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critical role of trif and myd88 in mycobacterium tuberculosis hsp70-mediated activation of dendritic cells.as a potent immune regulator, heat shock protein 70 derived from mycobacterium tuberculosis (mtb hsp70) has adjuvant effect and activates immune cells such as macrophages and dendritic cells (dcs). although toll-like receptors (tlrs) are known to involve in dcs activation by mtb hsp70, there is still a controversy and the underlying mechanism is not well understood. in this study, we examined whether trif and myd88, the core adaptor molecules for tlrs signaling, regulate mtb hsp70-induced dcs ac ...201525461391
the development of "fab-chips" as low-cost, sensitive surface-enhanced raman spectroscopy (sers) substrates for analytical applications.the demand for methods and technologies capable of rapid, inexpensive and continuous monitoring of health status or exposure to environmental pollutants persists. in this work, the development of novel surface-enhanced raman spectroscopy (sers) substrates from metal-coated silk fabric, known as zari, presents the potential for sers substrates to be incorporated into clothing and other textiles for the routine monitoring of important analytes, such as disease biomarkers or environmental pollutant ...201525460852
drug resistance characteristics of mycobacterium tuberculosis isolates to four first-line antituberculous drugs from tuberculosis patients with aids in beijing, china.the objective of this study was to investigate the drug resistance characteristics of mycobacterium tuberculosis isolates to four first-line antituberculous drugs (atds) from tuberculosis (tb) patients with aids in beijing, china. all m. tuberculosis strains were isolated from specimens from tb patients with aids hospitalised between april 2010 and october 2012. isolates were cultured by mycobacterial culture methods and were identified by multilocus pcr. drug sensitivity testing was performed b ...201525459740
in vitro synergistic activity of clofazimine and other antituberculous drugs against multidrug-resistant mycobacterium tuberculosis isolates.clofazimine (clo) is a promising candidate drug for use in the management of multidrug-resistant tuberculosis (mdr-tb) patients. in this study, the minimum inhibitory concentration (mic) method was used to investigate drug susceptibility to clo as well as potential synergies between clo and other antituberculous drugs, including ethambutol (emb), levofloxacin (lev), moxifloxacin (mox), amikacin (amk) and capreomycin (cap), among mdr-tb isolates from china. a total of 195 mdr-tb isolates were col ...201525459737
molecular characterisation of extensively drug-resistant mycobacterium tuberculosis isolates in china.the emergence of extensively drug-resistant tuberculosis (xdr-tb) in china is a great threat to tb control. to determine the molecular characterisation of xdr-tb isolates from china and the correlations between specific drug resistance-associated mutations and different genotype strains, 58 xdr-tb isolates were sequenced in eight drug loci, including katg, inha, oxyr-ahpc intergenic region, rpob, eis, rrs, gyra and gyrb, and were genotyped using spoligotyping and analysis of the noise transfer f ...201525465521
synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives.new anti-tubercular agents, imidazo[1,2-a]pyridine-2-carboxamide derivatives (5a-q) have been designed and synthesized. the structural considerations of the designed molecules were further supported by the docking study with a long-chain enoyl-acyl carrier protein reductase (inha). the chemical structures of the new compounds were characterized by ir, (1)h nmr, (13)c nmr, hrms and elemental analysis. in addition, single crystal x-ray diffraction has also been recorded for compound 5f. compounds ...201525462270
antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of mycobacterium tuberculosis.various classes of natural products and synthetic compounds were tested against reference strains and clinical multidrug resistant isolates of mycobacterium tuberculosis. vermelhotin (19), a natural tetramic acid from fungi, was the most active toward clinical mdr tb isolates (mic 1.5-12.5 μg/ml). synthetic compounds (i.e. benzoxazocines, coumarins, chromenes, and pyrrolodiquinoline derivatives) were prepared by green chemistry approaches. under microwave irradiation, a one-pot synthesis of pyrr ...201525462220
diversity and disease pathogenesis in mycobacterium tuberculosis.the increasing availability of whole-genome sequence (wgs) data for mycobacterium tuberculosis, the bacterium that causes tuberculosis (tb), suggests that circulating genotypes have been molded by three dominant evolutionary forces: long-term persistence within the human population, which requires a core programme of infection, disease, and transmission; selective pressure on specific genomic loci, which provides evidence of lineage-specific adaptation to host populations; and drug exposure, whi ...201525468790
phenotypic characterization of a novel double knockout pkni/dacb2 from mycobacterium tuberculosis.serine/threonine protein kinases play a major role in peptidoglycan biosynthesis in mycobacterium tuberculosis. to explore the mechanism in detail, in the present study, we have constructed a double knockout (dko) strain lacking pkni and dacb2 in m. tuberculosis. initially, we analyzed the colony morphology and found that the dko strain showed smoother colony morphology on solid agar and irregular shape in transmission electron microscopy. in addition, the dko strain exhibits defective biofilm a ...201525467937
enriching the annotation of mycobacterium tuberculosis h37rv proteome using remote homology detection approaches: insights into structure and function.the availability of the genome sequence of mycobacterium tuberculosis h37rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in m. tuberculosis remain unknown. the emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. here we report the structural and functi ...201525467293
analysis of a draft genome sequence of kitasatospora cheerisanensis kctc 2395 producing bafilomycin antibiotics.kitasatospora cheerisanensis kctc 2395, producing bafilomycin antibiotics belonging to plecomacrolide group, was isolated from a soil sample at mt. jiri, korea. the draft genome sequence contains 8.04 mb with 73.6% g+c content and 7,810 open reading frames. all the genes for aerial mycelium and spore formations were confirmed in this draft genome. in phylogenetic analysis of mure proteins (udp-n-acetylmuramyl-(l)-alanyl-(d)-glutamate:dap ligase) in a conserved dcw (division of cell wall) locus, ...201525471184
bacillus calmette-guérin (bcg) vaccine adverse events in victoria, australia: analysis of reports to an enhanced passive surveillance system.bacillus calmette-guérin (bcg) vaccine is used worldwide, with high efficacy against childhood mycobacterium tuberculosis (tb) meningitis and miliary tb. bcg vaccine is considered safe, with serious systematic adverse events following immunization (aefi) of immunocompetent recipients being rare, although adverse event rates vary between differing bcg strains. in victoria, australia, aefi are reported to saefvic (surveillance of adverse events following vaccination in the community), an enhanced ...201525475539
