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a summary of the third global interferon-γ release assay symposium.studies over the past several decades have dramatically increased our understanding of the immune response to mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (ifn-γ) release assays (igras), which appear to obviate many of the problems encountered with the tuberculin skin test (tst). worldwide, 2 igras are currently commercially available. quantiferon-tb gold in-tube (cellestis) is a third-genera ...201323651894
mycobacterium tuberculosis infection is associated with the development of erythema nodosum and nodular vasculitis.mycobacterium tuberculosis (mtb) infection has been suggested to contribute to the pathogenesis of erythema nodosum (en) and nodular vasculitis (nv), the classic forms of panniculitis. however, there is little evidence to demonstrate the presence of mtb in the skin lesions. this study is aimed at evaluating the association between mtb infection and the development of en and nv in a chinese population.201323650522
mycobacterial toxin mazf-mt6 inhibits translation through cleavage of 23s rrna at the ribosomal a site.the mycobacterium tuberculosis genome contains an unusually high number of toxin-antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. nine of these toxin-antitoxin loci belong to the mazef family, encoding the intracellular toxin mazf and its antitoxin inhibitor maze. nearly every mazf ortholog recognizes a unique three- or five-base rna sequence and cleaves mrna. as a result, these toxins selectively target a subset of ...201323650345
comparison of gene expression profiles between pansensitive and multidrug-resistant strains of mycobacterium tuberculosis.mycobacterium tuberculosis has developed resistance to anti-tuberculosis first-line drugs. multidrug-resistant strains complicate the control of tuberculosis and have converted it into a worldwide public health problem. mutational studies of target genes have tried to envisage the resistance in clinical isolates; however, detection of these mutations in some cases is not sufficient to identify drug resistance, suggesting that other mechanisms are involved. therefore, the identification of new ma ...201323649743
snp typing reveals similarity in mycobacterium tuberculosis genetic diversity between portugal and northeast brazil.human tuberculosis is an infectious disease caused by bacteria from the mycobacterium tuberculosis complex (mtbc). although spoligotyping and miru-vntr are standard methodologies in mtbc genetic epidemiology, recent studies suggest that single nucleotide polymorphisms (snp) are advantageous in phylogenetics and strain group/lineages identification. in this work we use a set of 79 snps to characterize 1987 mtbc isolates from portugal and 141 from northeast brazil. all brazilian samples were furth ...201323648425
transmission of mycobacterium tuberculosis beijing strains, alberta, canada, 1991-2007.beijing strains are speculated to have a selective advantage over other mycobacterium tuberculosis strains because of increased transmissibility and virulence. in alberta, a province of canada that receives a large number of immigrants, we conducted a population-based study to determine whether beijing strains were associated with increased transmission leading to disease compared with non-beijing strains. beijing strains accounted for 258 (19%) of 1,379 pulmonary tuberculosis cases in 1991-2007 ...201323648234
tuberculosis exposure among evacuees at a shelter after earthquake, japan, 2011.tuberculosis was diagnosed in a person who had stayed in a shelter after the 2011 great east japan earthquake. a contact investigation showed that the prevalence of latent tuberculosis infection among other evacuees at the shelter was 20%. our report underscores the importance of tuberculosis prevention and control after natural disasters.201323648069
prevalence of tuberculosis in pigs slaughtered at two abattoirs in ethiopia and molecular characterization of mycobacterium tuberculosis isolated from tuberculous-like lesions in pigs.tuberculosis (tb) is an infectious, granulomatous disease caused by acid-fast bacilli of the genus mycobacterium. the disease affects practically all species of vertebrates. although mammalian tuberculosis has been nearly controlled in many developed countries, it is still a serious problem in humans and domestic animals including pigs in developing countries. in ethiopia, the prevalence of tb in pigs is not known. therefore, this study was designed to estimate the prevalence of tb in pigs in ce ...201323647845
a novel quinoline derivative that inhibits mycobacterial ftsz.high throughput phenotypic screening of large commercially available libraries through two nih programs has produced thousands of potentially interesting hits for further development as antitubercular agents. unfortunately, these screens do not supply target information, and further follow up target identification is required to allow optimal rational design and development of highly active and selective clinical candidates. cheminformatic analysis of the quinoline and quinazoline hits from thes ...201323647650
anti-tubercular agents. part 7: a new class of diarylpyrrole-oxazolidinone conjugates as antimycobacterial agents.in an effort to discover new anti-tubercular agents, a series of new diarylpyrrole-oxazolidinone conjugates have been designed and synthesized. the anti-tubercular activity of these new conjugates (4a-n and 5a-d) against mycobacterium tuberculosis h37rv and drug resistance strains such as m. tuberculosis rif(r) and m. tuberculosis xdr are discussed, wherein compound 4i has been found to be the most potent amongst the series. mtt assay was performed on the active conjugates of the series (4b-f, 4 ...201323644207
