyridopyrimidine derivatives were defined using a novel hts in silico docking method (frigate). the target protein was a dutpase enzyme (ec 3.6.1.23; rv2697) which plays a key role in nucleotide biosynthesis of mycobacterium tuberculosis (mtb). top hit molecules were assayed in vitro for their antimycobacterial effect on mtb h37rv culture. in order to enhance the cellular uptake rate, the tb820 compound was conjugated to a peptid-based carrier and a nanoparticle type delivery system (polylac ...201525728610
regulatory t-cell subsets in response to specific mycobacterium tuberculosis antigens in vitro distinguish among individuals with different qtf and tst reactivity.regulatory t cells (tregs), a subset of cd4+ t cells related with immune regulation, have been associated with active and latent tuberculosis infection (ltbi). treg frequencies were evaluated by multicolor flow cytometry (fc) in peripheral blood mononuclear cells (pbmcs) stimulated with mycobacterial antigens esat-6, cfp-10, and tb7.7 to assess their capacity to distinguish subjects with different reactivity to the quantiferon-tb® gold in-tube (qft-it) test and the tuberculin skin test (tst). in ...201525728490
development of sample clean up methods for the analysis of mycobacterium tuberculosis methyl mycocerosate biomarkers in sputum extracts by gas chromatography-mass spectrometry.a proof of principle gas chromatography-mass spectrometry method is presented, in combination with clean up assays, aiming to improve the analysis of methyl mycocerosate tuberculosis biomarkers from sputum. methyl mycocerosates are generated from the transesterification of phthiocerol dimycocerosates (pdims), extracted in petroleum ether from sputum of tuberculosis suspect patients. when a high matrix background is present in the sputum extracts, the identification of the chromatographic peaks c ...201525728371
direct detection of mycobacterium tuberculosis in sputum using combined solid phase extraction-gas chromatography-mass spectrometry.recently, thermally-assisted hydrolysis and methylation followed by gas chromatography-mass spectrometry (thm-gc-ms) in combination with chemometrics has been used to develop a 20-compound model for fast differentiation of mycobacterium tuberculosis (mtb) from non-tuberculous mycobacteria (ntm) in bacterial cultures. this model provided better than 95% accuracy. in our current work a hexane/methanol/water extraction followed by a solid phase extraction (spe) clean-up procedure was developed for ...201525728368
congenital tuberculosis: presentation of a rare case.congenital tuberculosis is a rare disease with a high mortality rate. congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. the case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory di ...201525727833
detection of mycobacterium tuberculosis dna on the oral mucosa of tuberculosis patients.diagnosis of pulmonary tuberculosis (tb) usually includes laboratory analysis of sputum, a viscous material derived from deep in the airways of patients with active disease. as a diagnostic sample matrix, sputum can be difficult to collect and analyze by microbiological and molecular techniques. an alternative, less invasive sample matrix could greatly simplify tb diagnosis. we hypothesized that mycobacterium tuberculosis cells or dna accumulate on the oral epithelia of pulmonary tb patients, an ...201525727773
phylogeny to function: pe/ppe protein evolution and impact on mycobacterium tuberculosis pathogenicity.the pe/ppe genes represent one of the most intriguing aspects of the mycobacterium tuberculosis genome. these genes are especially abundant in pathogenic mycobacteria, with more than 160 members in m. tuberculosis. despite being discovered over 15 years ago, their function remains unclear, although various lines of evidence implicate selected family members in mycobacterial virulence. in this review, we use pe/ppe phylogeny as a framework within which we examine the diversity and putative functi ...201525727695
3d-qsar and molecular modeling studies on 2,3-dideoxy hexenopyranosid-4-uloses as anti-tubercular agents targeting alpha-mannosidase.ligand-based and structure-based methods were applied in combination to exploit the physicochemical properties of 2,3-dideoxy hex-2-enopyranosid-4-uloses against mycobacterium tuberculosis h37rv. statistically valid 3d-qsar models with good correlation and predictive power were obtained with comfa steric and electrostatic fields (r(2) = 0.797, q(2) = 0.589) and comsia with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2) = 0.867, q(2) = 0.570) based on training ...201525727263