human b cells produce chemokine cxcl10 in the presence of mycobacterium tuberculosis specific t cells.the role of b cells in human host response to mycobacterium tuberculosis (mtb) infection is still controversial, but recent evidence suggest that b cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment. a candidate for such regulation could be the chemokine cxcl10. cxcl10 is mainly produced by human monocytes, but a few reports have also found cxcl10 production by human b cells. the objective of this study was to investiga ...201525476870
early lesions following aerosol challenge of rhesus macaques (macaca mulatta) with mycobacterium tuberculosis (erdman strain).three rhesus macaques (macaca mulatta) were challenged with mycobacterium tuberculosis (mtb), erdman strain, as part of studies to investigate lesion development at early time points in tuberculosis (tb) and to assess computed tomography (ct) as a method of monitoring disease progression in vivo. animals were challenged with either a high, mid or low dose of aerosolized mtb. the low-dose animal was killed humanely at 24 days post challenge (dpc) and the remaining animals at 25 dpc. abnormalities ...201525481611
hspx knock-out in mycobacterium tuberculosis leads to shorter antibiotic treatment and lower relapse rate in a mouse model--a potential novel therapeutic target.effective global tuberculosis control is hindered by the need for prolonged chemotherapy which leads to poor patient compliance. therefore novel drug targets that shorten the duration of chemotherapy and reduce disease relapse rates are highly desirable. we have previously shown that hspx, an alpha-crystallin-like protein, is associated with growth suppression of mycobacterium tuberculosis in mouse models. we determined to evaluate hspx as a novel target for controlling m. tuberculosis growth in ...201525481272
pyridoxal-phosphate dependent mycobacterial cysteine synthases: structure, mechanism and potential as drug targets.the alarming increase of drug resistance in mycobacterium tuberculosis strains poses a severe threat to human health. chemotherapy is particularly challenging because m. tuberculosis can persist in the lungs of infected individuals; estimates of the who indicate that about 1/3 of the world population is infected with latent tuberculosis providing a large reservoir for relapse and subsequent spread of the disease. persistent m. tuberculosis shows considerable tolerance towards conventional antibi ...201525484279
freund's adjuvant, nod2 and mycobacteria.mycobacterium tuberculosis contributed to the discovery of delayed-type hypersensitivity and cell-mediated immunity. however, the biochemical basis for the immunogenicity of the mycobacterial cell wall has until recently remained unknown.201525483349
effective expansion of forkhead box p3⁺ regulatory t cells via early secreted antigenic target 6 and antigen 85 complex b from mycobacterium tuberculosis.the expansion of cd4+ cd25+ forkhead box (fox)p3+ regulatory t (treg) cells has been observed in patients with mycobacterium (m.) tuberculosis; however, the mechanism of expansion remains to be elucidated. the aim of the present study was to examine the role of the early secreted antigenic target 6(esat‑6) and antigen 85 complex b (ag85b) from m. tuberculosis on treg cell expansion. to investigate the sensitivity of peripheral blood cultures to the m. tuberculosis esat‑6 and ag85b antigens, the ...201525483347
appearances are deceptive: staphylococcus superinfection of clavicular tuberculous osteomyelitis.a man, aged 25 years, presented with pain, swelling, and drainage from the right clavicular area. he had a past history of abscess at the sternoclavicular joint. the cultures from the drainage site grew methicillin-sensitive staphylococcus aureus, and he was placed on appropriate antibiotics. as s. aureus infection of the clavicle is often secondary in nature, particularly in adults, a thorough workup was done to identify the underlying cause. quantiferon gold, done as a part of the workup, came ...201525487239
genotyping and molecular characteristics of multidrug-resistant mycobacterium tuberculosis isolates from china.the aim of this study was to explore the population structure of multidrug-resistant (mdr) tuberculosis strains and distribution of resistance-associated nucleotide alteration among the different genotype mdr strains in china.201525485999
mycobacterial envelope lipids fingerprint from direct maldi-tof ms analysis of intact bacilli.mycobacterium tuberculosis (mtb) lipids including glycolipids and lipoglycans play a crucial role in the modulation of the host immune response by targeting the innate receptors c-type lectins, tlrs and the cd1 proteins of class 1. glycolipids have been shown to be biomarkers of m. tuberculosis strains and also of opportunistic mycobacteria called non-tuberculous mycobacteria. most of the structural and functional work of the mtb lipids has been done using lipids arising from m. tuberculosis cel ...201525488848
quantiferon tb-gold conversion can predict active tuberculosis development in elderly nursing home residents.the study was carried out on elderly nursing home residents in taiwan. we assessed whether the serial quantiferon-tb gold (qft-g) assay and serial tuberculin skin test (tst) were reliable tools to predict or exclude the development of active tuberculosis (tb).201525495670
combinatorial active-site variants confer sustained clavulanate resistance in blac β-lactamase from mycobacterium tuberculosis.bacterial resistance to β-lactam antibiotics is a global issue threatening the success of infectious disease treatments worldwide. mycobacterium tuberculosis has been particularly resilient to β-lactam treatment, primarily due to the chromosomally encoded blac β-lactamase, a broad-spectrum hydrolase that renders ineffective the vast majority of relevant β-lactam compounds currently in use. recent laboratory and clinical studies have nevertheless shown that specific β-lactam-blac inhibitor combin ...201525492589
added value of whole-genome sequencing for management of highly drug-resistant tb.phenotypic drug susceptibility testing (dst) for mycobacterium tuberculosis takes several weeks to complete and second-line dst is often poorly reproducible, potentially leading to compromised clinical decisions. following a fatal case of xdr tb, we investigated the potential benefit of using whole-genome sequencing to generate an in silico drug susceptibility profile.201525492392
[proposal of a five miru-vntr panel to screen clinical isolates of mycobacterium tuberculosis in mexico].tuberculosis is a public health problem across mexico. this paper aims to select a panel, with a minimum number of repetitive elements (miru-vntr) for genotypic characterization of mycobacterium tuberculosis (m. tuberculosis) clinical isolates.201525500299