identification of the monocyte activating motif in mycobacterium tuberculosis chaperonin 60.1.evidence is emerging that moonlighting proteins, defined as proteins with more than one biological function, play important roles in bacterial virulence. the mycobacterium tuberculosis chaperone, chaperonin 60.1, is a potent stimulator of human monocyte cytokine synthesis and modulator of giant cell and osteoclast formation. previously, we had shown that these moonlighting activities resided in the equatorial domain of this protein. in this study, through the generation of chaperonin 60.1 amino ...201323643849
crystal structure of mycobacterium tuberculosis rv2606c: a pyridoxal biosynthesis lyase.tuberculosis is a lethal infectious disease caused by mycobacterium tuberculosis. we determined the crystal structure of rv2606c, a potential pyridoxal biosynthesis lyase (pdxs), from m. tuberculosis h37rv at 1.8 å resolution. the overall structure of the protein, composed of a (β/α)8-barrel and two small 310-helices, was quite similar to those of other pdxs proteins. a glycerol molecule was observed to be bound at the active site of the rv2606c structure through interactions with the conserved ...201323643787
mycobacterium tuberculosis, how long did you walk? 201523643639
recruitment of th1 effector cells in human tuberculosis: hierarchy of chemokine receptor(s) and their ligands.selective recruitment of ifn-γ biased th1 effector cells at the pathologic site(s) determines the local immunity of tuberculosis (tb). we observed the enrichment of cxcr3, ccr5 and cd11a(high) t cells in the peripheral blood, pleural fluid and bronchoalveolar lavage of tb pleural effusion (tb-pe) and miliary tuberculosis (mtb) patients respectively. cxcr3(+)ccr5(+) t cells were significantly high at the local disease site(s) in both the forms of tb and their frequency was highest among activated ...201323643185
proteases in mycobacterium tuberculosis pathogenesis: potential as drug targets.tb is still a major global health problem causing over 1 million deaths per year. an increasing problem of drug resistance in the causative agent, mycobacterium tuberculosis, as well as problems with the current lengthy and complex treatment regimens, lends urgency to the need to develop new antitubercular agents. proteases have been targeted for therapy in other infections, most notably these have been successful as antiviral agents in the treatment of hiv infection. m. tuberculosis has a numbe ...201323642117
adjuvant host-directed therapy with types 3 and 5 but not type 4 phosphodiesterase inhibitors shortens the duration of tuberculosis treatment.shortening tuberculosis treatment could significantly improve patient adherence and decrease the development of drug resistance. phosphodiesterase inhibitors (pde-is) have been shown to be beneficial in animal models of tuberculosis. we assessed the impact of pde-is on the duration of treatment in tuberculous mice.201323641020
enhanced immune response and protective effects of nano-chitosan-based dna vaccine encoding t cell epitopes of esat-6 and fl against mycobacterium tuberculosis infection.development of a novel and effective vaccine against mycobacterium tuberculosis (m.tb) is a challenging for preventing tb infection. in this study, a novel nanoparticle-based recombinant dna vaccine was developed, which contains esat-6 three t cell epitopes (esat-6/3e) and fms-like tyrosine kinase 3 ligand (fl) genes (termed esat-6/3e-fl), and was enveloped with chitosan (cs) nanoparticles (nano-chitosan). the immunologic and protective efficacy of the nano-chitosan-based dna vaccine (termed nan ...201323637790
evaluation of a pro-active strategy for managing tuberculosis-hiv co-infection in a uk tertiary care setting.management of tuberculosis (tb)-hiv co-infection is complicated by interactions between the diseases and their therapies. we developed and evaluated a strategy to (i) treat co-infected patients in a single co-infection clinic, (ii) maximize use of first-line drugs, (iii) delay antiretroviral therapy (art) until two months post-tb treatment except in severe immunosuppression, (iv) commence efavirenz at 600 mg daily with therapeutic drug monitoring (tdm) and (v) target treatment completion. we con ...201323635810
phylogenetic lineages of tuberculosis isolates in new zealand and their association with patient demographics.in new zealand, the lineage genotypes of mycobacterium tuberculosis clinical isolates and their role in the epidemiology of tuberculosis (tb) are currently unknown.201323635796
mycobacterium tuberculosis- induced neutrophil extracellular traps activate human macrophages.neutrophils activated by mycobacterium tuberculosis (mtb) form neutrophil extracellular traps (nets), containing dna and several biologically active cytosolic and granular proteins. these nets may assist in the innate immune defense against different pathogens. we investigated whether the net-forming neutrophils mediate an activating signal to macrophages during the early multicellular inflammatory reaction and granuloma formation. mtb-induced nets were found to be reactive oxygen species depend ...201323635526
genetic diversity of the mycobacterium tuberculosis complex in san luis potosí, méxico.although epidemiologic and socioeconomic criteria and biomedical risk factors indicate high-priority for tuberculosis (tb) control in mexico, molecular epidemiology studies of the disease in the country are scarce.201323635381
design of thymidine analogues targeting thymidilate kinase of mycobacterium tuberculosis.we design here new nanomolar antituberculotics, inhibitors of mycobacterium tuberculosis thymidine monophosphate kinase (tmpkmt), by means of structure-based molecular design. 3d models of tmpkmt-inhibitor complexes have been prepared from the crystal structure of tmpkmt cocrystallized with the natural substrate deoxythymidine monophosphate (dtmp) (1gsi) for a training set of 15 thymidine analogues (tmds) with known activity to prepare a qsar model of interaction establishing a correlation betwe ...201323634301
inhibition of nuclear factor-kappa b activation decreases survival of mycobacterium tuberculosis in human macrophages.nuclear factor-kappa b (nfκb) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, nfκb has been implicated in the pathogenesis of other inflammatory and infectious diseases. mice with genetic disruption of the p50 subunit of nfκb are more likely to succumb to mycobacterium tuberculosis (mtb). however, the role of nfκb in host defense in humans is not fully understood. we sought to examine the role ...201323634218
