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mhc ib molecule qa-1 presents mycobacterium tuberculosis peptide antigens to cd8+ t cells and contributes to protection against infection.a number of nonclassical mhc ib molecules recognizing distinct microbial antigens have been implicated in the immune response to mycobacterium tuberculosis (mtb). hla-e has been identified to present numerous mtb peptides to cd8+ t cells, with multiple hla-e-restricted cytotoxic t lymphocyte (ctl) and regulatory t cell lines isolated from patients with active and latent tuberculosis (tb). in other disease models, hla-e and its mouse homolog qa-1 can act as antigen presenting molecules as well as ...201728475642
first-time detection and identification of the mycobacterium tuberculosis complex members in extrapulmonary tuberculosis clinical samples in south tunisia by a single tube tetraplex real-time pcr assay.tunisia has one of the highest burdens of extrapulmonary tuberculosis (eptb) among tuberculosis (tb) cases but the contribution of mtbc-mediated human eptb is unknown. eptb diagnosis is challenging due to the paucibacillary nature of clinical samples. therefore, a need of a simplified molecular method for sensitive and specific tb detection and differentiation of mtbc members caused eptb remains a priority to an early diagnosis, optimize successful anti-tb treatment and minimize transmission. we ...201728475618
correction: intracellular growth of mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells. 201728475039
risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.mycobacterium tuberculosis (tb) is one of the world's most devastating public health threats. our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (nsaids) affect the risk of new incident active tb disease.201728472944
type-ii nadh dehydrogenase (ndh-2): a promising therapeutic target for antitubercular and antibacterial drug discovery.tuberculosis (tb) is highly dangerous due to the development of resistance to first-line drugs. moreover, mycobacterium tuberculosis (mtb) has also developed resistance to newly approved antitubercular drug bedaquiline. this necessitates the search for drugs acting on newer molecular targets. the energy metabolism of mycobacteria is the prime focus for the discovery of novel antitubercular drugs. targeting type-2 nadh dehydrogenase (ndh-2) involved in the production of respiratory atp could, the ...201728472892
clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis regimen.drug-resistant tuberculous meningitis (tbm) is difficult to diagnose and treat. mortality is high and optimal treatment is unknown. we compared clinical outcomes of drug-resistant and -susceptible tbm treated with either standard or intensified antituberculosis treatment.201728472255
copy number variation of fcgr genes in etiopathogenesis of sarcoidosis.we have previously revealed that, in contrast to polymorphism of fcgr2b and fcgr3b, polymorphism of fcgr2a, fcgr2c and fcgr3a genes, encoding receptors for fc fragment of immunoglobulin g (fcγ receptors), play a role in increased level of circulating immune complexes with occurrence of mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis. however, this immunocomplexemia might also be caused by decreased clearance by immune cells due to a changed copy number of fcgr genes. ...201728472129
performance of taqman array card to detect tb drug resistance on direct specimens.culture based phenotypic drug susceptibility testing (dst) for mycobacterium tuberculosis (tb) is time consuming therefore rapid genotypic methods are increasingly being utilized. we previously developed and evaluated on tb isolates a rapid genotypic taqman array card (tac) that detects mutations in several resistance-associated genes using dozens of primer pairs, probes, and high resolution melt analysis, with >96% accuracy versus sanger sequencing. in this study we examined the performance of ...201728472124
transcription factor rv0081 from mycobacterium tuberculosis: purification, crystallization and initial crystallographic analysis.because of its high infectivity and pathogenicity, mycobacterium tuberculosis is a serious threat to human health. while the transcription-regulatory system of m. tuberculosis remains incompletely understood, rv0081, an essential regulatory hub, is known to mediate the initial response to hypoxia in the long-term survival of m. tuberculosis. here, the production, crystallization and initial x-ray crystallographic analysis of rv0081 are reported. the crystals of rv0081 belonged to space group p62 ...201728471360
mycobacterium tuberculosis found at both skin lesions and mantoux testing site in a patient with erythema induratum of bazin.mycobacterium tuberculosis is very rarely found in erythema induratum of bazin; recently, we found an unusual case with positive acid-fast bacilli and polymerase chain reaction for detecting m. tuberculosis in both skin lesions of the extremities and the site of mantoux test.201728470727
novel adjuvant for immunization against tuberculosis: dna vaccine expressing mycobacterium tuberculosis antigen 85a and interleukin-15 fusion product elicits strong immune responses in mice.to investigate the potential of interleukin (il)-15 as a novel adjuvant for mycobacterium tuberculosis (mtb) antigen 85a (ag85a) vaccine.201728470626
clinical impact of nucleic acid amplification testing in the diagnosis of mycobacterium tuberculosis: a 10-year longitudinal study.nucleic acid amplification (naa) testing for mycobacterium tuberculosis (mtb) offers improved diagnostic accuracy, compared with smear microscopy, in differentiating mtb from other mycobacteria. we aimed to evaluate the reliability and projected impact of naa testing in patients with acid-fast bacilli (afb) smear-positive respiratory samples.201728470022
crystal structure of the essential biotin-dependent carboxylase acca3 from mycobacterium tuberculosis.biotin-dependent acetyl-coa carboxylases catalyze the committed step in type ii fatty acid biosynthesis, the main route for production of membrane phospholipids in bacteria, and are considered a key target for antibacterial drug discovery. here we describe the first structure of acca3, an essential component of the acetyl-coa carboxylase system in mycobacterium tuberculosis (mtb). the structure, sequence comparisons, and modeling of ligand-bound states reveal that the atp cosubstrate-binding sit ...201728469974
a chest wall mass after breast carcinoma surgery: a simple diagnosis?tuberculosis affects pulmonary and extra-pulmonary sites with a multitude of differing presentations. the involvement of thoracic wall is a rare entity. we report the case of a patient who had a tumefaction on the right chest wall 6 months after a right breast mastectomy. after an initial radiological suspicion of malignancy, we detected intraoperatively an abscess in which histologic examination revealed granulomas with multinucleated giant cells.201728469918