z-100, extracted from mycobacterium tuberculosis strain aoyama b, promotes tnf-α production via nucleotide-binding oligomerization domain containing 2 (nod2)-dependent nf-κb activation in raw264.7 cells.macrophages are a major component of the innate immune system, and the cytokines they secrete are involved in antitumor responses. z-100 is obtained from hot-water extract of human-type mycobacterium tuberculosis strain aoyama b and activates the innate immune response. however, while z-100 is known to modulate macrophage activity, the mechanism behind this modulation is not fully understood. we evaluated the effects of z-100 on the murine macrophage cell line raw264.7. tumor necrosis factor-alp ...201525499802
computational modeling predicts il-10 control of lesion sterilization by balancing early host immunity-mediated antimicrobial responses with caseation during mycobacterium tuberculosis infection.although almost a third of the world's population is infected with the bacterial pathogen mycobacterium tuberculosis, our understanding of the functions of many immune factors involved in fighting infection is limited. determining the role of the immunosuppressive cytokine il-10 at the level of the granuloma has proven difficult because of lesional heterogeneity and the limitations of animal models. in this study, we take an in silico approach and, through a series of virtual experiments, we pre ...201525512604
potentiation of antigen-specific antibody production by peptides derived from ag85b of mycobacterium tuberculosis.to generate high-titer monoclonal antibodies, strong immuno-stimulation must be used for eliciting an intense cellular immune response. here, we report that antigen-specific antibody production was potentiated by peptide-25 derived from ag85b of mycobacterium tuberculosis, and that the production of antigen-specific igg1 in particular was markedly potentiated; specifically, this occurred because the use of peptide-25 resulted in an increase in the number of antigen-specific antibody-producing ce ...201525514091
mycobacterium tuberculosis 19-kda lipoprotein induces toll-like receptor 2-dependent peroxisome proliferator-activated receptor γ expression and promotes inflammatory responses in human macrophages.mycobacterium tuberculosis (m.tb) enhances its survival in macrophages by suppressing immune responses, in part through its complex cell wall structures. m.tb 19‑kda lipoprotein (p19), a component of the complex cell wall structures of m.tb, is a toll‑like receptor (tlr) agonist, and may induce immune responses through tlr2. furthermore, the activation of peroxisome proliferator‑activated receptor γ (pparγ) is also involved in m.tb‑induced immune responses in macrophages. in the present study, s ...201525504154
evaluation of point mutation detection in mycobacterium tuberculosis with isoniazid resistance using real-time pcr and taqman probe assay.rapid methods for diagnosis of mycobacterium tuberculosis (mtb) drug resistance and choosing appropriate antibiotic treatment are pivotal. thirty isoniazid (inh)-resistant and 30 inh-susceptible mtb isolates were evaluated using minimum inhibitory concentration (mic) method followed by multiplex real-time pcr (rt-pcr). amplification refractory mutation system (arms) for detection of mutation in 315 codon of katg gene and single-nucleotide polymorphism (snp) for detection of mutation in -15 (c>t) ...201525503088
detection of mycobacterium tuberculosis complex in new world monkeys in peru.the mycobacterium tuberculosis complex causes tuberculosis in humans and nonhuman primates and is a global public health concern. standard diagnostics rely upon host immune responses to detect infection in nonhuman primates and lack sensitivity and specificity across the spectrum of mycobacterial infection in these species. we have previously shown that the oral swab pcr (osp) assay, a direct pathogen detection method, can identify the presence of m. tuberculosis complex in laboratory and free-r ...201525515075
frequency of mutations associated with rifampicin resistance in mycobacterium tuberculosis strains isolated from patients in west of iran.tuberculosis (tb) is a devastating infectious disease causing high mortality and morbidity worldwide. the most serious threat related to tuberculosis control is the recent emergence of drug-resistant tuberculosis strains. the aim of the present study was to identify various types of mutations in the rpob region in rifampicin-resistant strains isolated from sputum of tuberculosis patients.201525526063
commensal streptococcus mitis is a unique vector for oral mucosal vaccination.the development of vaccine approaches that induce mucosal and systemic immune responses is critical for the effective prevention of several infections. here, we report on the use of the abundant human oral commensal bacterium streptococcus mitis as a delivery vehicle for mucosal immunization. using homologous recombination we generated a stable rs. mitis expressing a mycobacterium tuberculosis protein (ag85b). oral administration of rs. mitis in gnotobiotic piglets resulted in efficient oral col ...201525522856
correlating minimum inhibitory concentrations of ofloxacin and moxifloxacin with gyra mutations using the genotype mtbdrsl assay.to correlate gyra mutations found on the genotype mtbdrsl assay in mycobacterium tuberculosis (mtb) isolates with minimum inhibitory concentrations (mics) to the fluoroquinolones compounds ofloxacin (ofx) and moxifloxacin (mxf).201525522842
genetic diversity of mycobacterium tuberculosis isolated from tuberculosis patients in the serengeti ecosystem in tanzania.this study was part of a larger cross-sectional survey that was evaluating tuberculosis (tb) infection in humans, livestock and wildlife in the serengeti ecosystem in tanzania. the study aimed at evaluating the genetic diversity of mycobacterium tuberculosis isolates from tb patients attending health facilities in the serengeti ecosystem. dna was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated tb patients aged ≥18 years. spacer oligonucleotide ty ...201525522841
the balance between protective and pathogenic immune responses in the tb-infected lung.tuberculosis is a disease of the lung, and efficient transmission is dependent on the generation of a lesion in the lung, which results in a bacterium-laden cough. mycobacterium tuberculosis (mtb) is able to manipulate both the innate and acquired immune response of the host. this manipulation results in an effective cd4(+) t cell response that limits disease throughout the body but can also promote the development of progressively destructive lesions in the lung. in this way mtb infection can r ...201525521685
polymorphisms in ticam2 and il1b are associated with tb.human genetic susceptibility for tuberculosis (tb) has been demonstrated by several studies, but few have examined the multiple innate and adaptive immunity genes comprehensively, age-specific effects and/or resistance to mycobacterium tuberculosis (mtb) infection (resistors (rstrs)). we hypothesized that rstrs, defined by a persistently negative tuberculin skin test, may have different genetic influences than mtb disease. we examined 29 candidate genes in pathways that mediate immune responses ...201525521228