linkage of presumptive multidrug resistant tuberculosis (mdr-tb) patients to diagnostic and treatment services in cambodia.national tuberculosis programme, cambodia.201323634202
tuberculous pyomyositis: a rare but serious diagnosis.tuberculous pyomyositis is a rare clinical entity with serious consequences if a diagnosis is not established early. a 53-year-old female with a past medical history of sarcoidosis and pulmonary fibrosis presented from an outside hospital with persistent fevers and a rash. she had been hospitalized multiple times at an outside hospital without any improvement in her symptoms. on examination, she was noted to have a large area of left upper lower extremity (lue) tenderness with superimposed eryth ...201323634147
rapid in vivo assessment of drug efficacy against mycobacterium tuberculosis using an improved firefly luciferase.in vivo experimentation is costly and time-consuming, and presents a major bottleneck in anti-tuberculosis drug development. conventional methods rely on the enumeration of bacterial colonies, and it can take up to 4 weeks for mycobacterium tuberculosis to grow on agar plates. light produced by recombinant bacteria expressing luciferase enzymes can be used as a marker of bacterial load, and disease progression can be easily followed non-invasively in live animals by using the appropriate imaging ...201323633686
rifampicin-resistant and rifabutin-susceptible mycobacterium tuberculosis strains: a breakpoint artefact?it has long been assumed that some rifampicin-resistant mycobacterium tuberculosis strains are susceptible to, and thus treatable with, rifabutin. however, clinical breakpoints for susceptibility testing of rifabutin as well as the evidence for a clinical effect of rifabutin in rifampicin-resistant strains remains poorly defined. the objective of this study was to re-evaluate the breakpoint for rifabutin in relation to its mic wild-type distribution and the presence of mutations in rpob.201323633684
dna metabolism in mycobacterial pathogenesis.fundamental aspects of the lifestyle of mycobacterium tuberculosis implicate dna metabolism in bacillary survival and adaptive evolution. the environments encountered by m. tuberculosis during successive cycles of infection and transmission are genotoxic. moreover, as an obligate pathogen, m. tuberculosis has the ability to persist for extended periods in a subclinical state, suggesting that active dna repair is critical to maintain genome integrity and bacterial viability during prolonged infec ...201323633106
[bacteriological substantiation of the antituberculosis effect of immunotropic drug tubosan].the antituberculosis effect of tubosan registered in the russian federation as an immunostimulant drug has been studied on a series of 53 clinical strains of mycobacterium tuberculosis (mbt). it is established that tubosan produces a bactericidal effect on drug-sensitive mbt strains and a bacteriostatic effect on resistant mbt strains. use of tubosan for the treatment of 102 patients with drug-resistant destructive tuberculosis showed evident clinical-radiological involution process, with prospe ...201323631279
detection of rifampicin resistance in mycobacterium tuberculosis by padlock probes and magnetic nanobead-based readout.control of the global epidemic tuberculosis is severely hampered by the emergence of drug-resistant mycobacterium tuberculosis strains. molecular methods offer a more rapid means of characterizing resistant strains than phenotypic drug susceptibility testing. we have developed a molecular method for detection of rifampicin-resistant m. tuberculosis based on padlock probes and magnetic nanobeads. padlock probes were designed to target the most common mutations associated with rifampicin resistanc ...201323630621
genetic and shared environmental influences on interferon-γ production in response to mycobacterium tuberculosis antigens in a ugandan population.interferon-γ (ifn-γ) is a key cytokine in the immune response to mycobacterium tuberculosis (mtb). many studies established ifn-γ responses are influenced by host genetics, however differed widely by the study design and heritability estimation method. we estimated heritability of ifn-γ responses to mtb culture filtrate (cf), esat-6, and antigen 85b (ag85b) in 1,104 ugandans from a household contact study. our method separately evaluates shared environmental and genetic variance, therefore herit ...201323629934
social networks to biological networks: systems biology of mycobacterium tuberculosis.contextualizing relevant information to construct a network that represents a given biological process presents a fundamental challenge in the network science of biology. the quality of network for the organism of interest is critically dependent on the extent of functional annotation of its genome. mostly the automated annotation pipelines do not account for unstructured information present in volumes of literature and hence large fraction of genome remains poorly annotated. however, if used, t ...201323629487
role of mhc class ib molecule, h2-m3 in host immunity against tuberculosis.the mhc class i family comprises both classical (class ia) and non-classical (class ib) members. while the prime function of classical mhc class i molecules (mhc class ia) is to present peptide antigens to pathogen-specific cytotoxic t cells, non-classical mhc-i (mhc class ib) antigens perform diverse array of functions in both innate and adaptive immunity. vaccines against intracellular pathogens such as mycobacterium tuberculosis need to induce strong cellular immune responses. recent studies ...201323628242
[quantitative proteomic analysis of streptomycin resistant and sensitive clinical isolates of mycobacterium tuberculosis].to identify specific antigens related to streptomycin resistant (smr) mycobacterium tuberculosis.201323627108