construction and analysis of the transcription factor-microrna co-regulatory network response to mycobacterium tuberculosis: a view from the blood.mycobacterium tuberculosis (mtb) infection has been regional outbreak, recently. the traditional focus on the patterns of "reductionism" which was associated with single molecular changes has been unable to meet the demand of early diagnosis and clinical application when current tuberculosis infection happened. in this study, we employed a systems biology approach to collect large microarray data sets including mrnas and micrornas (mirnas) to identify the differentially expressed mrnas and mirna ...201728469803
lineage-specific snps for genotyping of mycobacterium tuberculosis clinical isolates.tuberculosis (tb) is a severe infectious disease worldwide. genetic variation of the causative agent, mycobacterium tuberculosis (mtb), determines the outcomes of infection and anti-tb treatment. until recently, there has been no effective and convenient way for classifying clinical isolates based on the dna sequences of the divergent lineages of mtb infecting human populations. here, we identified single nucleotide polymorphisms (snps) of six representative strains from taiwan by whole-genome s ...201728469152
pyopericardium with cardiac tamponade in a nigerian child with acute osteomyelitis.in pyopericardium, pus accumulates in the pericardial space as a result of infection by pyogenic organisms, most common of which are staphylococcus aureus and mycobacterium tuberculosis. these patients are at risk of cardiac tamponade. apart from pericardiocentesis in the management of these patients, definitive drug treatment may pose a formidable challenge in a setting of coinfection as in patients with tuberculosis who are predisposed to secondary bacterial infections. this was the case of ou ...201728465998
endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron.the iron-regulatory hormone hepcidin is induced early in infection, causing iron sequestration in macrophages and decreased plasma iron; this is proposed to limit the replication of extracellular microbes, but could also promote infection with macrophage-tropic pathogens. the mechanisms by which hepcidin and hypoferremia modulate host defense, and the spectrum of microbes affected, are poorly understood. using mouse models, we show that hepcidin was selectively protective against siderophilic ex ...201728465342
transcription facilitated genome-wide recruitment of topoisomerase i and dna gyrase.movement of the transcription machinery along a template alters dna topology resulting in the accumulation of supercoils in dna. the positive supercoils generated ahead of transcribing rna polymerase (rnap) and the negative supercoils accumulating behind impose severe topological constraints impeding transcription process. previous studies have implied the role of topoisomerases in the removal of torsional stress and the maintenance of template topology but the in vivo interaction of functionall ...201728463980
novel copper(ii) complexes with hydrazides and heterocyclic bases: synthesis, structure and biological studies.five new copper(ii) complexes of the type [cu(no)(nn)(clo4)2], in which no=4-fluorophenoxyacetic acid hydrazide (4-fh) or 4-nitrobenzoic hydrazide (4-nh) and nn=1,10-phenanthroline (phen), 4-4'-dimethoxy-2-2'-bipyridine (dmb) or 2,2-bipyridine (bipy) were synthesized and characterized using various spectroscopic methods. the x-ray structural analysis of one representative compound indicates that the geometry around the copper ion is distorted octahedron, in which the ion is coordinated to hydraz ...201728463762
early detection of the growth of mycobacterium tuberculosis using magnetophoretic immunoassay in liquid culture.tuberculosis (tb) is an often neglected, epidemic disease that remains to be controlled by contemporary techniques of medicine and biotechnology. in this study, a nanoscale sensing system, referred to as magnetophoretic immunoassay (mpi) was designed to capture culture filtrate protein (cfp)-10 antigens effectively using two different types of nanoparticles (nps). two specific monoclonal antibodies against cfp-10 antigen were used, including gold nps for signaling and magnetic particles for sepa ...201728463738
a functional toll-interacting protein variant is associated with bacillus calmette-guérin-specific immune responses and tuberculosis.the molecular mechanisms that regulate tuberculosis susceptibility and bacillus calmette-guérin (bcg)-induced immunity are mostly unknown. however, induction of the adaptive immune response is a critical step in host control of mycobacterium tuberculosis. toll-interacting protein (tollip) is a ubiquitin-binding protein that regulates innate immune responses, including toll-like receptor signaling, which initiate adaptive immunity. tollip variation is associated with susceptibility to tuberculosi ...201728463648
6-nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases.as part of a quest for backups to the antitubercular drug pretomanid (pa-824), we investigated the unexplored 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]-thiazoles and related -oxazoles. the nitroimidazothiazoles were prepared in high yield from 2-bromo-4-nitroimidazole via heating with substituted thiiranes and diisopropylethylamine. equivalent examples of these two structural classes provided broadly comparable mics, with 2-methyl substitution and extended aryloxymethyl side chains preferred; albei ...201728462832
building a full-atom model of l,dtranspeptidase 2 from mycobacterium tuberculosis for screening new inhibitors.l,d-transpeptidase 2 from mycobacterium tuberculosis plays a key role in the formation of the cell wall of a pathogen and catalyzes the cross-linking of growing peptidoglycan chains by non-classical 3-3 bonds, which causes resistance to a broad spectrum of penicillins. molecular modeling of enzyme interactions with the n- and c-terminal tetrapeptide fragments of growing peptidoglycan chains has been performed for the first time and has allowed us to highlight the peculiarities of their binding a ...201728461973
proteomics for the investigation of mycobacteria.the physiology of mycobacterium tuberculosis, the causative agent of tuberculosis, is being studied with intensity. however, despite the genomic and transcriptomic data available today, the pathogenic potential of these bacteria remains poorly understood. therefore, proteomic approaches seem relevant in studying mycobacteria. this review covers the main stages in the proteomic analysis methods used to study mycobacteria. the main achievements in the area of m. tuberculosis proteomics are describ ...201728461970