measurement of phenotype and absolute number of circulating heparin-binding hemagglutinin, esat-6 and cfp-10, and purified protein derivative antigen-specific cd4 t cells can discriminate active from latent tuberculosis infection.the tuberculin skin test (tst) and interferon gamma (ifn-γ) release assays (igras) are used as adjunctive tests for the evaluation of suspected cases of active tuberculosis (tb). however, a positive test does not differentiate latent from active tb. we investigated whether flow cytometric measurement of novel combinations of intracellular cytokines and surface makers on cd4 t cells could differentiate between active and latent tb after stimulation with mycobacterium tuberculosis-specific protein ...201525520147
pooling sputum from multiple individuals for xpert® mtb/rif testing: a strategy for screening high-risk populations.symptom-based screening for tuberculosis (tb) disease is limited by poor performance of symptom screening in several key populations. we tested the hypothesis that pooling sputum from multiple individuals for xpert(®) mtb/rif testing would reduce the number of tests required while retaining an acceptable sensitivity, thus allowing the use of xpert for tb screening.201525519796
accuracy of the xpert® mtb/rif assay for the diagnosis of extra-pulmonary tuberculosis in south korea.the xpert(®) mtb/rif assay has been endorsed by the world health organization for the detection of pulmonary and extra-pulmonary tuberculosis (eptb).201525519795
improved diagnosis of childhood tuberculous meningitis using more than one nucleic acid amplification test.early treatment is critical to reducing tuberculous meningitis (tbm) related morbidity and mortality. diagnosis based on cerebrospinal fluid (csf) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children.201525519794
lewandowsky's rosaceiform eruption: a form of cutaneous tuberculosis confirmed by pcr in two patients.cutaneous tuberculosis (tbc) is a chronic disease caused by mycobacterium tuberculosis, and is present in less than 1-2% of all tbc cases. the current problem with diagnosis is the demonstration of bacillus in the skin, especially paucibacillar forms, where sources like polymerase chain reaction (pcr) have improved diagnostic capacity.201525518812
structures of citrate synthase and malate dehydrogenase of mycobacterium tuberculosis.the tricarboxylic acid (tca) cycle is a central metabolic pathway of all aerobic organisms and is responsible for the synthesis of many important precursors and molecules. tca cycle plays a key role in the metabolism of mycobacterium tuberculosis and is involved in the adaptation process of the bacteria to the host immune response. we present here the first crystal structures of m. tuberculosis malate dehydrogenase and citrate synthase, two consecutive enzymes of the tca, at 2.6 å and 1.5 å reso ...201525524525
immunological consequences of intragenus conservation of mycobacterium tuberculosis t-cell epitopes.a previous unbiased genome-wide analysis of cd4 mycobacterium tuberculosis (mtb) recognition using peripheral blood mononuclear cells from individuals with latent mtb infection (ltbi) or nonexposed healthy controls (hcs) revealed that certain mtb sequences were unexpectedly recognized by hcs. in the present study, it was found that, based on their pattern of reactivity, epitopes could be divided into ltbi-specific, mixed reactivity, and hc-specific categories. this pattern corresponded to sequen ...201525548174
structure of crga, a cell division structural and regulatory protein from mycobacterium tuberculosis, in lipid bilayers.the 93-residue transmembrane protein crga in mycobacterium tuberculosis is a central component of the divisome, a large macromolecular machine responsible for cell division. through interactions with multiple other components including ftsz, ftsq, ftsi (pbpb), pbpa, and cwsa, crga facilitates the recruitment of the proteins essential for peptidoglycan synthesis to the divisome and stabilizes the divisome. crga is predicted to have two transmembrane helices. here, the structure of crga was determ ...201525548160
monkey models of tuberculosis: lessons learned.the use of animal models has been invaluable for studying the pathogenesis of mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. as such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. this review focuses o ...201525547788
ubia (rv3806c) encoding dppr synthase involved in cell wall synthesis is associated with ethambutol resistance in mycobacterium tuberculosis.ethambutol (emb) is a frontline antituberculosis drug for the treatment of tuberculosis (tb). the embb gene is responsible for emb resistance in only about 50-60% clinical isolates of mycobacterium tuberculosis, and the mechanism of resistance in the remaining emb-resistant strains is not clear. we assessed the role of the ubia gene encoding 5-phospho-α-d-ribose-1-diphosphate: decaprenyl-phosphate 5-phosphoribosyltransferase (dppr synthase, ubia) involved in decaprenylphosphoryl-d-arabinose (dpa ...201525547657
arabinosylated lipoarabinomannan (ara-lam) mediated intracellular mechanisms against tuberculosis infection: involvement of protein kinase c (pkc) mediated signaling.tuberculosis causes severe immunosuppression thereby ensuring the loss of the host protective immune responses. during mycobacterium tuberculosis infection, the pathogen modulates tlr-2 receptor down-stream signaling, indicating the possible involvement of tlr-2 in the regulation of the host immune response. moreover, different pkc isoforms are also involved in the course of infection. arabinosylated lipoarabinomannan (ara-lam) possesses immuno-modulatory properties which induce the pro-inflamma ...201525544312
toll-like receptor 1(tlr1) gene snp rs5743618 is associated with increased risk for tuberculosis in han chinese children.toll-like receptor 1 (tlr1) recognizes lipopeptides with tlr2, and affects immune response to mycobacterium tuberculosis infection. here, we report results of the first case-control pediatric study of the tlr1 single-nucleotide polymorphisms and susceptibility to tuberculosis (tb). a pediatric case-control study enrolled 340 tb patients and 366 healthy controls, all han chinese from north china. significant differences of the allelic and genotypic distributions of rs5743618 in tlr1 gene were obs ...201525544311
mycobacterium tuberculosis 38-kda antigen induces endoplasmic reticulum stress-mediated apoptosis via toll-like receptor 2/4.endoplasmic reticulum (er) stress responses play critical roles in the pathogenesis of tuberculosis. to investigate the regulatory role of the er stress response in 38-kda antigen-induced apoptosis, we examined the relationship between the er stress response and apoptosis in bone marrow-derived macrophages (bmdms) stimulated with mycobacterium tuberculosis antigen (38-kda ag). the expression of er molecular chaperones, including c/ebp homologous protein (chop), glucose-regulated protein (bip) an ...201525544271