granulomas of intestinal tuberculosis and crohn's disease can be differentiated by cd73 cell surface marker expression: a pilot study.intestinal tuberculosis (itb) and crohn's disease are similar granulomatous disorders. granulomas are present in both and difficult to differentiate on histopathology alone. a recent study demonstrated recruitment of mesenchymal cells (mscs) at the periphery of granulomas in lymph node tuberculosis which suppressed t cell responses. we hypothesized that granulomas of itb would also recruit mscs to evade host immune response.201323625284
synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme.the present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of c60 with azomethine ylides generated from the corresponding schiff bases of substituted quinazolinone were characterized by elemental analysis, ft-ir, (1)h nmr, (13)c nmr and esi-ms and screened for their antibacterial activity against mycobacterium tuberculosis (h 37 rv s ...201323625031
structural characterization by nmr of a double phosphorylated chimeric peptide vaccine for treatment of alzheimer's disease.rational design of peptide vaccines becomes important for the treatment of some diseases such as alzheimer's disease (ad) and related disorders. in this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the tau protein. the 28-mer linear chimeric peptide consists of the double phosphorylated b cell epitope tau₂₂₉₋₂₃₇[pthr231/pser235] and the ...201323624647
nonlytic fc-fused il-7 synergizes with mtb32 dna vaccine to enhance antigen-specific t cell responses in a therapeutic model of tuberculosis.improvement to the immunogenicity of dna vaccines was evaluated in a mycobacterium tuberculosis (mtb) infection mouse model examining the combined effects of nonlytic fc-fused il-7 dna (il-7-nfc) and flt3-ligand fused mtb32 (f-mtb32) dna. mice were treated with conventional chemotherapy for 6 weeks from 4 weeks after aerosol infection of mtb. following the start of chemotherapy, dna immunizations were administered five times with 2-week intervals. coadministration of il-7-nfc and f-mtb32 dna giv ...201323624092
[emergent strains of rifampicin-resistant mycobacterium tuberculosis complex and susceptibility to isoniazid]. 201523623580
an insight into the regulation of mce4 operon of mycobacterium tuberculosis.the mce4 operon is reported to be involved in cholesterol utilization and intracellular survival of mycobacterium tuberculosis (m. tuberculosis). the regulatory mechanism of this important operon was unknown so far. here we report detection of the promoter region and regulatory factors of the mce4 operon. the in silico analyzed putative promoter region was cloned in promoter selection vector and promoter strength was measured by o-nitrophenyl-β-d-galactopyranosidase (onpg) assay. the transcripti ...201323622789
emergence and spread of extensively and totally drug-resistant tuberculosis, south africa.factors driving the increase in drug-resistant tuberculosis (tb) in the eastern cape province, south africa, are not understood. a convenience sample of 309 drug-susceptible and 342 multidrug-resistant (mdr) tb isolates, collected july 2008-july 2009, were characterized by spoligotyping, dna fingerprinting, insertion site mapping, and targeted dna sequencing. analysis of molecular-based data showed diverse genetic backgrounds among drug-sensitive and mdr tb sensu stricto isolates in contrast to ...201323622714
prioritizing tuberculosis clusters by genotype for public health action, washington, usa.groups of tuberculosis cases with indistinguishable mycobacterium tuberculosis genotypes (clusters) might represent recent transmission. we compared geospatial concentration of genotype clusters with independent priority rankings determined by local public health officials; findings were highly correlated. routine use of geospatial statistics could help health departments identify recent disease transmission.201323621956
diagnostic accuracy of xpert® mtb/rif on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.to determine the diagnostic accuracy of the xpert® mtb/rif assay using samples obtained through bronchoscopy in patients with suspected pulmonary tuberculosis (ptb).201323621953
identification of mycobacterium species in ffpe granulomatous lymphadenitis tissue using reba myco-id®.tuberculous lymphadenitis is the most common form of lymphadenopathy; its main histopathological finding is granulomatous inflammation.201323621948
multidrug-resistant tuberculosis, somalia, 2010-2011.in a nationwide survey in 2011, multidrug-resistant tuberculosis (mdr tb) was found in 5.2% and 40.8% of patients with new and previously treated tb, respectively. these levels of drug resistance are among the highest ever documented in africa and the middle east. this finding presents a serious challenge for tb control in somalia.201323621911
[a predisposing clinical condition for disseminated tuberculosis: hairy cell leukemia].hairy cell leukemia (hcl), a rare and slow-progressive b-cell lymphoproliferative disease, enhances predisposition to infectious complications, especially to disseminated mycobacterial infections. although the association between hcl and mycobacterial disease has been established, disseminated mycobacterium tuberculosis infection has been reported only in a few case series. in this report, a disseminated tuberculosis (tb) case who had been diagnosed as hcl with histopathologic examination of the ...201323621735
[determination of the cytokine gene polymorphism and genetic susceptibility in tuberculosis patients].tuberculosis (tb) is a complicated disease in which biological, socioeconomical and environmental factors play role. since only 10% of the individuals infected with mycobacterium tuberculosis develop active disease, it has been suggested that host genetic factors may influence the risk for the development of tb. in this study, we aimed to investigate the presence and role of single nucleotide polymorphisms in the gene regions responsible for cytokine production, since these factors are considere ...201323621725
