Publications

mycobacterium tuberculosis response regulators, devr and narl, interact in vivo and co-regulate gene expression during aerobic nitrate metabolism.	mycobacterium tuberculosis genes rv0844c/rv0845 encoding the narl response regulator and nars histidine kinase are hypothesized to constitute a two-component system involved in the regulation of nitrate metabolism. however, there is no experimental evidence to support this. in this study, we established m. tuberculosis narl/nars as a functional two-component system and identified his(241) and asp(61) as conserved phosphorylation sites in nars and narl, respectively. transcriptional profiling bet ...	2015	25659431
a rho gdp dissociation inhibitor produced by apoptotic t-cells inhibits growth of mycobacterium tuberculosis.	in this study, we found that a subpopulation of cd4(+)cd25(+) (85% foxp3(+)) cells from persons with latent tuberculosis infection (ltbi) inhibits growth of m. tuberculosis (m. tb) in human monocyte-derived macrophages (mdms). a soluble factor, rho gdp dissociation inhibitor (d4gdi), produced by apoptotic cd4(+)cd25(+) (85% foxp3(+)) cells is responsible for this inhibition of m. tb growth in human macrophages and in mice. m. tb-expanded cd4(+c)d25(+)foxp3(+)d4gdi(+) cells do not produce il-10, ...	2015	25659138
revealing hidden clonal complexity in mycobacterium tuberculosis infection by qualitative and quantitative improvement of sampling.	the analysis of microevolution events, its functional relevance and impact on molecular epidemiology strategies, constitutes one of the most challenging aspects of the study of clonal complexity in infection by mycobacterium tuberculosis. in this study, we retrospectively evaluated whether two improved sampling schemes could provide access to the clonal complexity that is undetected by the current standards (analysis of one isolate from one sputum). we evaluated in 48 patients the analysis by my ...	2015	25658553
disruption of an m. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice.	the identification of mycobacterium tuberculosis genes necessary for persistence in vivo provides insight into bacterial biology as well as host defense strategies. we show that disruption of m. tuberculosis membrane protein perm (rv0955) resulted in an ifn-γ-dependent persistence defect in chronic mouse infection despite the mutant's near normal growth during acute infection. the perm mutant required increased magnesium for replication and survival; incubation in low magnesium media resulted in ...	2015	25658098
mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in amhara region, ethiopia.	recent genotyping studies of mycobacterium tuberculosis in ethiopia have reported the identification of a new phylogenetically distinct m. tuberculosis lineage, lineage 7. we therefore investigated the genetic diversity and association of specific m. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary tb patients in the amhara region, ethiopia. dna was isolated from m. tuberculosis-positive sputum specimens (n=240) and analyzed by pcr and 24-locus mycobacterial in ...	2015	25673798
clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases.	the treatment of drug-resistant tuberculosis cases is challenging, as drug options are limited, and the existing diagnostics are inadequate. whole-genome sequencing (wgs) has been used in a clinical setting to investigate six cases of suspected extensively drug-resistant mycobacterium tuberculosis (xdr-tb) encountered at a london teaching hospital between 2008 and 2014. sixteen isolates from six suspected xdr-tb cases were sequenced; five cases were analyzed in a clinically relevant time frame, ...	2015	25673793
linking carbon metabolism to carotenoid production in mycobacteria using raman spectroscopy.	bacteria can utilize multiple sources of carbon for growth, and for pathogenic bacteria like mycobacterium tuberculosis, this ability is crucial for survival within the host. in addition, phenotypic changes are seen in mycobacteria grown under different carbon sources. in this study, we use raman spectroscopy to analyze the biochemical components present in m. smegmatis cells when grown in three differently metabolized carbon sources. our results show that carotenoid biosynthesis is enhanced whe ...	2015	25673658
role of multiplex polymerase chain reaction using is6110 and protein b for the diagnosis of extra-pulmonary tuberculosis: north india.	prompt and accurate diagnosis of extra-pulmonary tuberculosis (tb) is highly challenging. current conventional techniques lack sensitivity and are time-consuming. here, we report our experience with multiplex polymerase chain reaction (mpcr) using two targets namely is6110 and protein antigen b in the diagnosis of extra-pulmonary tb.	2015	25673587
a first insight on the population structure of mycobacterium tuberculosis complex as studied by spoligotyping and miru-vntrs in santiago, chile.	tuberculosis (tb) remains a significant public health problem worldwide, but the ecology of the prevalent mycobacterial strains, and their transmission, can vary depending on country and region. chile is a country with low incidence of tb, that has a geographically isolated location in relation to the rest of south american countries due to the andes mountains, but recent migration from neighboring countries has changed this situation. we aimed to assess the genotypic diversity of mycobacterium ...	2015	25671320
a proportion of mutations fixed in the genomes of in vitro selected isogenic drug-resistant mycobacterium tuberculosis mutants can be detected as minority variants in the parent culture.	we studied genomic variation in a previously selected collection of isogenic mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferring mutations, that were fixed in the genomes of six monoresistant strains. eight loci, present as minority variants (five non-synonymous, three synonym ...	2015	25670707