the complex mechanism of antimycobacterial action of 5-fluorouracil.a combination of chemical genetic and biochemical assays was applied to investigate the mechanism of action of the anticancer drug 5-fluorouracil (5-fu), against mycobacterium tuberculosis (mtb). 5-fu resistance was associated with mutations in upp or pyrr. upp-catalyzed conversion of 5-fu to fump was shown to constitute the first step in the mechanism of action, and resistance conferred by nonsynonymous snps in pyrr shown to be due to derepression of the pyr operon and rescue from the toxic eff ...201525544046
stress and host immunity amplify mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms.nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following "sterilizing" chemotherapy. however, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. here we measure the single-cell dynamics of mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal rna gene expression. single-cell dynamics exhibit heterogeneity under standard ...201525543231
prevalence of mycobacterium tuberculosis strain genotypes in taiwan reveals a close link to ethnic and population migration.taiwan is a relatively isolated island, serving as a mixing vessel for colonization by different waves of ethnic and migratory groups over the past 4 centuries. the potential transmission pattern of mycobacterium tuberculosis in different ethnic and migratory populations remains to be elucidated. by using mycobacterial tandem repeat sequences as genetic markers, the prevalence of m. tuberculosis strains in taiwan revealed a close link to the historical migration. interestingly, the m. tuberculos ...201525542769
exploring the gyrase atpase domain for tailoring newer anti-tubercular drugs: hit to lead optimization of a novel class of thiazole inhibitors.gyrase atpase domain, the pharmaceutical underexploited segment of dna gyrase, the sole type ii topoisomerase present in mycobacterium tuberculosis represents an attractive target for anti-tubercular drug discovery. here we report, the development of a novel series of mtb dna gyraseb inhibitor identified through a medium throughput screening (mts) of bits in-house chemical library (3000 compounds). the mts hit was further remodeled by chemical synthesis to identify the most potent analogue 27 ex ...201525541204
matrix-assisted laser desorption/ionisation time-of-flight (maldi-tof) mass spectrometry (ms) for the identification of mycobacteria from mbbact alert 3d liquid cultures and lowenstein-jensen (lj) solid cultures.conventional methods for the identification of mycobacteria can be demanding and prolonged. molecular methodologies, although rapid, are expensive and often exclusive to reference laboratories. matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (maldi-tof ms) presents a possible alternative method for the identification and differentiation of mycobacteria. this study describes the design and validation of a mycobacteria inactivation protocol and subsequent evaluation of ...201525540267
clinicoradiologic evidence of pulmonary lymphatic spread in adult patients with tuberculosis.the purpose of this study is to evaluate the prevalence and clinicoradiologic characteristics of pulmonary tuberculosis with lymphatic involvement.201525539236
alteration of substrate specificity of alanine dehydrogenase.the l-alanine dehydrogenase (aladh) has a natural history that suggests it would not be a promising candidate for expansion of substrate specificity by protein engineering: it is the only amino acid dehydrogenase in its fold family, it has no sequence or structural similarity to any known amino acid dehydrogenase, and it has a strong preference for l-alanine over all other substrates. by contrast, engineering of the amino acid dehydrogenase superfamily members has produced catalysts with expande ...201525538307
effects of cho-expressed recombinant lactoferrins on mouse dendritic cell presentation and function.lactoferrin (lf), a natural iron-binding protein, has previously demonstrated effectiveness in enhancing the bacillus calmette-guérin (bcg) tuberculosis vaccine. this report investigates immune modulatory effects of chinese hamster ovary (cho) cell-expressed recombinant mouse and human lfs on mouse bone marrow-derived dendritic cells (bmdcs), comparing homologous and heterologous functions. bcg-infected bmdcs were cultured with lf, and examined for class ii presentation molecule expression. cult ...201525537452
espr, a regulator of the esx-1 secretion system in mycobacterium tuberculosis, is directly regulated by the two-component systems mprab and phopr.the regulatory mechanisms that control the esx-1 secretion system, a key player in the pathogenesis of mycobacterium tuberculosis, have not been fully elucidated. however, factors that regulate the esx-1 substrate espa usually affect esx-1 function. previous studies showed that espa is directly regulated by the nucleoid-associated protein espr and the two-component system (tcs) mprab. the phopr tcs also activates espa, but the direct target of phop was unknown. in this report, we reveal that esp ...201525536998
the impact of hiv exposure and maternal mycobacterium tuberculosis infection on infant immune responses to bacille calmette-guérin vaccination.the objective of this study is to assess the effect of maternal hiv and mycobacterium tuberculosis (mtb) infection on cellular responses to bacille calmette-guérin (bcg) immunization.201525535752
phosphorylation control of protein tyrosine phosphatase a activity in mycobacterium tuberculosis.protein tyrosine phosphatase a (ptpa) has been shown to play a key role in human macrophage infection by mycobacterium tuberculosis (mtb). protein tyrosine kinase a (ptka) was the first protein tyrosine kinase shown to phosphorylate ptpa. here, we found that ptka-mediated phosphorylation of ptpa on tyr-128 and tyr-129 enhances the ptpa phosphatase activity. moreover, ex-vivo protein-protein interaction assays showed that ptpa can be phosphorylated by several eukaryotic-like ser/thr protein kinas ...201525535696
a terd domain-encoding gene (sco2368) is involved in calcium homeostasis and participates in calcium regulation of a dosr-like regulon in streptomyces coelicolor.although streptomyces coelicolor is not resistant to tellurite, it possesses several terd domain-encoding (tdd) genes of unknown function. to elucidate the function of tdd8, the transcriptomes of s. coelicolor strain m145 and of a tdd8 deletion mutant derivative (the δtdd8 strain) were compared. several orthologs of mycobacterium tuberculosis genes involved in dormancy survival were upregulated in the deletion mutant at the visual onset of prodiginine production. these genes are organized in a p ...201525535276
functional drug screening reveals anticonvulsants as enhancers of mtor-independent autophagic killing of mycobacterium tuberculosis through inositol depletion.mycobacterium tuberculosis (mtb) remains a major challenge to global health made worse by the spread of multidrug resistance. we therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. despite the resistance of mtb to killing by basal autophagy, cell-based screening of fda-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate a ...201525535254