substrate and reaction specificity of mycobacterium tuberculosis cytochrome p450 cyp121: insights from biochemical studies and crystal structures.cytochrome p450 cyp121 is essential for the viability of mycobacterium tuberculosis. studies in vitro show that it can use the cyclodipeptide cyclo(l-tyr-l-tyr) (cyy) as a substrate. we report an investigation of the substrate and reaction specificities of cyp121 involving analysis of the interaction between cyp121 and 14 cyy analogues with various modifications of the side chains or the diketopiperazine (dkp) ring. spectral titration experiments show that cyp121 significantly bound only cyclodi ...201323620594
autophagy as an innate defense against mycobacteria.over the past several years, much has been revealed about the roles of autophagy and the mechanisms by which the autophagic pathway activates the host innate effector response against mycobacterium tuberculosis (mtb) infection. in response to invading mycobacteria, the host innate immune system not only recognizes pathogen motifs through innate receptors, it also produces appropriate effector proteins, including cytokines. these innate signals activate or regulate autophagic pathways during infe ...201323620156
genetic variants of marco are associated with susceptibility to pulmonary tuberculosis in a gambian population.the two major class a scavenger receptors are scavenger receptor a (sra), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (marco), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. although the primary role of sra appears to be clearance of modified host proteins and lipids, mice defective i ...201323617307
is6110 restriction fragment length polymorphism typing of drug-resistant mycobacterium tuberculosis strains from northeast south africa.tuberculosis (tb) remains a deadly infectious disease affecting millions of people worldwide; 95% of tb cases, with 98% of death occur in developing countries. the situation in south africa merits special attention. a total of 21,913 sputum specimens of suspected tb patients from three provinces of south africa routinely submitted to the tb laboratory of dr. george mukhari (dgm) hospital were assayed for mycobacterium tuberculosis (mtb) growth and antibiotic susceptibility. the genetic diversity ...201323617199
evaluation of cobas taqman mtb for direct detection of the mycobacterium tuberculosis complex in comparison with cobas amplicor mtb.the roche cobas amplicor mtb assay, recently replaced by the roche cobas taqman mtb assay, was one of the first commercially available assays for detection of the mycobacterium tuberculosis complex based on nucleic acid amplification. we reported previously on the limited specificity of the cobas amplicor mtb assay, in particular for positive samples with an optical density at 660 nm (od660) of <2.0. using a selected set of respiratory samples, which were scored as false positive by the cobas am ...201323616457
integrating the xpert mtb/rif assay into a diagnostic workflow for rapid detection of mycobacterium tuberculosis in a low-prevalence area.the xpert mtb/rif assay is a rapid and fully automated real-time pcr assay. the performance of the xpert mtb/rif assay as a primary screening test for urgent clinical specimens was evaluated during a 2-year period. the results showed that replacing smear microscopy with the xpert mtb/rif assay facilitates laboratory handling and improves the sensitivity and specificity of mycobacterium tuberculosis detection.201323616455
analysis of mutations in streptomycin-resistant strains reveals a simple and reliable genetic marker for identification of the mycobacterium tuberculosis beijing genotype.the mycobacterium tuberculosis pandemic is a major health problem, further complicated by an increasing incidence of drug-resistant isolates and the existence of highly transmissible strains, such as those in the beijing family. streptomycin (str)-resistant m. tuberculosis clinical isolates have been analyzed to look for mutations in the rpsl, rrs, and gidb genes. in addition, the rv1258c gene, which encodes tap, an efflux pump that transports str, has been sequenced. mutations affecting codons ...201323616454
unravelling the gordian knot: diagnostic dilemma in an hiv-positive patient with neurological involvement.we report a case of a 40-year-old seropositive-hiv patient with a cd4 count of 120 who presented with fever, severe headache and neck stiffness. suspecting a case of tubercular meningitis (tbm; as tuberculosis is the commonest opportunistic infection in hiv/aids patients in india), a lumbar puncture was performed and a cerebrospinal fluid study revealed tbm. the patient was started on combination antitubercular drug therapy from directly observed treatment, short course (dots) (cat 1 regimen) al ...201323616316
crystal structure of mycobacterium tuberculosis polyketide synthase 11 (pks11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.pks11 is one of three type iii polyketide synthases (pkss) identified in mycobacterium tuberculosis. although many pkss in m. tuberculosis have been implicated in producing complex cell wall glycolipids, the biological function of pks11 is unknown. pks11 has previously been proposed to synthesize alkylpyrones from fatty acid substrates. we solved the crystal structure of m. tuberculosis pks11 and found the overall fold to be similar to other type iii pkss. pks11 has a deep hydrophobic tunnel pro ...201323615910
mycobacterium tuberculosis-induced expression of granulocyte-macrophage colony stimulating factor is mediated by pi3-k/mek1/p38 mapk signaling pathway.members of the colony stimulating factor cytokine family play important roles in macrophage activation and recruitment to inflammatory lesions. among them, granulocyte-macrophage colony stimulating factor (gm-csf) is known to be associated with immune response to mycobacterial infection. however, the mechanism through which mycobacterium tuberculosis (mtb) affects the expression of gm-csf is poorly understood. using pma-differentiated thp-1 cells, we found that mtb infection increased gm-csf mrn ...201323615263