decompression of enlarged mediastinal lymph nodes due to mycobacterium tuberculosis causing severe airway obstruction in children.large airway compression by enlarged tuberculosis (tb) lymph nodes results in life-threatening airway obstruction in a small proportion of children. the indications, safety, and efficacy of tb lymph node decompression are inadequately described. this study aims to describe the indications and efficacy of tb lymph node decompression in children with severe airway compression and investigate variables influencing outcome.201525725929
genital tuberculosis in the infertile women - an update.tuberculosis is endemic in many developing countries of the world including bangladesh. genital tuberculosis is a significant cause of infertility in the women of these countries. the diagnosis of genital tuberculosis in infertile women is difficult as most of the cases are usually asymptomatic. a high index of clinical suspicion is required. genital tuberculosis always affects the fallopian tubes. it affects the endometrium in half of the cases. in addition to tuberculin skin tests and interfer ...201525725695
anti-mycobacterial triterpenes from the canadian medicinal plant alnus incana.alnus incana, commonly known as the gray or speckled alder, is a medicinal plant used by some canadian first nations to treat symptoms associated with tuberculosis. the aim of this study was to assess the anti-mycobacterial activity of an alnus incana bark extract and to identify the active constituents of the extract.201525725435
definite (microbiologically confirmed) tuberculous meningitis: predictors and prognostic impact.microbiological confirmation cannot be obtained in approximately two-third patients with tuberculous meningitis. in this study, we sought to identify epidemiological, clinical, cerebrospinal fluid, and imaging parameters that could indicate the possibility of microbiological confirmation among patients with suspected tuberculous meningitis.201525724799
detection of novel and reported mutations in the rpob, katg and inha genes in multidrug-resistant tuberculosis isolates: a hospital-based study.the objective of this study was to detect mutations associated with isoniazid (inh) and rifampicin (rif) resistance in mycobacterium tuberculosis isolates from newly diagnosed and previously treated tuberculosis patients using a pcr-based dna sequencing technique. phenotypic drug susceptibility testing was performed using a bactec™ micromgit culture system in 354 m. tuberculosis isolates. among the 354 isolates, 18 were multidrug-resistant tuberculosis (mdr-tb). pcr-based dna sequencing was perf ...201527873643
tuberculous bursitis of the greater trochanter mimicking ankylosing spondylitis.tuberculous trochanteric bursitis (ttb) is a rare condition that accounts for 1% of musculoskeletal tuberculosis cases. extrapulmonary tb is usually diagnosed late because of reduced diagnostic suspicion, particularly in the absence of signs of systemic infection. herein, we report a case of right hip pain that was misdiagnosed as ankylosing spondylitis. the patient had a history of inflammatory back pain with morning stiffness. however, hla-b27 was negative. sacroiliac magnetic resonance imagin ...201527708917
prognostic significance of novel katg mutations in mycobacterium tuberculosis.by using whole genome sequencing (wgs), researchers are beginning to understand the genetic diversity of mycobacterium tuberculosis (mtb) and its consequences for the diagnosis of multidrug-resistant tuberculosis (mdr-tb) on a genomic scale. the global consortium for drug-resistant tb diagnostics (gcdd) conducted a genome scale variant analyses of 366 clinical mtb genomes (mostly mdr/xdr [extensively drug resistant]) from four countries in order to inform the development of rapid molecular diagn ...201527695670
molecular model of hemoglobin n from mycobacterium tuberculosis bound to lipid bilayers: a combined spectroscopic and computational study.a singular aspect of the 2-on-2 hemoglobin structures of groups i and ii is the presence of tunnels linking the protein surface to the distal heme pocket, supporting the storage and the diffusion of small apolar ligands to/from the buried active site. as the solubility of apolar ligands is greater in biological membranes than in solution, the association of these proteins with biological membranes may improve the efficiency of ligand capture. as very little is known on this subject, we have inve ...201525723781
early detection of multi-drug resistance and common mutations in mycobacterium tuberculosis isolates from delhi using genotype mtbdrplus assay.there is scarcity of prevalence data of multi-drug-resistant tuberculosis (mdr-tb) data and common mutations responsible in north india. this study aimed to detect mdr-tb among mdr-tb suspects from delhi and mutation patterns using genotype mtbdrplus assay.201525657156