synthesis of new generation triazolyl- and isoxazolyl-containing 6-nitro-2,3-dihydroimidazooxazoles as anti-tb agents: in vitro, structure-activity relationship, pharmacokinetics and in vivo evaluation.	the nitroimidazole scaffold has attracted great interest in the last decade, which ultimately led to the discovery of the successful drug delamanid for multi-drug resistant tuberculosis (mdr-tb). herein, we report medicinal chemistry on a 6-nitro-2,3-dihydroimidazooxazole (nhio) scaffold with sar on the novel series of triazolyl- and isoxazolyl-based nhio compounds. in the present study, 41 novel triazolyl- and isoxazolyl-based nhio compounds were synthesized and evaluated against mycobacterium ...	2015	25670502
structural insight into mycobacterium tuberculosis maltosyl transferase inhibitors: pharmacophore-based virtual screening, docking, and molecular dynamics simulations.	pharmacophore-based virtual screening, subsequent docking, and molecular dynamics (md) simulations have been done to identify potential inhibitors of maltosyl transferase of mycobacterium tuberculosis (mtb glge). ligand and structure-based pharmacophore models representing its primary binding site (pbs) and unique secondary binding site 2 (sbs2), respectively, were constructed based on the three dimensional structure of mtb glge. these pharmacophore models were further used for screening of zinc ...	2015	25669125
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 ...	2015	25667654
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 ...	2015	25667413
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 ...	2015	25666821
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 ...	2015	25666798
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 ...	2015	25666036
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 ...	2015	25665034
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.	2015	25678973
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 ...	2015	25678771
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.	2015	25677402
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 ...	2015	25677256
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 ...	2015	25676890
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 ...	2015	25676469
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 ...	2015	25675247
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 ...	2015	25674511
population pharmacokinetics of rifampin in the treatment of mycobacterium tuberculosis in asian elephants.	the objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 asian elephants. the population pharmacokinetic models were created using monolix (version 4.2). simulations were conducted using modelrisk. we examined the influence of age, food, sex, and weight as model covariates. we further optimized the dosing of rifampin based upon simulatio ...	2015	25236765
a workplace tuberculosis case investigation in the presence of immigrant contacts from high prevalence countries.	the highest prevalence of tuberculosis (tb) occurs in foreign born immigrants in the united states. contact investigations at work sites with mostly immigrant workers present multiple practical problems. recently 402 contacts were investigated at a meat packing plant in rural texas by the texas department of state health services (dshs). our objective was to study the approach and effectiveness of this intensive investigation. we reviewed information, including symptoms, bcg status, tb history, ...	2015	25236657
design and structural analysis of aromatic inhibitors of type ii dehydroquinase from mycobacterium tuberculosis.	3-dehydroquinase, the third enzyme in the shikimate pathway, is a potential target for drugs against tuberculosis. whilst a number of potent inhibitors of the mycobacterium tuberculosis enzyme based on a 3-dehydroquinate core have been identified, they generally show little or no in vivo activity, and were synthetically complex to prepare. this report describes studies to develop tractable and drug-like aromatic analogues of the most potent inhibitors. a range of carbon-carbon linked biaryl anal ...	2015	25234229
a study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis.	in the present study, the use of dogs with experimental autoimmune encephalomyelitis (eae) as a disease model for necrotizing encephalitis (ne) was assessed. twelve healthy dogs were included in this study. canine forebrain tissues (8 g), including white and grey matter, were homogenized with 4 ml of phosphate-buffered saline for 5 min in an ice bath. the suspension was emulsified with the same volume of freund's complete adjuvant containing 1 mg/ml of killed mycobacterium tuberculosis h37ra. un ...	2015	25269720
discovery of a capuramycin analog that kills nonreplicating mycobacterium tuberculosis and its synergistic effects with translocase i inhibitors.	capuramycin (1) and its analogs are strong translocase i (murx/mray) inhibitors. in our structure-activity relationship studies of capuramycin analogs against mycobacterium tuberculosis (mtb), we observed for the first time that a capuramycin analog, ut-01320 (3) killed nonreplicating (dormant) mtb at low concentrations under low oxygen conditions, whereas selective murx inhibitors killed only replicating mtb under aerobic conditions. interestingly, 3 did not exhibit murx enzyme inhibitory activ ...	2015	25269459
mycobacterium genotypes in pulmonary tuberculosis infections and their detection by trained african giant pouched rats.	tuberculosis (tb) diagnosis in low-income countries is mainly done by microscopy. hence, little is known about the diversity of mycobacterium spp. in tb infections. different genotypes or lineages of mycobacterium tuberculosis vary in virulence and induce different inflammatory and immune responses. trained cricetomys rats show a potential for rapid diagnosis of tb. they detect over 28 % of smear-negative, culture-positive tb. however, it is unknown whether these rats can equally detect sputa fr ...	2015	25274413