effect of tuberculosis treatment on leptin levels, weight gain, and percentage body fat in indonesian children.tuberculosis (tb) remains a problem in the community. tb patients usually experience malnutrition, which is characterized by both decreased body weight (bw) and body fat percentage (bfp). leptin, an important regulator of bw, also plays an important role in cellular immunity, which is integral to defense against mycobacterium tuberculosis infection. we analyzed the effect of an anti-tb treatment regimen on the leptin level, bw, and bfp of children with tb.201728461825
modulation of mycobacterium tuberculosis-specific humoral immune responses is associated with strongyloides stercoralis co-infection.helminth infections are known to influence t cell responses in latent tuberculosis (ltbi). whether helminth infections also modulate b cell responses in helminth-tuberculosis co-infection is not known.201728459817
peripancreatic tuberculous lymphadenitis diagnosed via endoscopic ultrasound-guided fine-needle aspiration and polymerase chain reaction.we performed endoscopic ultrasound-guided fine-needle aspiration (eus-fna) on a patient presenting with an asymptomatic peripancreatic mass-like lesion. the aspiration cytologic finding was class ii. on positron emission tomography-computed tomography (pet-ct), there were hot spots in the left supra-clavicular lymph node and the peripancreatic lesion. a whole biopsy of the left supra-clavicular lymph node revealed tuberculous lymphadenitis. polymerase chain reaction (pcr) using tissue obtained v ...201728458310
targeting isocitrate lyase for the treatment of latent tuberculosis.tuberculosis (tb) is an infectious disease caused by mycobacterium tuberculosis that can remain dormant for many years before becoming active. one way to control and eliminate tb is the identification and treatment of latent tb, preventing infected individuals from developing active tb and thus eliminating the subsequent spread of the disease. isocitrate lyase (icl) is involved in the mycobacterial glyoxylate and methylisocitrate cycles. icl is important for the growth and survival of m. tubercu ...201728458043
mycobacterium tuberculosis infection at pacemaker implantation site.expanding clinical indications of cardiac rhythm management have led to an increased use of pacemaker implantation which is associated with increased incidence of pacemaker infections. staphylococcus aureus and epidermidis account for the majority of pacemaker infections. infection of implantable cardiac devices by mycobacterium species, particularly mycobacterial tuberculosis is rare. we present a case of delayed pacemaker pocket infection with tuberculosis and review of literature of pacemaker ...201728457043
qsar based therapeutic management of m. tuberculosis.mycobacterium tuberculosis is responsible for severe mortality and morbidity worldwide but, under-developed and developing countries are more prone to infection. in search of effective and wide-spectrum anti-tubercular agents, interdisciplinary approaches are being explored. of the several approaches used, computer based quantitative structure activity relationship (qsar) have gained momentum. structure-based drug design and discovery implies a combined knowledge of accurate prediction of ligand ...201728456911
positive epistasis of major low-cost drug resistance mutations rpob531-ttg and katg315-acc depends on the phylogenetic background of mycobacterium tuberculosis strains.mycobacterium tuberculosis beijing genotype strains increasingly circulate in different world regions, either as historical endemic, e.g. in east asia, or recently imported, e.g. in south america, and this family is regarded as the most successful lineage of the global tuberculosis (tb) epidemic. here we analysed the transmission capacity of these strains in the context of their phylogenetic background and drug resistance mutations. the study collection included all multidrug resistant (mdr) str ...201728456705
selection and identification of specific glycoproteins and glycan biomarkers of macrophages involved in mycobacterium tuberculosis infection.macrophages are the primary host target cells of mycobacterium tuberculosis (m.tb). however, little is known about the changes of membrane glycopatterns of macrophages in response to m. tb infection. using lectin microarrays we compared the differential expression of glycopatterns of macrophages upon stimulation with the heat-inactivated virulent m.tb h37rv or attenuate m.tb h37ra. we found that widespread alteration of macrophage membrane glycopatterns were induced by the heat-inactivated virul ...201728454656
the diacylglycerol acyltransferase rv3371 of mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations.triacylglycerol (tag) is important to mycobacteria both as cell envelope component and energy reservoir. mycobacterium tuberculosis (mtb) genome encodes at least 15 putative tag synthase (tgs)s. we report that one of these genes, rv3371, specific to pathogenic mycobacteria, when expressed in m. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated tag levels. rv3371 was found to largely localize in the cell membrane. the rv3371 promot ...201728454654
strains of mycobacterium tuberculosis transmitting infection in brazilian households and those associated with community transmission of tuberculosis.molecular epidemiologic studies have shown that the dynamics of tuberculosis transmission varies geographically. we sought to determine which strains of mycobacterium tuberculosis (mtb) were infecting household contacts (hhc), and which were causing clusters of tuberculosis (tb) disease in vitoria-es, brazil. a total of 741 households contacts (445 tst +) and 139 index cases were characterized according to the proportion of contacts in each household that had a tuberculin skin test positive: low ...201728454653
selection, characterization, and application of dna aptamers for detection of mycobacterium tuberculosis secreted protein mpt64.rapid detection of mycobacterium tuberculosis (mtb), an etiological agent of tuberculosis (tb), is important for global control of this disease. aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. the aim of the current study was to select and characterize single-stranded dna aptamers against mpt64 protein, one of the predominant secreted proteins of mtb pathogen. aptamers specific to mpt64 protein were sele ...201728454652