association of mycobacterium tuberculosis in the causation of eales' disease: an institutional experience.eales' disease is an idiopathic retinal vasculitis characterized by retinal inflammation, ischemia, and neo-vascularisation. it frequently causes massive vitreous haemorrhage and retinal detachment leading to blindness. although the exact etiology is unknown, this condition is considered to be a consequence of hypersensitivity reaction to tubercular protein due to previous mycobacterium tuberculosis (m. tuberculosis) infection. this study is aimed at the detection of association of m. tuberculos ...201525657155
in vitro activities of linezolid against clinical isolates of mycobacterium tuberculosis from shenyang, north of china. 201525657144
extra pulmonary tuberculosis: rapid identification of mycobacterium tuberculosis grown in mycobacterium growth indicator tube 960 and lowenstein-jensen media, employing standard diagnostics bioline mycobacterium tuberculosis protein 64 antigen detection kit.investigation of extra pulmonary tuberculosis (eptb) in and around pondicherry is being carried out since august 2011 in our tertiary care super specialty hospital.201525657129
higher blood volumes improve the sensitivity of direct pcr diagnosis of blood stream tuberculosis among hiv-positive patients: an observation study.blood stream tuberculosis (tb), caused by mycobacterium tuberculosis (mtb) is common among hiv-positive patients, turning rapidly fatal unless detected and treated promptly. blood culture is currently the standard test for the detection of mtb in whole blood but results take weeks; patients deteriorate markedly and often die before a diagnosis of blood stream tb is made. rapid molecular tests on whole blood, with potential for same day diagnosis of blood stream tb usually show low sensitivity du ...201525656799
crystal structure of dehydratase component hadab complex of mycobacterial fas-ii pathway.fatty acid biosynthesis type ii in mycobacteria delivers the fatty acids required for mycolic acid synthesis. the pathway employs a unique maoc like β-hydroxyacyl-acp dehydratase hadab or hadbc heterodimer in the third step of the elongation cycle. here we report the crystal structure of the hadab complex determined using a pb-siras method. crystal structure aided with enzymatic study establishes the roles of hada as a scaffolding component and hadb as a catalytic component together indispensabl ...201525656575
the viability and protein expression of beijing/w lineage mycobacterium tuberculosis circulating in xinjiang, china.beijing/w lineage strains of mycobacterium tuberculosis spread faster than other strains, tend to be more virulent and frequently associated with drug resistance. in this study, to distinguish the characteristics of beijing/w lineage and non-beijing/w lineage m. tuberculosis, we assessed the growth between the two groups under conditions of hypoxia, nutrient starvation, and intracellular growth in murine macrophages. we also examined the dna, rna, and protein levels of 5 major m. tuberculosis pr ...201525656263
immunologic manifestations of autophagy.the broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. the immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. one of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and ...201525654553
improving the sensitivity of the xpert mtb/rif assay on sputum pellets by decreasing the amount of added sample reagent: a laboratory and clinical evaluation.the xpert mtb/rif (xpert) assay permits rapid near-patient detection of mycobacterium tuberculosis in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. we evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased xpert sensitivity co ...201525653410
comparison of mgit and myco/f lytic liquid-based blood culture systems for recovery of mycobacterium tuberculosis from pleural fluid.the specificities and sensitivities of the bactec mycobacterial growth indicator tube (mgit) system for the recovery of mycobacterium tuberculosis from pleural fluid are not statistically different than those of the myco/f lytic liquid culture system. the time to positivity is shorter in the mgit system (12.7 versus 20.7 days, respectively; p=0.007). the myco/f lytic culture system may be an alternative to the mgit system for diagnosing pleural tuberculosis.201525653400
[effects of mycobacterium tuberculosis antigen and anti-tcrγδ antibody on il-17 production of human γδt cells in polarization culture].to investigate the effects of mycobacterium tuberculosis heat-resistant antigen (mtb-hag) and anti-tcr γδ monoclonal antibody (mab) on the induction and differentiation of human il-17-producing γδt cells under polarization culture conditions.201525652865