molecular diagnosis of fluoroquinolone resistance in mycobacterium tuberculosis.as a consequence of the use of fluoroquinolones (fq), resistance to fq has emerged, leading to cases of nearly untreatable and extensively drug-resistant tuberculosis. mutations in dna gyrase represent the main mechanism of fq resistance. a full understanding of the pattern of mutations found in fq-resistant (fq(r)) clinical isolates, and of their proportions, is crucial for improving molecular methods for the detection of fq resistance in mycobacterium tuberculosis. in this study, we reviewed t ...201525534742
the efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. in this study, we used timcodar (formerly vx-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-tb) drugs against mycobacterium tuberculosis in in vitro and in vivo combination studies. when used alone, timcodar weakly inhibited m. tuberculosis growth in broth culture (mic, 19 μg/ml); however, it demonstrated synergism in drug combination studies with rifamp ...201525534740
design, synthesis, and biological evaluation of 1,4-dihydropyridine derivatives as potent antitubercular agents.a series of novel 1,4-dihydropyridine-3,5-dicarbamoyl derivatives bearing an imidazole nucleus at c-4 position were synthesized in excellent yields via multicomponent hantzsch reaction. the newly synthesized compounds were characterized by ir, (1) h nmr, (13) c nmr, and mass spectroscopy. the synthesized compounds 3a-p were screened for antitubercular activity. among all the screened compounds, compounds 3j and 3m showed most prominent activity against mycobacterium tuberculosis with minimum inh ...201525534154
absence of annexin a1 impairs host adaptive immunity against mycobacterium tuberculosis in vivo.the role of annexin a1 (anxa1) in counter-regulating the activities of innate immune cells, such as the migration of neutrophils and monocytes, and the generation of pro-inflammatory mediators in various models of inflammatory and autoimmune diseases is well documented. however, while anxa1 has been proposed as an important mediator of the adaptive immune response, its involvement in this respect has been less studied. furthermore, while there have been numerous studies on the role of anxa1 in i ...201525533809
real-time fluorescence loop-mediated isothermal amplification (lamp) for rapid and reliable diagnosis of pulmonary tuberculosis.a reliable, simple and rapid diagnostic method that can be helpful in pulmonary tuberculosis diagnosis is urgently needed. loop-mediated isothermal amplification (lamp) allows dna to be amplified rapidly at a constant temperature. in this study, real-time fluorescence lamp was evaluated to rapidly detect mycobacterium tuberculosis in sputum and was compared to the performance of real-time fluorescence quantitative pcr (q-pcr). all the standard mtb strains were successfully detected and limit of ...201525533219
association between interleukin-1 receptor antagonist (il1rn) variable number of tandem repeats (vntr) polymorphism and pulmonary tuberculosis.macrophages and t-lymphocytes are involved in immune response to mycobacterium tuberculosis. macrophage produces interleukin (il)-1 as an inflammatory mediator. il-1 receptor antagonist (il1-ra) is a natural antagonist of il-1 receptors. in this study we aimed to examine the possible association between the variable number of tandem repeats (vntr) of the il-1 receptor antagonist (il1rn) gene and pulmonary tuberculosis (tb) in a sample of iranian population. our study is a case-control study and ...201525530139
ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis.the ratio of monocytes to lymphocytes in peripheral blood could reflect an individual's immunity to mycobacterium tuberculosis. the objective of this study was to evaluate the relationship between ratio of monocytes to lymphocytes and clinical status of patients with active tuberculosis.201525529365
factors associated with tuberculosis infection, and with anti-mycobacterial immune responses, among five year olds bcg-immunised at birth in entebbe, uganda.bcg is used widely as the sole licensed vaccine against tuberculosis, but it has variable efficacy and the reasons for this are still unclear. no reliable biomarkers to predict future protection against, or acquisition of, tb infection following immunisation have been identified. lessons from bcg could be valuable in the development of effective tuberculosis vaccines.201525529292
synthesis and antibacterial activity of alkylated diamines and amphiphilic amides of quinic acid derivatives.different series of n-alkylated diamines and their derivatives condensed to quinic acid were synthesized and tested for antibacterial properties against staphylococcus aureus, staphylococcus epidermidis, pseudomonas aeruginosa, and mycobacterium tuberculosis. the lipophilic chain and carbohydrate moiety modulate the antibacterial activity and the compounds showed a structure-activity relationship. overall, 11 compounds displayed better activity than chloramphenicol against gram-positive and gram ...201525528858
diagnostic performance of a cytokine and ifn-γ-induced chemokine mrna assay after mycobacterium tuberculosis-specific antigen stimulation in whole blood from infected individuals.interferon (ifn)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (tb) disease and latent tb infection (ltbi). numerous cytokines and regulator factors have been implicated in the pathogenesis and control of mycobacterium tuberculosis infection. additional cytokines and chemokines associated with m. tuberculosis infection may improve the performance of ifn-γ release assays. we developed a real-time rt-pcr taqman assay for targeting levels of eight hu ...201525528189
finer characterization of mycobacterium tuberculosis using spoligotyping and 15-loci miru-vntrs reveals phylogeographical specificities of isolates circulating in guyana and suriname.in this study we used spoligotyping and 15-loci miru-vntrs for a finer characterization of mycobacterium tuberculosis strains isolated from patients residing in guyana (n=74) and suriname (n=80). the mean age of the patients was 38.5years (36.5 and 40.2years for guyana vs. suriname), with a male-to-female sex-ratio of 2.25 for guyana vs. 4.27 in suriname. spoligotyping and 15-loci miru-vntrs led to a total of 41 and 65 different patterns respectively, with an overall clustering rate of 83.8% vs. ...201525528138
lag3 expression in active mycobacterium tuberculosis infections.mycobacterium tuberculosis (mtb) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. mtb modulates several aspects of the host immune response. lymphocyte-activation gene 3 (lag3) is a protein with a high affinity for the cd4 receptor and is expressed mainly by regulatory t cells with immunomodulatory functions. to understand the function of lag3 during mtb infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects ...201525549835
construction of recombinant fusion protein of influenza, a virus neuraminidase and heat shock protein 70 gene: expression in baculovirus and bioactivity.background: two structural antigens, hemagglutinin and neuraminidase, are a major component for the development of influenza vaccine candidates. recombinant vaccines are produced by a simple method, although expected to induce an immune response to a specific antigen, remaining to be further improved for their high effectiveness. in general, heat shock protein 70 of mycobacterium tuberculosis, as a potent adjuvant, is commonly used to improve antigen-presenting cell (apc) function and thereby el ...201528316730