clinical evaluation of the abbott realtime mtb assay for direct detection of mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.rapid and reliable diagnosis is crucial for correct management of tuberculosis. the abbott realtime mtb assay represents a novel qualitative real-time pcr assay for direct detection of m. tuberculosis-complex (mtb) dna from respiratory samples. the test targets two highly conserved sequences, the multi-copy insertion element is6110 and the protein antigen b (pab) gene of mtb, allowing even the detection of is6610-deficient strains. we evaluated this commercial diagnostic test by analyzing 200 re ...201728454651
the siglec14 null allele is associated with mycobacterium tuberculosis- and bcg-induced clinical and immunologic outcomes.humans exposed to mycobacterium tuberculosis (mtb) have variable susceptibility to tuberculosis (tb) and its outcomes. siglec-5 and siglec-14 are members of the sialic-acid binding lectin family that regulate immune responses to pathogens through inhibitory (siglec-5) and activating (siglec-14) domains. the siglec14 coding sequence is deleted in a high proportion of individuals, placing a siglec5-like gene under the expression of the siglec14 promoter (the siglec14 null allele) and causing expre ...201728454648
activity of rifampicin and linezolid combination in mycobacterium tuberculosis.linezolid (lzd) is not commonly used for treating tuberculosis (tb), but in some patients with drug-resistant tb it is being used. however, the in vitro lzd activity, in combination with rifampicin (rif) against mycobacterium tuberculosis has not been fully elucidated.201728454646
revisiting the hunter gaston discriminatory index: note of caution and courses of change.hunter gaston discriminatory index (hgdi) is a widely used estimator of discriminatory power of genotyping methods and diversity of molecular markers in bacterial pathogens, including mycobacterium tuberculosis. in my opinion, the index is somewhat misleading: a closer look at common practice and particular studies reveals that values in the range of 0.6-0.9 are modest but uncritically perceived as high. i propose and discuss three courses of change: (i) to continue using hgdi but be aware of th ...201728454645
genetic diversity of immune-related antigens in region of difference 2 of mycobacterium tuberculosis strains.region of difference 2 (rd2) was lost during the ongoing propagation of bcg between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. some data demonstrate that rd2 plays a role in mycobacterial virulence, and that its deletion from mycobacterium tuberculosis leads to a decrease in bacterial growth in both a macrophage and a murine model. human t-cell epitopes of m. tuberculosis are evolutionarily hyperconserved and thus it was deduced that m. tuberculo ...201728454644
multi-subunit bcg booster vaccine gamtbvac: assessment of immunogenicity and protective efficacy in murine and guinea pig tb models.new innovative vaccines are highly needed to combat the global threat posed by tuberculosis. efficient components-antigens and adjuvants-are crucial for development of modern recombinant tb vaccines. this study describes a new vaccine (gamtbvac) consisting of two mycobacterial antigen fusions (ag85a and esat6-cfp10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of deae-dextran core, and with cpg oligodeoxynucleotides (tlr9 agonists). gamtbvac and its co ...201728453555
expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors.the global incidence of tuberculosis is increasing at an alarming rate, and mycobacterium tuberculosis (mtb) is the causative agent for tuberculosis, a disease with high mortality. lipoarabinomannan (lam) is one of the major components of the mtb cellular envelope and is an attractive scaffold for developing anti-tubercular drugs, vaccines and diagnostics. herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time. the arabinomannan synthe ...201728451321
fundus findings in a series of patients with extrapulmonary tuberculosis in thailand.the aim of this study was to determine the frequency of fundus abnormalities among patients who are undergoing or have recently completed treatment for extrapulmonary tuberculosis (etb).201728450377
system for efficacy and cytotoxicity screening of inhibitors targeting intracellular mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis (tb), is a leading cause of morbidity and mortality worldwide. with the increased spread of multi drug-resistant tb (mdr-tb), there is a real urgency to develop new therapeutic strategies against m. tuberculosis infections. traditionally, compounds are evaluated based on their antibacterial activity under in vitro growth conditions in broth; however, results are often misleading for intracellular pathogens like m. tuberculosis since ...201728448028
mitigation of discordant rifampicin-susceptibility results obtained by xpert mycobacterium tuberculosis/rifampicin and mycobacterium growth indicator tube.simultaneous use of genotypic and phenotypic diagnostic tools for detection of rifampicin (rif) susceptibility may yield discrepant results.201728447869
mtbvac from discovery to clinical trials in tuberculosis-endemic countries.bcg remains the only vaccine against tuberculosis (tb) in use today and despite its impressive global coverage, the nature of bcg protection against the pulmonary forms of tb remains subject to ongoing debate. because of the limitations of bcg, novel tb vaccine candidates have been developed and several have reached the clinical pipeline. one of these candidates is mtbvac, the first and only tb vaccine in the clinical pipeline to date based on live-attenuated mycobacterium tuberculosis that has ...201728447476
structural investigations on orotate phosphoribosyltransferase from mycobacterium tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis.the mycobacterium tuberculosis orotate phosphoribosyltransferase (mtoprt) catalyses the conversion of α-d-5-phosphoribosyl-1-pyrophosphate (prpp) and orotate (oa) in pyrophosphate and orotidine 5'-monophosphate (omp), in presence of mg(2+). this enzyme is the only responsible for the synthesis of orotidine 5'-monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway, making mtoprt an attractive drug target for the development of antitubercular agents. we report the crystal st ...201728446777
use of genexpert remnants for drug resistance profiling and molecular epidemiology of tuberculosis in libreville, gabon.multidrug-resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis pose major problems for global health. the genexpert mtb/rif (xpert) assay rapidly detects resistance to rifampin (rif(r)), but for detection of the additional resistance that defines mdr-tb (mdr tuberculosis) and xdr-tb, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. we sought to determine whether the remnants of sputa prepared for the xper ...201728446574