fitness of acquired drug resistant mycobacterium tuberculosis isolates from dots compliant patients.the increasing levels of multi drug resistant tuberculosis (mdrtb) in endemic regions are a cause of concern. when mdr strains exhibit higher fitness they threaten global tuberculosis control. evaluation of factors other than the particular non-synonymous substitutions that contribute to the fitness of strains may have an important bearing on understanding the spread of the disease. the aim of the study was to determine the fitness of mdrtb strains from tb endemic region, acquiring drug resistan ...201323615069
characterization of an aldolase-dehydrogenase complex from the cholesterol degradation pathway of mycobacterium tuberculosis.hsaf and hsag are an aldolase and dehydrogenase from the cholesterol degradation pathway of mycobacterium tuberculosis. hsaf could be heterologously expressed and purified as a soluble dimer, but the enzyme was inactive in the absence of hsag. hsaf catalyzes the aldol cleavage of 4-hydroxy-2-oxoacids to produce pyruvate and an aldehyde. the enzyme requires divalent metals for activity, with a preference for mn(2+). the km values for 4-hydroxy-2-oxoacids were about 20-fold lower than observed for ...201323614353
synthesis and discovery of new bisadducts derived from heterocyclic aldehydes and active methylene compounds as potent antitubercular agents.a series of some new bisadducts possessing five, six membered and coumarin subunits were synthesized by the condensation of heterocyclic aldehydes with active methylene compounds and characterized by ir, nmr and x-ray crystallographic studies and were assayed as antitubercular agents. among the bisadducts, 4-hydroxy-3-[(4-hydroxy-2-oxo-2h-3-chromenyl)(3-thienyl)methyl]-2h-2-chromenone 3a was found to be the most promising compound, active against mycobacterium tuberculosis (mtb) h37rv and isonia ...201323614277
preventive vaccines for tuberculosis.there are nearly ten million new cases and 1.4 million deaths from tuberculosis (tb) each year, and the 90-year old bacille calmette-guérin (bcg) vaccine in widespread use appears to have minimal impact on the worldwide incidence, despite demonstrating reasonable efficacy against complications of infant tb and death. novel vaccine development has accelerated in the past ten years, with at least 16 candidates entering human trials, and a few vaccines have entered into phase 2b efficacy studies. h ...201323598486
decreased expression of mir-21, mir-26a, mir-29a, and mir-142-3p in cd4⁺ t cells and peripheral blood from tuberculosis patients.the vast majority of mycobacterium tuberculosis (m. tuberculosis) infected individuals are protected from developing tuberculosis and t cells are centrally involved in this process. micrornas (mirna) regulate t-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in m. tuberculosis infection. we determined the expression profile of 29 selected mirnas in cd4(+) t cells from tuberculosis patients and contacts with latent m. tuberculosis infection (ltbi). the ...201323613882
magnetic barcode assay for genetic detection of pathogens.the task of rapidly identifying patients infected with mycobacterium tuberculosis in resource-constrained environments remains a challenge. a sensitive and robust platform that does not require bacterial isolation or culture is critical in making informed diagnostic and therapeutic decisions. here we introduce a platform for the detection of nucleic acids based on a magnetic barcoding strategy. pcr-amplified mycobacterial genes are sequence-specifically captured on microspheres, labelled by magn ...201323612293
preliminary structure-activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant mycobacterium tuberculosis strains.tuberculosis (tb) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent tb. this is further aggravated by hiv coinfection and the emergence of multidrug- and extensively drug-resistant (mdr and xdr, respectively) tb; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. we report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent ...201323611124
immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production.immunoresponsive gene 1 (irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. here, we identify irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. using a gain-and-loss-of-function approach in both mouse and human immune cells, we found irg1 expression levels correlating with the amount ...201323610393
anti-mycobacterial screening of five indian medicinal plants and partial purification of active extracts of cassia sophera and urtica dioica.to find out the anti-mycobacterial potential of cassia sophera (c. sophera), urtica dioica (u. dioica), momordica dioica, tribulus terrestris and coccinia indica plants against multi-drug resistant (mdr) strain of mycobacterium tuberculosis (m. tuberculosis).201323608375
[pericardial tuberculosis is still an important differential diagnosis in denmark].we report a case where tuberculous pericarditis was diagnosed in a 46-year-old man with turkish background. the patient had typical symptoms of tuberculosis in the form of chest pain, cough and breathlessness and systemic symptoms such as fever, weight loss and fatigue. an echocardiography showed pericardial effusion, and diagnosis was confirmed by culture of mycobacterium tuberculosis from gastric aspirate and lymph node biopsy. since there is an efficient cure for this potentially deathly infe ...201323608014
genotyping and drug resistance patterns of mycobacterium tuberculosis strains observed in a tuberculosis high-burden municipality in northeast, brazil.this study has used a combination of clinical information, spoligotyping, and georeferencing system to elucidate the genetic diversity of the mycobacterium tuberculosis isolates circulating in a tb-prevalent municipality of northeast brazil.201323607922