tissue microarray technology for molecular applications: investigation of cross-contamination between tissue samples obtained from the same punching device.tissue microarray (tma) technology allows rapid visualization of molecular markers by immunohistochemistry and in situ hybridization. in addition, tma instrumentation has the potential to assist in other applications: punches taken from donor blocks can be placed directly into tubes and used for nucleic acid analysis by pcr approaches. however, the question of possible cross-contamination between samples punched with the same device has frequently been raised but never addressed.201527600219
unusual location of tuberculosis in the course of tumor necrosis factor α inhibitor therapy.tuberculosis is an infectious disease caused by mycobacterium tuberculosis complex mycobacteria. extrapulmonary tuberculosis usually develops more than two years after infection or many years later. factors favoring onset of the disease are malnutrition, older age, renal failure, diabetes, cancer, immunosuppression and biological treatment, e.g. tumor necrosis factor α (tnf-α) inhibitors. the paper presents a case of a 56-year-old patient with ankylosing spondylitis treated with infliximab, diag ...201527407244
genitourinary presentation of tuberculosis.tuberculosis (tb) is less common in developed countries; however, the incidence of tb-especially resistant strains-is on the rise worldwide. cases of tb manifesting as urologic complications are rare in the united states. urologists should be aware of this potential manifestation, especially in patients who have recently immigrated to the united states or have traveled abroad for prolonged periods. two cases are presented here to illustrate this entity.201527222648
drug resistance and population structure of mycobacterium tuberculosis beijing strains isolated in poland.in total, 1095 mycobacterium tuberculosis clinical isolates from 282 patients with drug-resistant and 813 with drug-sensitive tuberculosis (tb) in poland during 2007-2011 were analysed. seventy-one (6.5%) patients were found to have strains of beijing genotype as defined by spoligotyping. the majority of patients were polish-born; among foreign-born a large proportion came from chechnya and vietnam. analysis showed strong associations between beijing genotype infection and mdr, pre-xdr and xdr r ...201526999963
five years' evaluation of the bd probetec system for the direct molecular detection of mycobacterium tuberculosis complex in respiratory and nonrespiratory clinical samples.in this study, mycobacterium tuberculosis complex was detected by bd probetec et system in 4716 respiratory and 167 nonrespiratory samples [mostly (98%) smear negative). sensitivity, specificity, positive and negative predictive values were 81.8%, 98.3, 85.1 and 97.9 for respiratory and 100%, 96.2, 64.7 and 100, for nonrespiratory samples, respectively. among 149 (3.1%) probetec dtb positive and culture negative samples, 72 (65 respiratory and seven nonrespiratory) (48.3%) were recovered from th ...201526999961
genotypic and phenotypic characteristics of aminoglycoside-resistant mycobacterium tuberculosis isolates in latvia.mutations causing resistance to aminoglycosides, such as kanamycin (kan), amikacin (amk), and streptomycin, are not completely understood. in this study, polymorphisms of aminoglycoside resistance influencing genes such as rrs, eis, rpsl, and gidb in 41 drug-resistant and 17 pan-sensitive mycobacterium tuberculosis clinical isolates in latvia were analyzed. mutation a1400g in rrs gene was detected in 92% isolates with high resistance level to kan and diverse mic level to amk. mutations in promot ...201525557624
use of a "silver bullet" to resolve crystal lattice dislocation disorder: a cobalamin complex of δ1-pyrroline-5-carboxylate dehydrogenase from mycobacterium tuberculosis.the use of small molecules as "silver bullets" that can bind to generate crosslinks between protein molecules has been advanced as a powerful means of enhancing success in protein crystallization (mcpherson and cudney, 2006). we have explored this approach in attempts to overcome an order-disorder phenomenon that complicated the structural analysis of the enzyme δ(1)-pyrroline-5-carboxylate dehydrogenase from mycobacterium tuberculosis (p5cdh, mtb-prua). using the silver bullets bio screen, we o ...201525557497
performance of a real-time pcr assay for the rapid identification of mycobacterium species.mycobacteria cause a variety of illnesses that differ in severity and public health implications. the differentiation of mycobacterium tuberculosis (mtb) from nontuberculous mycobacteria (ntm) is of primary importance for infection control and choice of antimicrobial therapy. the diagnosis of diseases caused by ntm is difficult because ntm species are prevalent in the environment and because they have fastidious properties. in the present study, we evaluated 279 clinical isolates grown in liquid ...201525557479
target-based identification of whole-cell active inhibitors of biotin biosynthesis in mycobacterium tuberculosis.biotin biosynthesis is essential for survival and persistence of mycobacterium tuberculosis (mtb) in vivo. the aminotransferase bioa, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. we performed high-throughput screening (hts) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (dos) scaffolds. to efficie ...201525556942
different behaviours of promoters in mycobacterium tuberculosis h37rv and h37ra.mycobacterium tuberculosis h37rv and h37ra are two closely-related bacterial strains in which the former is virulent whereas the latter is not. although the genetic differences between these strains are known, our understanding of how they control the difference in virulence characteristics is incomplete. in this work, we tested the activities of different mycobacterium gene promoters in the two strains using a gfp reporter gene. the promoter activities were compared between growth in vitro and ...201525556328
synthesis, antimycobacterial and antifungal evaluation of some new 1-ethyl-5-(hetero)aryl-6-styryl-1,6-dihydropyrazine-2,3-dicarbonitriles.the petasis reaction of 6-hydroxy adducts of 1-alkyl-2,3-dicyano-5-arylpyrazinium salts with trans-styrylboronic acids proved to proceed smoothly at room temperature to give the corresponding 5-(hetero)aryl-6-styryl substituted 1,6-dihydropyrazine derivatives. also it has been found that c(6) unsubstituted 1,6-dihydro- or 1,4,5,6-tetrahydropyrazine derivatives can be easy prepared in high yields from the corresponding pyrazinium salts by reduction with triethylsilane. all synthesized compounds w ...201525556103
magnitude and sources of bias in the detection of mixed strain m. tuberculosis infection.high resolution tests for genetic variation reveal that individuals may simultaneously host more than one distinct strain of mycobacterium tuberculosis. previous studies find that this phenomenon, which we will refer to as "mixed infection", may affect the outcomes of treatment for infected individuals and may influence the impact of population-level interventions against tuberculosis. in areas where the incidence of tb is high, mixed infections have been found in nearly 20% of patients; these s ...201525553967