distinct prevalence of drug-resistant tuberculosis in gansu, china: a retrospective study on drug susceptibility profiles between 2010 and 2014.limited knowledge is available on regional distribution of antituberculosis (tb) drug resistance and on province-specific time-trends in tb drug susceptibility in china. to obtain the latest information about the dynamics of drug-resistant tb in gansu province, we conducted a retrospective study and analyzed data on drug resistance among new tb cases diagnosed between june 2010 and may 2014 in gansu, china. the data were collected from the only tb surveillance and treatment hospital in gansu and ...201728445109
current approaches and future prospects of nanomedicines in tuberculosis therapy.tuberculosis (tb), which is caused by the mycobacterium tuberculosis, is a serious threat and one of the major health problems worldwide. in recent years, an estimated of 9.6 million tb cases occurred and 1.5 million death occurred due to tb worldwide. the present review is an attempt to introduce this disease focusing on the pathophysiology of the disease, the current approachesand the related patents for treatment and the future planningfor combating this disease.201728443511
evaluation of a new ifn-γ release assay for rapid diagnosis of active tuberculosis in a high-incidence setting.blood-based interferon-gamma (ifn-γ) release assays (igras) have been proven to be useful in the diagnosis of mycobacterium tuberculosis (mtb) infection. however, igras have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. the established t-spot. tb assay containing mtb-specific antigens esat-6 and cfp10 are widely used for immunodiagonsis of mtb infection, but the high cost is one of the restricting ...201728443247
estimating tuberculin skin test reactions among children and teenagers who received the bacillus calmette-guerin vaccination at birth: a meta-analysis.tuberculin skin reaction size is one indicator of bacillus calmette-guérin (bcg) vaccine efficacy and a way to diagnose latent infection. several primary studies have examined this issue. combining the results of these studies using a meta-analysis will provide reliable evidence regarding this indicator for policymakers. this study aimed to estimate the total frequency of different tuberculin skin test reactions among iranian children and teenagers who received the bcg vaccination at birth.201728443219
the exit strategy: an approach for identifying bacterial proteins exported during host infection.exported proteins of bacterial pathogens function both in essential physiological processes and in virulence. past efforts to identify exported proteins were limited by the use of bacteria growing under laboratory (in vitro) conditions. thus, exported proteins that are exported only or preferentially in the context of infection may be overlooked. to solve this problem, we developed a genome-wide method, named exit (exported in vivotechnology), to identify proteins that are exported by bacteria d ...201728442606
complex multifractal nature in mycobacterium tuberculosis genome.the mutifractal and long range correlation (c(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. in this study c(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria mycobacterium tuberculosis. genomic sequences of m. tuberculosis isolates displayed significant variations in c(r) and f(α) reflecting inherent differences in sequences among iso ...201728440326
latently and uninfected healthcare workers exposed to tb make protective antibodies against mycobacterium tuberculosis.the role of igs in natural protection against infection by mycobacterium tuberculosis (mtb), the causative agent of tb, is controversial. although passive immunization with mabs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in b cell-depleted animals only showed modest phenotypes. we do not know if humans make protective antibody responses. here, we investigated whether healthcare workers in a beijing tb hospital-who, although expos ...201728438994
pyrazinoic acid inhibits a bifunctional enzyme in mycobacterium tuberculosis.pyrazinamide (pza), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. while the mechanism of activation of this prodrug into pyrazinoic acid (poa) by mycobacterium tuberculosis has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. here, we report how a new pza resistance determinant, the asp67asn substitution in rv2783, confers m. tuberculosis resistance to pza. expression of th ...201728438933
effects on the qt interval of a gatifloxacin-containing regimen versus standard treatment of pulmonary tuberculosis.the effects on ventricular repolarization-recorded on the electrocardiogram (ecg) as lengthening of the qt interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. a correction factor (qtc) is introduced to make the qt independent of the heart rate, translating into the slope of the regression line between qt and heart rate being close to zero. ecgs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) ...201728438924
convenient pcr method for variable-number tandem-repeat typing of mycobacterium tuberculosis clinical isolates.variable-number tandem-repeat typing for mycobacterium tuberculosis clinical isolates contributes to evidence-based tuberculosis control. however, cumbersome pcr procedures for the typing have disturbed routine analyses. we proposed a convenient pcr method for the typing using a pcr master mix that provides rapidity and long-term stability of the frozen pcr cocktail.201728438643
isolated splenic tuberculosis with subsequent paradoxical deterioration: a case report.isolated tuberculosis of the spleen has been described occasionally in literature, mostly in immunosuppressed individuals with various risk factors. sequestration in the spleen makes such mycobacterium tuberculosis infection difficult to diagnose. this report describes an extremely rare case of isolated splenic tuberculosis in an immunocompetent individual.201728438221
early detection of multidrug- and pre-extensively drug-resistant tuberculosis from smear-positive sputum by direct sequencing.emergence of multidrug- and extensively drug-resistant tuberculosis (m/xdr-tb) is a major hurdle for tb control programs especially in developing countries like china. resistance to fluoroquinolones is high among mdr-tb patients. early diagnosis of mdr/pre-xdr-tb is essential for lowering transmission of drug-resistant tb and adjusting the treatment regimen.201728438132
reproducibility of african giant pouched rats detecting mycobacterium tuberculosis.african pouched rats sniffing sputum samples provided by local clinics have significantly increased tuberculosis case findings in tanzania and mozambique. the objective of this study was to determine the reproducibility of rat results.201728438117