allosteric regulation of the partitioning of glucose-1-phosphate between glycogen and trehalose biosynthesis in mycobacterium tuberculosis.	mycobacterium tuberculosis is a pathogenic prokaryote adapted to survive in hostile environments. in this organism and other gram-positive actinobacteria, the metabolic pathways of glycogen and trehalose are interconnected.	2015	25277548
bcg and infection with mycobacterium tuberculosis.		2015	25280583
a rapid and non-invasive 2-step algorithm for diagnosing tuberculous peritonitis using a t cell-based assay on peripheral blood and peritoneal fluid mononuclear cells together with peritoneal fluid adenosine deaminase.	a recently developed rd-1 gene-based assay for diagnosing tuberculous peritonitis (tbp) has given promising results. we therefore created a clinical algorithm for differentiating tbp from other diagnoses using peripheral blood and peritoneal fluid mononuclear cells (pbmc/pf-mc) along with conventional tests.	2015	25305499
aid tb resistance line probe assay for rapid detection of resistant mycobacterium tuberculosis in clinical samples.	to determine the sensitivity and specificity of aid tb resistance line probe assay (aid diagnostika, germany) to detect mycobacterium tuberculosis and its resistance to first- and second-line drugs in clinical samples using bactec 460tb as the reference standard.	2015	25305498
[tuberculosis prevention].	tuberculosis prevention is classically based on early detection of potential contagious cases and their effective treatment. but due to new parameters such as migration flows around the world, the emergence of mycobacterium tuberculosis resistant strains and the increase of the population at risk, screening should be more active and target those who are more vulnerable to developing the disease. traditional screening methods such as chest x-ray and tuberculin skin test, due to their high sensiti ...	2015	25282572
the diagnostic accuracy of tests for latent tuberculosis infection in hemodialysis patients: a systematic review and meta-analysis.	reactivation of latent mycobacterium tuberculosis infection is an important health concern for patients on hemodialysis because of their immunosuppressed state and in kidney transplant patients receiving immunosuppressive therapy to prevent organ rejection. there are several tests available to determine the presence of latent tuberculosis infection: the tuberculin skin test (tst), quantiferon-tb gold (qft-g), and t-spot.tb. the objective of this study is to evaluate the diagnostic accuracy of th ...	2015	25286055
host immune response to tuberculous meningitis.	tuberculous meningitis (tbm) is a severe complication of tuberculosis predominantly affecting young children. early treatment is vital to prevent morbidity and mortality, emphasizing the importance of early diagnosis. the lack of sensitive methods for early diagnosis is the most common cause of delay. attempts have been made to develop simplified tests for tuberculosis, but their diagnostic power remains poor. the clinical picture of tbm is mainly driven by the host's immune response to mycobact ...	2015	25301213
relative value of immunohistochemistry in detection of mycobacterial antigen in suspected cases of tuberculosis in tissue sections.	the diagnosis of tuberculosis (tb) depends on identification of the infecting organism. the diagnosis presents as a challenge due to its diverse clinical presentation and low yield of acid-fast bacilli (afb) in tissue sections.	2015	25308009
the conserved hypothetical protein rv0574c is required for cell wall integrity, stress tolerance, and virulence of mycobacterium tuberculosis.	the virulence of mycobacterium tuberculosis is intimately related to its distinctive cell wall. the biological significance of poly-α-l-glutamine (plg), a component in the cell wall of virulent mycobacteria, has not been explored adequately. the focus of this study is to investigate the role of a locus, rv0574c, coding for a polyglutamate synthase-like protein, in the synthesis of poly-α-l-glutamine in the context of mycobacterial virulence. evaluation of rv0574c gene expression in m. tuberculos ...	2015	25312955
interaction of pattern recognition receptors with mycobacterium tuberculosis.	tuberculosis (tb) is considered a major worldwide health problem with 10 million new cases diagnosed each year. our understanding of tb immunology has become greater and more refined since the identification of mycobacterium tuberculosis (mtb) as an etiologic agent and the recognition of new signaling pathways modulating infection. understanding the mechanisms through which the cells of the immune system recognize mtb can be an important step in designing novel therapeutic approaches, as well as ...	2015	25312698
doss is required for the complete virulence of mycobacterium tuberculosis in mice with classical granulomatous lesions.	mycobacterium tuberculosis (mtb) must counter hypoxia within granulomas to persist. dosr, in concert with sensor kinases doss and dost, regulates the response to hypoxia. yet mtb lacking functional dosr colonize the lungs of c57bl/6 mice, presumably owing to the lack of organized lesions with sufficient hypoxia in that model. we compared the phenotype of the δ-dosr, δ-doss, and δ-dost mutants to mtb using c3heb/fej mice, an alternate mouse model where lesions develop hypoxia. c3heb/fej mice were ...	2015	25322074
impact of nonlinear interactions of pharmacokinetics and mics on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis.	the relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex and nonlinear. in patients on treatment, an analysis of the rate of decline in the sputum bacillary burden reveals two slopes. the first is the α-slope, which is thought to reflect bactericidal effect, followed by a β-slope, which is thought to reflect sterilizing activity. we sought to characterize the effects of standard first-line treatment on sterilizing activity. ...	2015	25313213