evaluation of the meltpro tb/str assay for rapid detection of streptomycin resistance in mycobacterium tuberculosis.rapid and comprehensive detection of drug-resistance is essential for the control of tuberculosis, which has facilitated the development of molecular assays for the detection of drug-resistant mutations in mycobacterium tuberculosis. we hereby assessed the analytical and clinical performance of an assay for streptomycin-resistant mutations. meltpro tb/str is a closed-tube, dual-color, melting curve analysis-based, real-time pcr test designed to detect 15 streptomycin-resistant mutations in rpsl ...201525553930
differential transcriptional response in macrophages infected with cell wall deficient versus normal mycobacterium tuberculosis.host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (mtb). under adverse circumstances, normal mtb can form cell-wall deficient (cwd) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. however, the molecular mechanism by which infection of macrophages with different phenotypic mtb elicits distinct responses of macrophages is not fully understood. to explore the molecul ...201525552926
comparison of the genedia mtb detection kit and the cobas taqman mtb assay for detection of mycobacterium tuberculosis in respiratory specimens.the performance of the genedia mtb detection kit was compared with that of the cobas taqman mtb test using respiratory specimens. the genedia and cobas assays showed comparable sensitivities (81.8% and 78.8%, respectively) and specificities (99.8% and 99.5%, respectively), while the genedia assay produced fewer invalid results and required less turnaround time and labor.201525568443
direct inhibitors of inha are active against mycobacterium tuberculosis.new chemotherapeutic agents are urgently required to combat the global spread of multidrug-resistant tuberculosis (mdr-tb). the mycobacterial enoyl reductase inha is one of the few clinically validated targets in tuberculosis drug discovery. we report the identification of a new class of direct inha inhibitors, the 4-hydroxy-2-pyridones, using phenotypic high-throughput whole-cell screening. this class of orally active compounds showed potent bactericidal activity against common isoniazid-resist ...201525568071
rapid detection of rifampin-resistant clinical isolates of mycobacterium tuberculosis by reverse dot blot hybridization.a pcr-reverse dot blot hybridization (rdbh) assay was developed for rapid detection of rpob gene mutations in 'hot mutation region' of mycobacterium tuberculosis (m. tuberculosis).201525566860
fragment-based strategy for investigating and suppressing the efflux of bioactive small molecules.membrane protein-mediated drug efflux is a phenomenon that compromises our ability to treat both infectious diseases and cancer. accordingly, there is much interest in the development of strategies for suppression of the mechanisms by which therapeutic agents are effluxed. here, using resistance to the cyclic acyldepsipeptide (adep) antibacterial agents as a model, we demonstrate a new counter-efflux strategy wherein a fragment of an actively exported bioactive compound competitively interferes ...201527620145
detection of mycobacterium tuberculosis based on h37r(v) binding peptides using surface functionalized magnetic microspheres coupled with quantum dots – a nano detection method for mycobacterium tuberculosis.despite suffering from the major disadvantage of low sensitivity, microscopy of direct smear with the ziehl-neelsen stain is still broadly used for detection of acid-fast bacilli and diagnosis of tuberculosis. here, we present a unique detection method of mycobacterium tuberculosis (mtb) using surface functionalized magnetic microspheres (mmss) coupled with quantum dots (qds), conjugated with various antibodies and phage display-derived peptides. the principle is based upon the conformation of t ...201525565805
tuberculosis of the triceps muscle.a tubercular swelling of the triceps muscle in a 25-year-old immunocompetent man is described in this report. he presented with hard, fixed swelling at the lower end of the triceps muscle. confirmatory diagnosis was established by fine-needle aspiration cytology (fnac) of the swelling with subsequent pcr for mycobacterium tuberculosis of the fnac specimen. the patient was completely cured with antitubercular therapy.201525564636
attomolar quantitation of mycobacterium tuberculosis by asymmetric helicase-dependent isothermal dna-amplification and electrochemical detection.a highly sensitive and robust method for the quantification of specific dna sequences based on coupling asymmetric helicase-dependent dna amplification to electrochemical detection is described. this method relies on the entrapment of the amplified ssdna sequences on magnetic beads followed by a post-amplification hybridization assay to provide an added degree of specificity. as a proof-of-concept a 84-bases long sequence specific of mycobacterium tuberculosis is amplified at 65°c, providing 3×1 ...201525562738
structural basis of ligand binding to udp-galactopyranose mutase from mycobacterium tuberculosis using substrate and tetrafluorinated substrate analogues.udp-galactopyranose mutase (ugm) is a flavin-containing enzyme that catalyzes the reversible conversion of udp-galactopyranose (udp-galp) to udp-galactofuranose (udp-galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. a soluble, active form of ugm from mycobacterium tuberculosis (mtugm) was obtained from a dual his6-mbp-tagged mtugm construct. we present the first complex structures of mtugm with bound substrate udp-galp (both oxidized flavin and reduced f ...201525562380
annexin1 regulates dc efferocytosis and cross-presentation during mycobacterium tuberculosis infection.the phagocytosis of apoptotic cells and associated vesicles (efferocytosis) by dcs is an important mechanism for both self tolerance and host defense. although some of the engulfment ligands involved in efferocytosis have been identified and studied in vitro, the contributions of these ligands in vivo remain ill defined. here, we determined that during mycobacterium tuberculosis (mtb) infection, the engulfment ligand annexin1 is an important mediator in dc cross-presentation that increases effer ...201525562320
biology of il-27 and its role in the host immunity against mycobacterium tuberculosis.il-27, a heterodimeric cytokine of il-12 family, regulates both innate and adaptive immunity largely via jak-stat signaling. il-27 can induce ifn-γ and inflammatory mediators from t lymphocytes and innate immune cells. il-27 has unique anti-inflammatory properties via both tr1 cells dependent and independent mechanisms. here the role and biology of il-27 in innate and adaptive immunity are summarized, with special interest with immunity against mycobacterium tuberculosis.201525561899
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