[mir-144 regulates bcg- and rapamycin-induced autophagy by targeting atg4a in raw264.7 cells].to study the effect of bacilli calmette-guerin (bcg) on mirnas (mir-21, mir-181a, mir-155 and mir-144) in raw264.7 cells, and with mir-144 as an example, to verify the relationship of mir-144 and atg4a, an autophagy-related gene, and study the mechanism underlying the regulatory effect of mir-144 on autophagy in the process of mycobacterium tuberculosis infection.201525652854
total and semi-syntheses of antimicrobial thuggacin derivatives.the total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium sorangium cellulosum, are reported. the thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards mycobacterium tuberculosis. this study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins a-c, 2) the roles of the thiazole ring, and 3) the hexyl side chain ...201525652819
mycobacterium tuberculosis dormancy-associated antigen of rv2660c induces stronger immune response in latent mycobacterium tuberculosis infection than that in active tuberculosis in a chinese population.one-third of the world's human population is latently infected with mycobacterium tuberculosis (m. tb), and adult tuberculosis (tb) is largely caused by the resuscitation of latent m. tb. rv2660c, an m. tb dormancy-related antigen, is preferentially expressed during latent infection. identification and characterization of rv2660c are crucial to understanding host-pathogen interactions and to develop drug target and vaccine candidates. in this study, t-cell and antibody immune responses against r ...201525652607
synchronous oral paracoccidioidomycosis and pulmonary tuberculosis in an immunocompetent patient.paracoccidioidomycosis (pcm) and tuberculosis (tb) are chronic granulomatous infectious diseases, in which the main form of contraction is through inhalation of the microorganism-paracoccidioides brasiliensis and mycobacterium tuberculosis. oral involvement of pcm is observed in up to 70 % of the cases and usually presents clinically as ulcerations with granular surface showing tiny hemorrhagic areas. oral presentation of tb is rare with prevalence smaller than 0.5 % of all cases. clinical prese ...201525652419
potential inhibitors for isocitrate lyase of mycobacterium tuberculosis and non-m. tuberculosis: a summary.isocitrate lyase (icl) is the first enzyme involved in glyoxylate cycle. many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (tca cycle), especially mycobacterium tuberculosis (mtb). in fact, icl is a potential drug target for mtb in dormancy. with the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and hiv-coinfection, the pace of drug discovery has to be increased. t ...201525649791
comprehensive insights into transcriptional adaptation of intracellular mycobacteria by microbe-enriched dual rna sequencing.the human pathogen mycobacterium tuberculosis has the capacity to escape eradication by professional phagocytes. during infection, m. tuberculosis resists the harsh environment of phagosomes and actively manipulates macrophages and dendritic cells to ensure prolonged intracellular survival. in contrast to other intracellular pathogens, it has remained difficult to capture the transcriptome of mycobacteria during infection due to an unfavorable host-to-pathogen ratio.201525649146
human mesenchymal stem cells: new sojourn of bacterial pathogens.tuberculosis (tb), caused by mycobacterium tuberculosis (m. tuberculosis), is the leading infectious disease which claims one human life every 15-20s globally. the persistence of this deadly disease in human population can be attributed to the ability of the bacterium to stay in latent form. m. tuberculosis possesses a plethora of mechanisms not only to survive latently under harsh conditions inside the host but also modulate the host immune cells in its favour. various m. tuberculosis gene fami ...201525648374
tuberculosis as a cause or comorbidity of childhood pneumonia in tuberculosis-endemic areas: a systematic review.pneumonia is a major cause of morbidity and mortality in infants and children worldwide, with most cases occurring in tuberculosis-endemic settings. studies have emphasised the potential importance of mycobacterium tuberculosis in acute severe pneumonia in children as a primary cause or underlying comorbidity, further emphasised by the changing aetiological range with rollout of bacterial conjugate vaccines in high mortality settings. we systematically reviewed clinical and autopsy studies done ...201525648115
pleural fluid adenosine deaminase (pfada) in the diagnosis of tuberculous effusions in a low incidence population.previous studies have assessed the diagnostic ability of pleural fluid adenosine deaminase (pfada) in detecting tuberculous pleural effusions, with good specificity and sensitivity reported. however, in north western europe pfada is not routinely used in the investigation of a patient with an undiagnosed pleural effusion, mainly due to a lack of evidence as to its utility in populations with low mycobacterium tuberculosis (mtb) incidence.201525647479