early dynamics of t helper cell cytokines and t regulatory cells in response to treatment of active mycobacterium tuberculosis infection.	biomarkers that can identify tuberculosis (tb) disease and serve as markers for efficient therapy are requested. we have studied t cell cytokine production [interferon (ifn)-γ, interleukin (il)-2, tumour necrosis factor (tnf)-α] and degranulation (cd107a) as well as subsets of cd4(+) t regulatory cells (tregs ) after in-vitro mycobacterium tuberculosis (mtb) antigen stimulation [early secretory antigenic target (esat)-6, culture filtrate protein (cfp)-10, antigen 85 (ag85)] in 32 patients with a ...	2015	25313008
classification of intraocular tuberculosis.	tuberculosis in the tb endemic countries commonly manifests in the eye as tuberculous uveitis. there is a wide spectrum of the clinical manifestations of intraocular tuberculosis (iotb). for want of any gold standard diagnostic tests or diagnostic criteria, the estimates of iotb prevalence have varied greatly. none of the previously suggested guidelines for diagnosis of iotb have been validated. we give definitions of clinical signs and diagnostic tests that have been used in the literature. bas ...	2015	25314361
cd11c(+) cd103(+) cells of mycobacterium tuberculosis-infected c57bl/6 but not of balb/c mice induce a high frequency of interferon-γ- or interleukin-17-producing cd4(+) cells.	the magnitude of the cellular adaptive immune response is critical for the control of mycobacterium tuberculosis infection in the chronic phase. in addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. in this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of cd4(+) populations generated after m. tuberculosis infection. thirty days post-in ...	2015	25322675
a bayesian nonlinear mixed-effects regression model for the characterization of early bactericidal activity of tuberculosis drugs.	trials of the early bactericidal activity (eba) of tuberculosis (tb) treatments assess the decline, during the first few days to weeks of treatment, in colony forming unit (cfu) count of mycobacterium tuberculosis in the sputum of patients with smear-microscopy-positive pulmonary tb. profiles over time of cfu data have conventionally been modeled using linear, bilinear, or bi-exponential regression. we propose a new biphasic nonlinear regression model for cfu data that comprises linear and bilin ...	2015	25322214
virulence factor senx3 is the oxygen-controlled replication switch of mycobacterium tuberculosis.	morphogenetic switching between the replicating and nonreplicating states of mycobacterium tuberculosis is regulated by oxygen, nitric oxide, and carbon monoxide levels. the mechanisms by which m. tuberculosis senses these diatomic gases remain poorly understood. in this study, we have examined whether virulence factor senx3 plays any role in oxygen sensing.	2015	25333974
in vitro and in vivo activities of the nitroimidazole tba-354 against mycobacterium tuberculosis.	nitroimidazoles are a promising new class of antitubercular agents. the nitroimidazo-oxazole delamanid (opc-67683, deltyba) is in phase iii trials for the treatment of multidrug-resistant tuberculosis, while the nitroimidazo-oxazine pa-824 is entering phase iii for drug-sensitive and drug-resistant tuberculosis. tba-354 (sn31354[(s)-2-nitro-6-((6-(4-trifluoromethoxy)phenyl)pyridine-3-yl)methoxy)-6,7-dihydro-5h-imidazo[2,1-b][1,3]oxazine]) is a pyridine-containing biaryl compound with exceptional ...	2015	25331696
verapamil increases the bactericidal activity of bedaquiline against mycobacterium tuberculosis in a mouse model.	bedaquiline is a newly approved drug for the treatment of multidrug-resistant tuberculosis, but there are concerns about its safety in humans. we found that the coadministration of verapamil with subinhibitory doses of bedaquiline gave the same bactericidal effect in mice as did the full human bioequivalent bedaquiline dosing. adding verapamil to bedaquiline monotherapy also protected against the development of resistant mutants in vivo. the adjunctive use of verapamil may permit use of lower do ...	2015	25331694
the rv1184c locus encodes chp2, an acyltransferase in mycobacterium tuberculosis polyacyltrehalose lipid biosynthesis.	trehalose glycolipids are found in many bacteria in the suborder corynebacterineae, but methyl-branched acyltrehaloses are exclusive to virulent species such as the human pathogen mycobacterium tuberculosis. in m. tuberculosis, the acyltransferase papa3 catalyzes the formation of diacyltrehalose (dat), but the enzymes responsible for downstream reactions leading to the final product, polyacyltrehalose (pat), have not been identified. the pat biosynthetic gene locus is similar to that of another ...	2015	25331437
delamanid when other anti-tuberculosis-treatment regimens failed due to resistance or tolerability.	the limited availability of effective drugs causes difficulties in the management of multidrug-resistant tuberculosis (mdr-tb) and novel therapeutic agents are needed. delamanid , a new nitro-hydro-imidazooxazole derivative, inhibits mycolic acid synthesis. this review covers the efficacy and safety of delamanid for mdr-tb.	2015	25327169
establishment of a new zealand rabbit model of spinal tuberculosis.	this was an experimental study.	2015	25325713
genotypic susceptibility testing of mycobacterium tuberculosis isolates for amikacin and kanamycin resistance by use of a rapid sloppy molecular beacon-based assay identifies more cases of low-level drug resistance than phenotypic lowenstein-jensen testing.	resistance to amikacin (amk) and kanamycin (kan) in clinical mycobacterium tuberculosis strains is largely determined by specific mutations in the rrs gene and eis gene promoter. we developed a rapid, multiplexed sloppy molecular beacon (smb) assay to identify these mutations and then evaluated assay performance on 603 clinical m. tuberculosis dna samples collected in south korea. assay performance was compared to gold-standard phenotypic drug susceptibility tests, including lowenstein-jensen (l ...	2015	25339395