an attenuated mycobacterium tuberculosis clinical strain with a defect in esx-1 secretion induces minimal host immune responses and pathology.although mycobacterium tuberculosis (m.tb) dk9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (h56) induced poor protection against it. both attenuation and lack of protection are because m.tb dk9897 cannot secrete the esxa virulence factor nor induce a host response against it. genome sequencing identified a frameshift mutation in the eccca1 gene. since the encoded eccca1 protein provides energy for esx-1 secret ...201728436493
functional, thermodynamics, structural and biological studies of in silico-identified inhibitors of mycobacterium tuberculosis enoyl-acp(coa) reductase enzyme.novel chemotherapeutics agents are needed to kill mycobacterium tuberculosis, the main causative agent of tuberculosis (tb). the m. tuberculosis 2-trans-enoyl-acp(coa) reductase enzyme (mtinha) is the druggable bona fide target of isoniazid. new chemotypes were previously identified by two in silico approaches as potential ligands to mtinha. the inhibition mode was determined by steady-state kinetics for seven compounds that inhibited mtinha activity. dissociation constant values at different te ...201728436453
il-10 down-regulates the expression of survival associated gene hspx of mycobacterium tuberculosis in murine macrophage.mycobacterium tuberculosis (mtb) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. amongst the many known factors, small heat shock protein 16.3 (shsp16.3) of mtb encoded by gene hspx has been reported to be critical for the survival of mtb. in the present study, the effect of recombinant murine interferon-gamma (rmifn-γ) and recombinant murine interleukin-10 (rmil-10) on the expression of gene hspx of mtb in murine macrophage raw264.7 has been invest ...201728435012
defining a research agenda to address the converging epidemics of tuberculosis and diabetes: part 2: underlying biologic mechanisms.there is growing interest in the re-emerging interaction between type 2 diabetes (dm) and tb, but the underlying biologic mechanisms are poorly understood despite their possible implications in clinical management. experts in epidemiologic, public health, basic science, and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-occurrence of tb and dm. we identified gaps in current knowledge of altered immunity in patients with ...201728434937
distant phe345 mutation compromises the stability and activity of mycobacterium tuberculosis isocitrate lyase by modulating its structural flexibility.isocitrate lyase (icl), a potential anti-tubercular drug target, catalyzes the first step of the glyoxylate shunt. in the present investigation, we studied the conformational flexibility of mtbicl to better understand its stability and catalytic activity. our biochemical results showed that a point mutation at phe345, which is topologically distant (>10 å) to the active site signature sequence ((189)kkcgh(193)), completely abolishes the activity of the enzyme. in depth computational analyses wer ...201728432345
mycobacterium tuberculosis lineage distribution in xinjiang and gansu provinces, china.mycobacterium tuberculosis (m. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (tb). in this study, 187 m. tuberculosis isolates from xinjiang uygur autonomous region (xinjiang) and gansu province in china were genotyped using large sequence polymorphisms (lsps) and variable number tandem repeats (vntr). ten isolates, which represent major nodes of vntr-based minimum spanning tree, were selected and subsequently subjected to multi-locus se ...201728432321
suppressors of cytokine signaling in tuberculosis.tuberculosis (tb), a global disease mainly infected by mycobacterium tuberculosis, remains leading public health problem worldwide. suppressors of cytokine signaling (socss) play important roles in the protection against microbial infection. however, the relationship between members of the socs family and tuberculosis infection remains unclear. using peripheral blood mononuclear cells, we investigated the mrna expression profiles of socs subfamilies among active tb, latent tuberculosis infection ...201728430824
diagnosis of smear-negative tuberculosis is greatly improved by xpert mtb/rif.diagnosis of pulmonary (ptb) and extra-pulmonary tuberculosis (eptb) in smear-negative patients can be difficult. we assessed retrospectively the performance of xpert mtb/rif system (xpert, cepheid) in diagnosing smear-negative tuberculosis (tb), which represents the most common form of tb in a low incidence setting.201728430807
bedaquiline susceptibility test for totally drug-resistant tuberculosis mycobacterium tuberculosis.this study aimed to provide information that bedaquilline is significantly effective for treatment of totally drug resistant (tdr) mycobacterium tuberculosis that shows resistant to all first- and second-line drugs-using an innovative disc agarose channel (dac) system. time-lapse images of single bacterial cells under culture conditions with different concentrations of bedaquiline were analysed by image processing software to determine minimum inhibitory concentrations (mics). bedaquiline inhibi ...201728429168
dihydrolipoamide dehydrogenase-lpd (rv0462)-specific t cell recall responses are higher in healthy household contacts of tb: a novel immunodominant antigen from m. tuberculosis.the partial effectiveness against pulmonary tuberculosis (ptb), displayed by the existing tuberculosis (tb) vaccine, bacillus calmette-guérin (bcg), highlights the need for novel vaccines to replace or improve bcg. in tb immunology, antigen-specific cellular immune response is frequently considered indispensable. latency-associated antigens are intriguing as targets for tb vaccine development. the mycobacterial protein, dihydrolipoamide dehydrogenase (lpd; rv0462), the third enzyme of the pyruva ...201728428201
novel and revisited approaches in antituberculosis drug discovery.the increasing prevalence of multidrug-resistant mycobacterium tuberculosis (mtb) necessitates the discovery and development of novel drugs against tuberculosis. in this review, we focus on two recent approaches that led to the discovery of promising antitubercular compound classes: (i) hits derived from large compound library screens are increasingly difficult to translate into clinical application; this in turn fostered the development of innovative screening methods. (ii) an alternative strat ...201728427007
rapid detection of mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using xpert mtb/rif.tuberculosis (tb) is a serious public health problem in developing countries such as pakistan. rapid diagnosis of tb and detection of drug resistance are very important for timely and appropriate management of multidrug-resistant tb (mdr-tb).201728425873