highly reproducible absolute quantification of mycobacterium tuberculosis complex by digital pcr.digital pcr (dpcr) offers absolute quantification through the limiting dilution of template nucleic acid molecules and has the potential to offer high reproducibility. however, the robustness of dpcr has yet to be evaluated using complex genomes to compare different dpcr methods and platforms. we used dna templates from the pathogen mycobacterium tuberculosis to evaluate the impact of template type, master mixes, primer pairs and, crucially, extraction methods on dpcr performance. performance wa ...201525646934
the pleiotropic transcriptional response of mycobacterium tuberculosis to vitamin c is robust and overlaps with the bacterial response to multiple intracellular stresses.mycobacterium tuberculosis (mtb) owes its success as a pathogen in large measure to its ability to exist in a persistent state of 'dormancy' resulting in a lifelong latent tuberculosis (tb) infection. an understanding of bacterial adaptation during dormancy will help in devising approaches to counter latent tb infection. in vitro models have provided valuable insights into bacterial adaptation; however, they have limitations because they do not disclose the bacterial response to the intracellula ...201525645949
the uptake of trehalose glycolipids by macrophages is independent of mincle.trehalose glycolipids play an important role in the pathogenesis of mycobacterium tuberculosis and are used as adjuvants for vaccines; however, much still remains unanswered about the mechanisms through which these glycolipids exert their immunomodulatory potential. recently, the macrophage-inducible c-type lectin mincle was determined to be the receptor for trehalose glycolipids, yet the role played by mincle in glycolipid uptake is unknown. accordingly, we developed several fluorescent trehalo ...201525645884
tuberculous spondylitis in russia and prominent role of multidrug-resistant clone mycobacterium tuberculosis beijing b0/w148.extrapulmonary and, in particular, spinal tuberculosis (tb) constitutes a minor but significant part of the total tb incidence. in spite of this, almost no studies on the genetic diversity and drug resistance of mycobacterium tuberculosis isolates from spinal tb patients have been published to date. here, we report results of the first russian and globally largest molecular study of m. tuberculosis isolates recovered from patients with tuberculous spondylitis (tbs). the majority of 107 isolates ...201525645851
a novel antimycobacterial compound acts as an intracellular iron chelator.efficient iron acquisition is crucial for the pathogenesis of mycobacterium tuberculosis. mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. resistance mutations against a novel pyrazolopyrimidinone compound (pzp) that is active against m. tuberculosis have been identified within the gene cluster encoding the esx-3 type vii secretion system. esx-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, ...201525645825
characterization of novel acyl coenzyme a dehydrogenases involved in bacterial steroid degradation.the acyl coenzyme a (acyl-coa) dehydrogenases (acads) fade34 and casc, encoded by the cholesterol and cholate gene clusters of mycobacterium tuberculosis and rhodococcus jostii rha1, respectively, were successfully purified. both enzymes differ from previously characterized acads in that they contain two fused acyl-coa dehydrogenase domains in a single polypeptide. site-specific mutagenesis showed that only the c-terminal acad domain contains the catalytic glutamate base required for enzyme acti ...201525645564
delamanid (opc-67683) for treatment of multi-drug-resistant tuberculosis.the research and development of delamanid was carried out by otsuka pharmaceutical development and commercialization (osaka, tokyo, japan). it belongs to the group of nitroimidazoles. it inhibits the synthesis of mycolic acids, crucial component of the cell wall of the mycobacterium tuberculosis complex. it is insoluble in water and its activity was proven in several in vitro and in vivo studies. its market approval was obtained in april 2014 in europe. its bactericidal activity was demonstrated ...201525645397