use of transrenal dna for the diagnosis of extrapulmonary tuberculosis in children: a case of tubercular otitis media.	the diagnosis of tuberculosis (tb) is difficult in children, especially for smear-negative pulmonary and extrapulmonary tb, which are common at this age. we report an 11-year-old girl with tb otitis media with negative smear microscopy and xpert mtb/rif but positive mycobacterium tuberculosis-specific transrenal dna (tr-mtb-dna) test results and culture for m. tuberculosis.	2015	25339389
identification and genotyping of mycobacterium tuberculosis isolated from water and soil samples of a metropolitan city.	the potential role of environmental mycobacterium tuberculosis in the epidemiology of tb remains unknown. we investigated the transmission of m tuberculosis from humans to the environment and the possible transmission of m tuberculosis from the environment to humans.	2015	25340935
a molecular dynamics investigation of mycobacterium tuberculosis prenyl synthases: conformational flexibility and implications for computer-aided drug discovery.	with the rise in antibiotic resistance, there is interest in discovering new drugs active against new targets. here, we investigate the dynamic structures of three isoprenoid synthases from mycobacterium tuberculosis using molecular dynamics (md) methods with a view to discovering new drug leads. two of the enzymes, cis-farnesyl diphosphate synthase (cis-fpps) and cis-decaprenyl diphosphate synthase (cis-dpps), are involved in bacterial cell wall biosynthesis, while the third, tuberculosinyl ade ...	2015	25352216
evaluation of the usefulness of interferon-gamma release assays and the tuberculin skin test for the detection of latent mycobacterium tuberculosis infections in korean rheumatic patients who are candidates for biologic agents.	the aim of this study was to evaluate the occurrence of active tuberculosis (tb) in patients who received both an interferon-gamma release assay (the quantiferon-tb gold in-tube test [qft-git]) and tuberculin skin test (tst) in comparison with those who received qft-git or tst alone for the detection of latent tb infection (ltbi).	2015	25351815
ursolic acid activates intracellular killing effect of macrophages during mycobacterium tuberculosis infection.	tuberculosis is one of the most threatening infectious diseases to public health all over the world, for which mycobacterium tuberculosis (mtb) is the etiological agent of pathogenesis. ursolic acid (ua) has immunomodulatory function and exhibits antimycobacterial activity. however, the intracellular killing effect of ua has yet to be elucidated. the aim of this study was to evaluate the intracellular killing effect of ua during mycobacterial infection. the intracellular killing activity of ua w ...	2015	25406534
ultrasensitive electrochemical biosensing for dna using quantum dots combined with restriction endonuclease.	a universal and sensitive electrochemical biosensing platform for the detection and identification of dna using cdse quantum dots (cdse qds) as signal markers was designed. the detection mechanism was based on the specific recognition of mspi endonuclease combined with the signal amplification of gold nanoparticles (aunps). mspi endonuclease could recognize its specific sequence in the double-strand dna (dsdna) and cleave the dsdna fragments linked with cdse qds from the electrode. the remaining ...	2015	25408952
establishment of a rabbit model of spinal tuberculosis using mycobacterium tuberculosis strain h37rv.	this study aimed to establish a spinal tuberculosis model by implanting mycobacterium tuberculosis strain h37rv into the lumbar vertebral body of new zealand white rabbits. a hole was first drilled into the top of the 6th lumbar vertebra of each rabbit, which was then filled with a gelatin sponge to adsorb 0.2 ml of m. tuberculosis suspension (10(7) cfu /ml) for the infection group or normal saline for the control group. the holes were then closed with sutures. ct findings demonstrated that 5 an ...	2015	25420665
molecular epidemiology of mycobacterium tuberculosis among south african gold miners.	hiv-associated tuberculosis remains a major health problem among the gold-mining workforce in south africa. we postulate that high levels of recent transmission, indicated by strain clustering, are fueling the tuberculosis epidemic among gold miners.	2015	25419914
synthesis and antitubercular screening of some novel 4h-1,4- benzothiazines and their sulfones under environment benign solvent free conditions as future anti-tubercular agents.	some novel analogs of 4h-1,4-benzothiazines were synthesized under environmentally benign solvent free conditions by one pot oxidative cyclocondensation of substituted 2- aminobenzenthiols with compounds having active methylene group and then converted in to sulfones. these compounds were examined as antitubercular agents against mycobacterium tuberculosis h37rv using rema plate method. the best results have mics from 6.4 to 8.8 μg/ml, comparable to phenothiazines. ir, nmr and mass spectral inve ...	2015	25426761
the cyclic peptide ecumicin targeting clpc1 is active against mycobacterium tuberculosis in vivo.	drug-resistant tuberculosis (tb) has lent urgency to finding new drug leads with novel modes of action. a high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against m. tuberculosis in vitro, including nonreplicating cells. ecumicin retains activity against isolated multiple-drug-resistant (mdr) and extensively drug-resistant ...	2015	25421483
rapid cytolysis of mycobacterium tuberculosis by faropenem, an orally bioavailable β-lactam antibiotic.	recent clinical studies indicate that meropenem, a β-lactam antibiotic, is a promising candidate for therapy of drug-resistant tuberculosis. however, meropenem is chemically unstable, requires frequent intravenous injection, and must be combined with a β-lactamase inhibitor (clavulanate) for optimal activity. here, we report that faropenem, a stable and orally bioavailable β-lactam, efficiently kills mycobacterium tuberculosis even in the absence of clavulanate. the target enzymes, l,d-transpept ...	2015	25421469