mycobacterium tuberculosis resistance prediction and lineage classification from genome sequencing: comparison of automated analysis tools.whole-genome sequencing (wgs) has the potential to accelerate drug-susceptibility testing (dst) to design appropriate regimens for drug-resistant tuberculosis (tb). several recently developed automated software tools promise to standardize the analysis and interpretation of wgs data. we assessed five tools (castb, kvarq, mykrobe predictor tb, phyresse, and tbprofiler) with regards to dst and phylogenetic lineage classification, which we compared with phenotypic dst, sanger sequencing, and tradit ...201728425484
data intensive genome level analysis for identifying novel, non-toxic drug targets for multi drug resistant mycobacterium tuberculosis.we report the construction of a novel systems biology based virtual drug discovery model for the prediction of non-toxic metabolic targets in mycobacterium tuberculosis (mtb). this is based on a data-intensive genome level analysis and the principle of conservation of the evolutionarily important genes. in the 1623 sequenced mtb strains, 890 metabolic genes identified through a systems approach in mtb were evaluated for non-synonymous mutations. the 33 genes showed none or one variation in the e ...201728425478
interactions between type 1 interferons and the th17 response in tuberculosis: lessons learned from autoimmune diseases.the classical paradigm of tuberculosis (tb) immunity, with a central protective role for th1 responses and ifn-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing th1 immunity. moreover, preclinical tb models have shown that increasing ifn-γ responses in the lungs is more damaging to the host than to the pathogen. type 1 interferon signaling and altered th17 responses have also been associated with active tb, but their functiona ...201728424682
the within-host population dynamics of mycobacterium tuberculosis vary with treatment efficacy.combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. the mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. we address this question by studying the population dynamics of mycobacterium tuberculosis ...201728424085
erratum to: rhodococcus erythropolis as a host for expression, secretion and glycosylation of mycobacterium tuberculosis proteins. 201728424079
zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase streptomyces coelicolor glgei-v279s.we synthesized and evaluated new zwitterionic inhibitors against glycoside hydrolase-like phosphorylase streptomyces coelicolor (sco) glgei-v279s which plays a role in α-glucan biosynthesis. sco glgei-v279s serves as a model enzyme for validated anti-tuberculosis (tb) target mycobacterium tuberculosis (mtb) glge. pyrrolidine inhibitors 5 and 6 were designed based on transition state considerations and incorporate a phosphonate on the pyrrolidine moiety to expand the interaction network between t ...201728422240
accurate and effective multidrug-resistant mycobacterium tuberculosis detection method using gap-filling ligation coupled with high-resolution capillary electrophoresis-based single strand conformation polymorphism.tuberculosis (tb) has severely threatened public health via emerging multidrug-resistant (mdr) and extensively drug-resistant (xdr) mycobacterium tuberculosis (mtb) strains. for effective tb treatment, rapid, accurate, and multiplex detection of drug resistance is extremely important. however, conventional methods for tb diagnosis are time consuming and have a limited effect on treatment. nucleic acid-based molecular detection methods have been developed as an effective mdr/xdr-tb diagnosis tech ...201728422112
high detection rates of urine mycobacterium tuberculosis in patients with suspected miliary tuberculosis.objective the utility of detecting mycobacterium tuberculosis in urine samples from patients with pulmonary tuberculous with diffuse small nodular shadows (suspected miliary tuberculosis (mtb)) is still unclear in japan. a retrospective cross-sectional study was conducted to investigate the detection rates of m. tuberculosis in urine of patients with suspected mtb. methods among 687 hospitalized patients with tuberculosis, 45 with culture-confirmed suspected mtb and the data of culture and polym ...201728420836
antibacterial, antifungal and antimycobacterial compounds from cyanobacteria.infections from multidrug resistant (mdr) pathogenic bacteria, fungi and mycobacterium tuberculosis remain progressively intractable. the search of effective antimicrobials from other possible non-conventional sources against mdr pathogenic bacteria, fungi and mycobacteria is call of the day. this review considers 121 cyanobacterial compounds or cyano-compounds with antimicrobial activities. chemical structures of cyano-compounds were retrieved from chemspider and pubchem databases and were visu ...201728419973
mycobacterium tuberculosis proteasomal atpase mpa has a β-grasp domain that hinders docking with the proteasome core protease.mycobacterium tuberculosis (mtb) has a proteasome system that is essential for its ability to cause lethal infections in mice. a key component of the system is the proteasomal adenosine triphosphatase (atpase) mpa, which captures, unfolds, and translocates protein substrates into the mtb proteasome core particle for degradation. here, we report the crystal structures of near full-length hexameric mtb mpa in apo and adp-bound forms. surprisingly, the structures revealed a ubiquitin-like β-grasp d ...201728419599
activation of tlr7 inhibition of mycobacterium tuberculosis survival by autophagy in raw 264.7 macrophages.the aim of the study was to evaluate the effect of regulation of tlr7 on mycobacterium tuberculosis (mtb) survival in macrophages. tlr7 expression in macrophages infected by mtb was detected by rt-pcr and western blotting. regulation of tlr7 was achieved by single strand rna (ssrna) or sirna. the effects of tlr7 on mtb survival and cell viability were detected by acid fast staining and cell counting kit-8, respectively. cell ultrastructure was observed via transmission electron microscopy (tem), ...201728419514
mutations in streptomycin resistance genes and their relationship to streptomycin resistance and lineage of mycobacterium tuberculosis thai isolates.streptomycin (sm) is recommended by the world health organization (who) as a part of standard regimens for retreating multidrug-resistant tuberculosis (mdr-tb) cases. the incidence of mdr-tb in retreatment cases was 19% in thailand. to date, information on sm resistance (smr) gene mutations correlated to the smr of mycobacterium tuberculosis thai isolates is limited. in this study, the mutations in rpsl, rrs, gidb, and whib7 were investigated and their association to smr and the lineage of m. tu ...201728416956