evaluation of mgit 960 system for the second-line drugs susceptibility testing of mycobacterium tuberculosis.many laboratories validate dst of the second-line drugs by bactec mgit 960 system. the objective of this study is to evaluate the critical concentration and perform dst for the 2nd line drugs. we evaluated 193 clinical strains of m. tuberculosis isolated from patients in south korea. testing the critical concentration of six second-line drugs was performed by mgit 960 and compared with l-j proportion method. the critical concentration was determined to establish the most one that gave the differ ...201323606961
a mycobacteriophage-derived trehalose-6,6'-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities.bacteriophages, the viruses of eubacteria, have developed unique mechanisms to interact with their host bacteria. they have been viewed as potential antibacterial therapeutics. mycobacteriophage-derived compounds may interact with mycobacterium tuberculosis (mtb) and/or its components, such as the cord factor, trehalose-6,6'-dimycolate (tdm), which is the most abundant glycolipid produced on the surface of mtb. tdm emulsion injected intravenously into mice induces lung immunopathology that mimic ...201323603838
genotypes of mycobacterium tuberculosis in patients at risk of drug resistance in bolivia.bolivia ranks among the 10 latin american countries with the highest rates of tuberculosis (tb) and multidrug resistant (mdr) tb. in view of this, and of the lacking information on the population structure of mycobacterium tuberculosis in the country, we explored genotype associations with drug resistance and clustering by analyzing isolates collected in 2010 from 100 consecutive tb patients at risk of drug resistance in seven of the nine departments in which bolivia is divided. fourteen isolate ...201323603419
thiol modified mycolic acids.patient serum antibodies to mycolic acids have the potential to be surrogate markers of active tuberculosis (tb) when they can be distinguished from the ubiquitously present cross-reactive antibodies to cholesterol. mycolic acids are known to interact more strongly with antibodies present in the serum of patients with active tb than in patients with latent tb or no tb. examples of single stereoisomers of mycolic acids with chain lengths corresponding to major homologues of those present in mycob ...201323603063
the underling mechanism of bacterial tetr/acrr family transcriptional repressors.bacteria transcriptional regulators are classified by their functional and sequence similarities. member of the tetr/acrr family is two-domain proteins including an n-terminal hth dna-binding motif and a c-terminal ligand recognition domain. the c-terminal ligand recognition domain can recognize the very same compounds as their target transporters transferred. tetrs act as chemical sensors to monitor both the cellular environmental dynamics and their regulated genes underlying many events, such ...201323602932
tuberculosis diagnosis using immunodominant, secreted antigens of mycobacterium tuberculosis.tuberculosis (tb) remains a major public health concern in most low-income countries. hence, rapid and sensitive tb diagnostics play an important role in detecting and preventing the disease. in addition to established diagnostic methods, several new approaches have been reported. some techniques are simple but time-consuming, while others require complex instrumentation. one prominent and readily available approach is to detect proteins that mycobacterium tuberculosis secretes, such as mpt64, t ...201323602700
sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite.tuberculosis (tb), is caused by the bacteria, mycobacterium tuberculosis and its a threat to humans since centuries. depending on the type of tb, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. many adverse effects are associated with the currently available tb medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.develop ...201323601852
erythropoietin-producing tubercle granuloma in a hemodialysis patient.we describe a case of a fever of unknown etiology that was caused by a caseating tubercle granuloma which produced erythropoietin. to our knowledge, this is the first report of an erythropoietin- producing granuloma.201323601138
heme degradation by staphylococcus aureus isdg and isdi liberates formaldehyde rather than carbon monoxide.isdg and isdi from staphylococcus aureus are novel heme-degrading enzymes containing unusually nonplanar (ruffled) heme. while canonical heme-degrading enzymes, heme oxygenases, catalyze heme degradation coupled with the release of co, in this study we demonstrate that the primary c1 product of the s. aureus enzymes is formaldehyde. this finding clearly reveals that both isdg and isdi degrade heme by an unusual mechanism distinct from the well-characterized heme oxygenase mechanism as recently p ...201323600533
two cases of lupus vulgaris in childhood and review of the clinical challenges.lupus vulgaris (lv) is the most common form of cutaneous tuberculosis (tb) in europe, nevertheless the overall incidence is low. it constitutes about 1.5% of all extra-pulmonary cases worldwide. a slight raise in tb incidence rates among children was recently registered in germany, which can be explained by the increased immigration.201423599230
simple multiplex pcr assay for identification of beijing family mycobacterium tuberculosis isolates with a lineage-specific mutation in rv0679c.the beijing genotype of mycobacterium tuberculosis is known to be a worldwide epidemic clade. it is suggested to be a possibly resistant clone against bcg vaccination and is also suggested to be highly pathogenic and prone to becoming drug resistant. thus, monitoring the prevalence of this lineage seems to be important for the proper control of tuberculosis. the rv0679c protein of m. tuberculosis has been predicted to be one of the outer membrane proteins and is suggested to contribute to host c ...201323596248
viability of mycobacterium tuberculosis after processing with commercial nucleic acid extraction kits. 201323596233