evaluation of two commercial nucleic acid amplification kits for detecting mycobacterium tuberculosis in saliva samples.	the objective of this study was to evaluate the efficacy of two commercial nucleic acid amplification techniques to identify mycobacterium tuberculosis in saliva.	2015	25421014
2-carboxyquinoxalines kill mycobacterium tuberculosis through noncovalent inhibition of dpre1.	phenotypic screening of a quinoxaline library against replicating mycobacterium tuberculosis led to the identification of lead compound ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). with an mic99 and mbc of 3.1 μm, ty38c is bactericidal and active against intracellular bacteria. to investigate its mechanism of action, we isolated mutants resistant to ty38c and sequenced their genomes. mutations were found in rv3405c, coding for the transcriptional repressor ...	2015	25427196
structural basis for targeting the ribosomal protein s1 of mycobacterium tuberculosis by pyrazinamide.	pyrazinamide (pza) is a first-line drug for tuberculosis (tb) treatment and is responsible for shortening the duration of tb therapy. the mode of action of pza remains elusive. rpsa, the ribosomal protein s1 of mycobacterium tuberculosis (mtb), was recently identified as a target of pza based on its binding activity to pyrazinoic acid (poa), the active form of pza. poa binding to rpsa led to the inhibition of trans-translation. however, the nature of the rpsa-poa interaction remains unknown. key ...	2015	25430994
the mycobacterium tuberculosis clp gene regulator is required for in vitro reactivation from hypoxia-induced dormancy.	mycobacterium tuberculosis (mtb) is the leading cause of death from an infectious disease worldwide and is the causative agent of tuberculosis (chao, m. c., and rubin, e. j. (2010) annu. rev. microbiol. 64, 293-311). throughout infection, mtb encounters a variety of host pressures. thus, responding to these host stresses via the induction of multiple regulatory networks is needed for survival within the host. the clp protease gene regulator, rv2745c (clgr), is induced in response to environmenta ...	2015	25422323
evaluation of the cobas taqman mtb test for the detection of mycobacterium tuberculosis complex according to acid-fast-bacillus smear grades in respiratory specimens.	we evaluated the performance of the cobas taqman mtb test (roche diagnostics, basel, switzerland), stratified by acid-fast bacilli (afb) smear grades. the sensitivity of this test in smear-positive specimens was >95% in all grades, while that in trace and negative specimens was 85.3% and 34.4%, respectively.	2015	25428157
pott's disease? aids-associated mycobacterium heckeshornense spinal osteomyelitis and diskitis.	acid-fast bacillus (afb) spinal osteomyelitis in a patient with aids is often presumed to be caused by reactivated mycobacterium tuberculosis. however, other afb pathogens can mimic m. tuberculosis and, to ensure appropriate and adequate therapy, should be considered by clinicians. we present a case of aggressive spinal osteomyelitis caused by mycobacterium heckeshornense in an aids patient; a review of the literature is also included.	2015	25428153
discrimination between active and latent tuberculosis based on ratio of antigen-specific to mitogen-induced ip-10 production.	mycobacterium tuberculosis is the major causative agent of tuberculosis (tb). the gamma interferon (ifn-γ) release assay (igra) has been widely used to diagnose tb by testing cell-mediated immune responses but has no capacity for distinguishing between active tb and latent tb infection (ltbi). this study aims to identify a parameter that will help to discriminate active tb and ltbi. whole-blood samples from 33 active tb patients, 20 individuals with ltbi, and 26 non-tb controls were applied to t ...	2015	25428147
high-throughput mycobacterial interspersed repetitive-unit-variable-number tandem-repeat genotyping for mycobacterium tuberculosis epidemiological studies.	the emergence of drug-resistant forms of tuberculosis (tb) represents a major public health concern. understanding the transmission routes of the disease is a key factor for its control and for the implementation of efficient interventions. mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (miru-vntr) marker typing is a well-described method for lineage identification and transmission tracking. however, the conventional manual genotyping technique is cumbersome and time-co ...	2015	25428144
a simple, single triplex pcr of is6110, is1081, and 23s ribosomal dna targets, developed for rapid detection and discrimination of mycobacterium from clinical samples.	tuberculosis (tb) is the most common mycobacterial infection in developing countries, requiring a rapid, accurate, and well-differentiated detection/diagnosis. for the rapid detection and discrimination of mycobacterium tuberculosis complex (mtc) from nontuberculous mycobacteria (ntm), a novel, simple, and primer-combined single-step multiplex pcr using three primer pairs (6110f-6110r, 1081f-1081r, and 23sf-23sr; annealing on each of is6110, is1081, and 23s rdna targets), hereafter referred to a ...	2015	25433552
reactivation of dormant "non-culturable" mycobacterium tuberculosis developed in vitro after injection in mice: both the dormancy depth and host genetics influence the outcome.	three stocks of mycobacterium tuberculosis h37rv were cultured in vitro under prolonged hypoxic or acidified conditions until partial or complete loss of the capacity to form colonies on agar medium was achieved. such dormant "non-culturable" mycobacteria were assessed for the growth resuscitation after intra-tracheal injection into mice of the two inbred strains with different genetic susceptibility to m. tuberculosis-triggered disease: hyper-susceptible i/st and relatively resistant b6. the re ...	2015	25434928