efflux attenuates the antibacterial activity of q203 in mycobacterium tuberculosis.new and improved treatments for tuberculosis (tb) are urgently needed. recently, it has been demonstrated that verapamil, an efflux inhibitor, can reduce bacterial drug tolerance caused by efflux pump activity when administered in combination with available antituberculosis agents. the aim of this study was to evaluate the effectiveness of verapamil in combination with the antituberculosis drug candidate q203, which has recently been developed and is currently under clinical trials as a potentia ...201728416541
inhibition of the pi3k-akt-mtor signaling pathway in t lymphocytes in patients with active tuberculosis.to investigate pi3k-akt-mtor signaling pathway changes and the proliferation of foxp3(+)treg cells in patients with active tuberculosis.201728416440
structural analysis of the interaction between spiroisoxazoline smart-420 and the mycobacterium tuberculosis repressor ethr2.inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. one example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor ethr. recently, we discovered that inhibition of a second transcriptional repressor, ethr2, leads to the awakening of a new ethionamide bio-activ ...201728416386
smrt genome assembly corrects reference errors, resolving the genetic basis of virulence in mycobacterium tuberculosis.the genetic basis of virulence in mycobacterium tuberculosis has been investigated through genome comparisons of virulent (h37rv) and attenuated (h37ra) sister strains. such analysis, however, relies heavily on the accuracy of the sequences. while the h37rv reference genome has had several corrections to date, that of h37ra is unmodified since its original publication.201728415976
antitubercular activity of zno nanoparticles prepared by solution combustion synthesis using lemon juice as bio-fuel.in this study, we report the synthesis, structural and morphological characteristics of zinc oxide (zno) nanoparticles using solution combustion synthesis method where lemon juice was used as the fuel. in vitro anti-tubercular activity of the synthesized zno nanoparticles and their biocompatibility studies, both in vitro and in vivo were carried out. the synthesized nanoparticles showed inhibition of mycobacterium tuberculosis h37ra strain at concentrations as low as 12.5μg/ml. in vitro cytotoxi ...201728415385
fullerene-doped polyaniline as new redox nanoprobe and catalyst in electrochemical aptasensor for ultrasensitive detection of mycobacterium tuberculosis mpt64 antigen in human serum.tuberculosis caused by mycobacterium tuberculosis (mtb) is still a major threat to global public health. however, the existing methods for mtb detection are usually complicated and time consuming with unsatisfactory sensitivity and specificity. in this work, a relatively simple and ultrasensitive electrochemical aptasensor based on novel signal generation and amplification was constructed for the determination of mtb antigen mpt64. the coil-like fullerene (c60)-doped polyaniline (c60-pan) nanohy ...201728414975
transcriptional networks are associated with resistance to mycobacterium tuberculosis infection.understanding mechanisms of resistance to m. tuberculosis (m.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases, such as hiv.201728414762
a m. avium complex spondylodiscitis in a middle-aged woman with diabetes.spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral disk space, is the reason for low back pain in a minority of cases. this is caused by various pathogens. mycobacterium tuberculosis is responsible for 17-39% of all the cases of spondylodiscitis. on the contrast, spondylodiscitis from non tuberculous mycobacteria is extremely rare in literature. we describe a 68 -year old diabetic woman which is the first case of bone marrow involvement by m. intracellulare (member ...201728413773
investigation of omnigene·sputum performance in delayed tuberculosis testing by smear, culture, and xpert mtb/rif assays in uganda.omnigene·sputum (om-s) is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. om-s-treated sputum samples were assayed in several tests after multiday holds. raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the om-s group [om-s added at collection (no other processing required) and tested after 0- to 5-day holds at room temperature] or standard-of-care (soc) group (naoh/n-acetyl ...201728413105
structural basis for ribosome protein s1 interaction with rna in trans-translation of mycobacterium tuberculosis.ribosomal protein s1 (rpsa), the largest 30s protein in ribosome, plays a significant role in translation and trans-translation. in mycobacterium tuberculosis, the c-terminus of rpsa is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between mtrpsa and tmrna in trans-translation. however, the molecular mechanism underlying the interaction of mtrpsa with tmrna remains unknown. we herein analyzed the interaction of the c-terminal domain of mtrpsa with three rna ...201728412369
the immunosuppressive effects of a novel recombinant lipq (rv2485c) protein of mycobacterium tuberculosis on human macrophage cell lines.mycobacterium tuberculosis (mtb), an intracellular pathogen, still represents a major global health challenge. a number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of mycobacterium tubercu ...201728412202
qsar, docking studies of 1,3-thiazinan-3-yl isonicotinamide derivatives for antitubercular activity.the enzyme - enoyl acyl carrier protein reductase (enoyl acp reductase) is a validated target for antitubercular activity. inhibition of this enzyme interferes with mycolic acid synthesis which is crucial for mycobacterium tuberculosis cell growth. in the present work 2d and 3d quantitative structure activity relationship (qsar) studies were carried out on a series of thiazinan-isoniazid pharmacophore to design newer analogues. for 2d qsar, the best statistical model was generated using sa-mlr m ...201728411471
synthesis and immunogenicity of pg-tb1 monovalent glycoconjugate.a pg-tb1 hapten from the west beijing strains of mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to crm197 in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent t-dependent conjugate vaccine. the intermediate monoester can be easily purified and the degree of incorporation can be monitored by maldi-tof mass spectrometry. after administered systemically in mice without any adjuvant ...201728411454
detection of pyrazinamide resistance of mycobacterium tuberculosis using nicotinamide as a surrogate.despite the importance of pyrazinamide (pza) in tuberculosis treatment, pza susceptibility testing is not routinely performed because of its acid ph requirement. we evaluated the microplate alamar blue assay (maba) to detect resistance to pza using nicotinamide (nic) as a surrogate in neutral ph and identify the appropriate cutoff point for the assay.201728411185
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