lspa gene of mycobacterium tuberculosis co-transcribes with rv1540 and induced by surface and acidic stress.lipoprotein signal peptidase, lspa (rv1539), is the only known gene in mycobacterial genome for cleaving the signal sequence from prolipoprotein to form mature lipoprotein. it has been implicated in maintaining the virulence of mycobacterium tuberculosis. the regulation of lspa had not been studied so far. here, we identify a novel operon lspa-rv1540 in m. tuberculosis. we detected co-transcription of the open reading frames of lspa-rv1540 in in-vitro as well as in ex-vivo conditions. analysis o ...201525644771
molecular insights into the binding of coenzyme f420 to the conserved protein rv1155 from mycobacterium tuberculosis.coenzyme f420 is a deazaflavin hydride carrier with a lower reduction potential than most flavins. in mycobacterium tuberculosis (mtb), f420 plays an important role in activating pa-824, an antituberculosis drug currently used in clinical trials. although f420 is important to mtb redox metabolism, little is known about the enzymes that bind f420 and the reactions that they catalyze. we have identified a novel f420 -binding protein, rv1155, which is annotated in the mtb genome sequence as a putat ...201525644473
triazole: a promising antitubercular agent.tuberculosis is a contagious disease with comparatively high mortality worldwide. the statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. the literature reveals th ...201525643871
a new butenolide cinnamate and other biological active chemical constituents from polygonum glabrum.phytochemical investigation of the methanol extract of the aerial parts of polygonum glabrum afforded one new natural product (-)-2-methoxy-2-butenolide-3-cinnamate (1) along with six known compounds, β-hydroxyfriedalanol (2), 3-hydroxy-5-methoxystilbene (3), (-) pinocembrin (4), sitosterol-(6'-o-palmitoyl)-3-o-β-d-glucopyranoside (5), (-) pinocembrin-5-methyl ether (6) and sitosterol-3-o-β-d-glucopyranoside (7). compound 1 showed promising in vitro anti-hiv-1 activity against primary isolates h ...201525643642
prisons as reservoir for community transmission of tuberculosis, brazil.we conducted a population-based study of tuberculosis (tb) cases in dourados, brazil, to assess the relationship between incarceration and tb in the general population. incarceration was associated with tb in an urban population; 54% of mycobacterium tuberculosis strains were related to strains from persons in prisons. tb control in prisons is critical for reducing disease prevalence.201525642998
mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system.mycobacterium tuberculosis ptpa, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. here we found that ptpa suppressed innate immunity dependent on pathways of the kinases jnk and p38 and the transcription factor nf-κb by exploiting host ubiquitin. binding of ptpa to ubiquitin via a region with no homology to human proteins activated it to deph ...201525642820
little difference between minimum inhibitory concentrations of mycobacterium tuberculosis wild-type organisms determined with bactec mgit 960 and middlebrook 7h10.the mic wild-type (wt) distribution for mycobacterium tuberculosis in bactec 960 mgit is not defined, which may result in poor reproducibility for drug susceptibility testing (dst), as several dst methods with different breakpoints are in use. in a comparison between mgit and middlebrook 7h10 medium of seven first- and second-line drugs, including 133 mic determinations of 15 wt isolates, we found an agreement of 91.7% within ± one mic dilution step. the results confirm the agreement in mic test ...201525640156
anti-mycobacterial activity of tamoxifen against drug-resistant and intra-macrophage mycobacterium tuberculosis.recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (mdr) tuberculosis and extensively drug-resistant (xdr) tuberculosis. we evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drug-sensitive or resistant strains of mycobacterium tuberculosis (tb), and the active intracellular killing of tamoxifen on tb in macrophages. the re ...201525639719
reduction of mycobacterium tuberculosis infection in bacillus calmette guerin immunized people is due to training of innate immunity.the currently used vaccine for prevention of tuberculosis is bacillus calmette guerin, which has been associated with a protective effect of 51% against tuberculosis. new vaccination strategies based on an enhancement of adaptive t-cell based immunity have been unsuccessful in increasing the efficiency of bcg immunisation. the proposed hypothesis is that a reduction of mycobacterium (m.) tuberculosis infection in bacillus calmette guerin immunized people is due to training of innate immunity. ev ...201525639709