predicting the subcellular localization of mycobacterial proteins by incorporating the optimal tripeptides into the general form of pseudo amino acid composition.	mycobacterium tuberculosis is a bacterium that causes tuberculosis, one of the most prevalent infectious diseases. predicting the subcellular localization of mycobacterial proteins in this bacterium may provide vital clues for the prediction of protein function as well as for drug discovery and design. therefore, a computational method that can predict the subcellular localization of mycobacterial proteins with high precision is highly desirable. we propose a computational method to predict the ...	2015	25437899
role of ultrasound evaluation for the diagnosis and monitoring of thyroid tuberculosis: a case report and review of the literature.	thyroid tuberculosis (tt) is an extremely rare condition, with acute abscess formation being the most uncommon form of presentation. mycobacterium tuberculosis may affect the thyroid gland through hematogenous spread from an extra-thyroid focus of disease or by direct extension from adjacent cervical lymph nodes. due to the non-specific imaging findings and the variable clinical manifestations, tt is rarely diagnosed promptly prior to percutaneous biopsy or surgery. the present study reports the ...	2015	25435964
role of calcium channels in cellular antituberculosis effects: potential of voltage-gated calcium-channel blockers in tuberculosis therapy.	the immunity of human immune cells and their ability to inhibit mycobacterium tuberculosis (mtb) are key factors in the anti-mtb effect. however, mtb modulates the levels and activity of key intracellular second messengers, such as calcium, to evade protective immune responses. recent studies suggest that inhibiting l-type calcium channel in immune cells using either antibodies or small interfering rna increases calcium influx, upregulates the expression of proinflammation genes, and reduces mtb ...	2015	25442874
a comparative evaluation of the sensitivity of one automated and one manual nucleic acid extraction methods for the performance of the speed-oligo™ direct mycobacterium tuberculosis assay.		2015	25444042
a feasibility study of the xpert mtb/rif test at the peripheral level laboratory in china.	to evaluate the performance of xpert mtb/rif (mtb/rif) in the county-level tuberculosis (tb) laboratory in china.	2015	25447720
synergistic effect of muramyl dipeptide with heat shock protein 70 from mycobacterium tuberculosis on immune activation.	heat shock protein 70 from mycobacterium tuberculosis (mtb hsp70) has been known to modulate immune response including dendritic cell activation. muramyl dipeptide (mdp) is an immunoreactive derivative of peptidoglycan from all gram-negative and gram-positive bacteria and recognized to be responsible for function of freund's complete adjuvant. in this study, we evaluated effect of mdp on in vitro activation of bone marrow derived dendritic cells (bmdcs) and in vivo production of cytokines and ch ...	2015	25446399
evaluation of three rapid assays for mycobacterium tuberculosis complex detection in a comprehensive hospital from west china.	to assess the capacity of rapid and accurate confirmation of the mycobacterium tuberculosis complex (mtbc) in a chinese clinical laboratory.	2015	25444951
status of vitamin d, antimicrobial peptide cathelicidin and t helper-associated cytokines in patients with diabetes mellitus and pulmonary tuberculosis.	pulmonary tuberculosis (ptb) is a high burden infectious disease in china. the immune function is damaged in patients with diabetes mellitus (dm) who are easy to infect with mycobacterium tuberculosis (mtb). the growth of mtb has been shown to be restrained following the administration of vitamin d and antimicrobial peptide cathelicidin (ll-37); however, the effect in patients with dm and ptb remains unclear. vitamin d can regulate the immune system through vitamin d receptors expressed in t hel ...	2015	25452769
adjunctive biomarkers for improving diagnosis of tuberculosis and monitoring therapeutic effects.	to identify host biomarkers associated with latent tuberculosis infection (ltbi), active tuberculosis (tb), and nontuberculous mycobacteria (ntm) diseases to improve diagnosis and effective anti-tb treatment.	2015	25452040
automated liquid culture system misses isoniazid heteroresistance in mycobacterium tuberculosis isolates with mutations in the promoter region of the inha gene.	heteroresistance in mycobacterium tuberculosis isolates remains the major challenge for phenotypic drug susceptibility testing (dst) methods to detect drug resistance. the aim of this study was to investigate the abilities of phenotypic dst methods to identify the isoniazid (inh) heteroresistance in m. tuberculosis. we found that the broth dilution method was able to detect inh resistance if 0.5 % resistant bacteria with mutations in the katg and oxyr-ahpc regions were present, while the detecti ...	2015	25344830
the relationship between mycobacterium tuberculosis mgit time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations.	the relationship between cfu and mycobacterial growth indicator tube (mgit) time to positivity (ttp) is uncertain. we attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load.	2015	25344806
antimycobacterial efficacy of andrographis paniculata leaf extracts under intracellular and hypoxic conditions.	the inhibition of the growth of mycobacterium tuberculosis by the extracts of andrographis paniculata has been studied using intracellular and axenic hypoxic conditions. the inhibition (confirmed using the gold standard colony forming unit assay) was found to increase with "double stimuli" or higher concentration of the extract. organic solvent extracts were found to inhibit bacterial growth more than the aqueous extracts under microaerophilic conditions mimicked through axenic and intracellular ...	2015	25348959
roles of ala-149 in the catalytic activity of diadenosine tetraphosphate phosphorylase from mycobacterium tuberculosis h37rv.	diadenosine 5',5'''-p(1),p(4)-tetraphosphate (ap4a) phosphorylase from mycobacterium tuberculosis h37rv (mtapa) belongs to the histidine triad motif (hit) superfamily, but is the only member with an alanine residue at position 149 (ala-149). enzymatic analysis revealed that the ala-149 deletion mutant displayed substrate specificity for diadenosine 5',5'''-p(1),p(5)-pentaphosphate and was inactive on ap4a and other substrates that are utilized by the wild-type enzyme.	2015	25348769
high-content screening technology combined with a human granuloma model as a new approach to evaluate the activities of drugs against mycobacterium tuberculosis.	tuberculosis remains a major health problem due to the emergence of drug-resistant strains of mycobacterium tuberculosis. some models have provided valuable information about drug resistance and efficacy; however, the translation of these results into effective human treatments has mostly proven unsuccessful. in this study, we adapted high-content screening (hcs) technology to investigate the activities of antitubercular compounds in the context of an in vitro granuloma model. we observed signif ...	2015	25348525
key structures and interactions for binding of mycobacterium tuberculosis protein kinase b inhibitors from molecular dynamics simulation.	substituted aminopyrimidine inhibitors have recently been introduced as antituberculosis agents. these inhibitors show impressive activity against protein kinase b, a ser/thr protein kinase that is essential for cell growth of m. tuberculosis. however, up to now, x-ray structures of the protein kinase b enzyme complexes with the substituted aminopyrimidine inhibitors are currently unavailable. consequently, structural details of their binding modes are questionable, prohibiting the structural-ba ...	2015	25354564
diagnostic value of genechip for detection of resistant mycobacterium tuberculosis in patients with differing treatment histories.	the increasing burden of drug-resistant tuberculosis (tb) poses an escalating threat to national tb control programs. to assist appropriate treatment for tb patients, accurate and rapid detection of drug resistance is critical. the genechip test is a novel molecular tool for the diagnosis of tb drug resistance. performance-related data on genechip are limited, and evaluation in new and previously treated tb cases has never been performed. we evaluated the diagnostic performance of genechip in de ...	2015	25355771
diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic t lymphocytes in tuberculous pleural effusion.	early diagnosis of tuberculous pleural effusion (tpe) remains difficult. while some inflammatory markers in pleural effusion (pe) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic t lymphocytes have not been investigated.	2015	25355638
psts-1, the 38-kda mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis.	mycobacterium tuberculosis, the primary causative agent of tuberculosis, infects macrophages and transforms the hostile intracellular environment into a permissive niche. m. tuberculosis infects macrophages using a variety of microbial ligand/cell receptor systems. in this study, binding assays with biotin-labelled mycobacterial cell wall proteins revealed five concanavalin a-reactive proteins that bind macrophages. among these proteins, we identified psts-1, a 38-kda m. tuberculosis mannosylate ...	2015	25359607
peptide idr-1018: modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections.	host defense (antimicrobial) peptides, produced by all complex organisms, typically contain an abundance of positively charged and hydrophobic amino acid residues. a small synthetic peptide termed innate defense regulator (idr-)1018 was derived by substantial modification of the bovine neutrophil host defense peptide bactenecin. here, we review its intriguing properties that include anti-infective, anti-inflammatory, wound healing, and anti-biofilm activities. it was initially developed as an im ...	2015	25358509
combined use of mycobacterium tuberculosis-specific cd4 and cd8 t-cell responses is a powerful diagnostic tool of active tuberculosis.	immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. a multiparameter flow cytometry assay assessing t-cell responses specific to mycobacterium tuberculosis and the combination of both cd4 and cd8 t-cell responses accurately discriminated between active tuberculosis and latent infection.	2015	25362202
tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing.	whole-genome sequencing (wgs) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. we combined strain-specific single-nucleotide polymorphism (snp) typing and targeted wgs to investigate a tuberculosis cluster spanning 21 years in bern, switzerland.	2015	25362193
disparities in capreomycin resistance levels associated with the rrs a1401g mutation in clinical isolates of mycobacterium tuberculosis.	as the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance fo ...	2015	25385119
discovery of mycobacterium tuberculosis α-1,4-glucan branching enzyme (glgb) inhibitors by structure- and ligand-based virtual screening.	glgb (α-1,4-glucan branching enzyme) is the key enzyme involved in the biosynthesis of α-glucan, which plays a significant role in the virulence and pathogenesis of mycobacterium tuberculosis. because α-glucans are implicated in the survival of both replicating and non-replicating bacteria, there exists an exigent need for the identification and development of novel inhibitors for targeting enzymes, such as glgb, involved in this pathway. we have used the existing structural information of m. tu ...	2015	25384979
mycobacterium tuberculosis enoyl-acyl carrier protein reductase inhibitors as potential antituberculotics: development in the past decade.	mycobacterial enoyl-acp-reductase, an enzyme contributing in mycolic acids biosynthesis, has been established as promising target of novel antimycobacterial drugs. the development of inhibitors active without previous activation by catalase/peroxidase system (e.g. isoniazid), seems to be rational approach. catalase/peroxidase system is frequently responsible for resistance. we hereby present a review of direct mycobacterial enoyl-acyl carrier protein reductase inhibitors development in past deca ...	2015	25383419