mycobacterium tuberculosis reca is indispensable for inhibition of the mitogen-activated protein kinase-dependent bactericidal activity of thp-1-derived macrophages in vitro.our knowledge about the mechanisms utilized by mycobacterium tuberculosis to survive inside macrophages is still incomplete. one of the mechanism that protects m. tuberculosis from the host's microbicidal products and allows bacteria to survive involves dna repair systems such as the homologous recombination (hr) and nonhomologous end-joining (nhej) pathways. it is accepted that any pathway that contributes to genome maintenance should be considered as potentially important virulence factor. in ...201525639683
antitubercular activity of ru (ii) isoniazid complexes.despite the resistance developed by the mycobacterium tuberculosis (mtb) strains, isoniazid (inh) has been recognized as one of the best drug for treatment of tuberculosis (tb). the coordination of inh to ruthenium metal centers was investigated as a strategy to enhance the activity of this drug against the sensitive and resistant strains of mtb. the complexes trans-[ru(nh3)4(l)(inh)](2+) (l=so2 or nh3) were isolated and their chemical and antituberculosis properties studied. the minimal inhibit ...201525638418
virtual screening for the identification of novel inhibitors of mycobacterium tuberculosis cell wall synthesis: inhibitors targeting rmlb and rmlc.tuberculosis remains one of the deadliest infectious diseases in humans. it has caused more than 100 million deaths since its discovery in 1882. currently, more than 5 million people are infected with tb bacterium each year. the cell wall of mycobacterium tuberculosis plays an important role in maintaining the ability of mycobacteria to survive in a hostile environment. therefore, we report a virtual screening (vs) study aiming to identify novel inhibitors that simultaneously target rmlb and rml ...201525637777
interferon γ and tumor necrosis factor are not essential parameters of cd4+ t-cell responses for vaccine control of tuberculosis.mycobacterium tuberculosis infects one third of the world's population and causes >8 million cases of tuberculosis annually. new vaccines are necessary to control the spread of tuberculosis. t cells, interferon γ (ifn-γ), and tumor necrosis factor (tnf) are necessary to control m. tuberculosis infection in both humans and unvaccinated experimental animal models. however, the immune responses necessary for vaccine efficacy against m. tuberculosis have not been defined. the multifunctional activit ...201525637347
identifying essential genes in mycobacterium tuberculosis by global phenotypic profiling.transposon sequencing (tnseq) is a next-generation deep sequencing-based method to quantitatively assess the composition of complex mutant transposon libraries after pressure from selection. although this method can be used for any organism in which transposon mutagenesis is possible, this chapter describes its use in mycobacterium tuberculosis. more specifically, the methods for generating complex libraries through transposon mutagenesis, design of selective pressure, extraction of genomic dna, ...201525636614
iron acquisition strategies in mycobacteria.iron is an essential element to most life forms including mycobacterial species. however, in the oxidative atmosphere iron exists as insoluble salts. free and soluble iron ions are scarce in both the extracellular and intracellular environment which makes iron assimilation very challenging to mycobacteria. tuberculosis, caused by the pathogen, mycobacterium tuberculosis, is one of the most infectious and deadly diseases in the world. extensive studies regarding iron acquisition strategies have b ...201525636179
design of novel mycobacterium tuberculosis pantothenate synthetase inhibitors: virtual screening, synthesis and in vitro biological activities.pantothenate synthetase (ps) enzyme involved in the pantothenate biosynthetic pathway is essential for the virulence and persistent growth of mycobacterium tuberculosis (mtb). it is encoded by the panc gene, and has become an appropriate target for developing new therapeutics for tuberculosis. here we report new inhibitors active against mtb ps developed using energy based pharmacophore modelling of the available proteininhibitor complex (3ivx) and virtual screening of a large commercial librar ...201527490037
a virtual screen discovers novel, fragment-sized inhibitors of mycobacterium tuberculosis inha.isoniazid (inh) is usually administered to treat latent mycobacterium tuberculosis (mtb) infections and is used in combination therapy to treat active tuberculosis (tb). unfortunately, resistance to this drug is hampering its clinical effectiveness. inh is a prodrug that must be activated by mtb catalase-peroxidase (katg) before it can inhibit inha (mtb enoyl-acyl-carrier-protein reductase). isoniazid-resistant cases of tb found in clinical settings usually involve mutations in or deletion of ka ...201525636146
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