thrombocytosis is associated with mycobacterium tuberculosis infection and positive acid-fast stains in granulomas.mycobacterium tuberculosis infection is associated with thrombocytosis. we sought to determine if this information might be valuable in evaluating granulomas using acid-fast stains (afs). fifty-eight patients with culture-confirmed m tuberculosis infection were compared with 75 patients with atypical mycobacterial infection and 48 patients negative for mycobacteria. thrombocytosis (platelet count >360 × 10(3)/μl [360 × 10(9)/l]) was significantly more common in patients with m tuberculosis (50%) ...201323596109
the search for a genetic factor associating with immune restoration disease in hiv patients co-infected with mycobacterium tuberculosis.up to 43% of hiv-infected patients co-infected with mycobacterium tuberculosis experience exacerbations of tuberculosis (tb) after commencing antiretroviral therapy (art). these are termed immune restoration disease (ird). it is unclear why individual susceptibility varies.201323594560
detecting human bacterial pathogens in wastewater treatment plants by a high-throughput shotgun sequencing technique.human pathogens are one of the major threats to global public health. wastewater treatment plants (wwtps) serve as city guts to receive and digest various human pathogens. several techniques have been developed to detect human pathogens in wwtps and to assess potential environmental risks. in this study, we employed 24 metagenomic dna data sets derived from a high-throughput shotgun sequencing technique to more accurately and efficiently detect human bacterial pathogens in influent, activated sl ...201323594284
contribution of moxifloxacin or levofloxacin in second-line regimens with or without continuation of pyrazinamide in murine tuberculosis.high-dose levofloxacin (l) (1,000 mg) was as active as moxifloxacin (m) (400 mg) in an early bactericidal activity trial, suggesting these fluoroquinolones could be used interchangeably. whether pyrazinamide (z) contributes sterilizing activity beyond the first 2 months in fluoroquinolone-containing second-line regimens remains unknown.201323593945
expression of tnf-alpha-dependent apoptosis-related genes in the peripheral blood of malagasy subjects with tuberculosis.the majority of mycobacterium tuberculosis (mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. however, the constituents of the effective "protective immunity" against tuberculosis responsible for containing most infections remain unknown. evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. it is clear that apoptosis plays a role in the control of tuberculos ...201323593415
a dual read-out assay to evaluate the potency of compounds active against mycobacterium tuberculosis.tuberculosis is a serious global health problem caused by the bacterium mycobacterium tuberculosis. there is an urgent need for discovery and development of new treatments, but this can only be accomplished through rapid and reproducible m. tuberculosis assays designed to identify potent inhibitors. we developed an automated 96-well assay utilizing a recombinant strain of m. tuberculosis expressing a far-red fluorescent reporter to determine the activity of novel compounds; this allowed us to me ...201323593234
mycobacterium tuberculosis responds to chloride and ph as synergistic cues to the immune status of its host cell.the ability of mycobacterium tuberculosis (mtb) to thrive in its phagosomal niche is critical for its establishment of a chronic infection. this requires that mtb senses and responds to intraphagosomal signals such as ph. we hypothesized that mtb would respond to additional intraphagosomal factors that correlate with maturation. here, we demonstrate that [cl⁻] and ph correlate inversely with phagosome maturation, and identify cl⁻ as a novel environmental cue for mtb. mtb responds to cl⁻ and ph s ...201323592993
primary gastric tuberculosis mimicking gastric cancer: a case report.gastric tuberculosis is an uncommon manifestation of extra-pulmonary tuberculosis infection. the clinical signs of this type of infection are nonspecific and misleading. clinically gastric tuberculosis resembles peptic ulcer disease or malignancy. we report a case of gastric tuberculosis, which was treated as acid peptic disease, in an iranian immunocompetent adult with no pulmonary tuberculosis, who received surgery for gastric cancer. diagnosis was based on pcr despite the detection of negativ ...201323592646
direct molecular detection of mycobacterium tuberculosis suspected to be the specific infection in a case of recurrent tonsillitis.we report a case of a 21-year-old man with recurrent tonsillitis caused by mycobacterium tuberculosis. for a period of 5 months, the patient had tonsillitis seven times and was treated with several oral or parenteral antibiotics. on one of these occasions, tonsillitis was complicated with a peritonsillar abscess that was treated by incision. according to relevant bibliographic data, this is the first case of mycobacterium tuberculosis confirmed by direct molecular microbiology methods from the t ...201323591525
oral intake of phenylbutyrate with or without vitamin d3 upregulates the cathelicidin ll-37 in human macrophages: a dose finding study for treatment of tuberculosis.we earlier showed that 4-phenylbutyrate (pb) can induce cathelicidin ll-37 expression synergistically with 1,25-dihydroxyvitamin d3 in a lung epithelial cell line. we aimed to evaluate a therapeutic dose of pb alone or in combination with vitamin d3 for induction of ll-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (mdm).201323590701
stop antibiotics on guidance of procalcitonin study (saps): a randomised prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients--calculated sample size: 1816 patients.unnecessary long-term use of broad-spectrum antibiotics is linked to the emergence and selection of resistant bacteria, prolonged hospitalisation and increased costs. several clinical trials indicate that the biomarker procalcitonin (pct) can guide antibiotic therapy. some of these trials have shown a promising reduction in the number of antibiotic prescriptions, duration of antibiotic therapy and even length of stay in the icu, although their size and selection criteria limit their external val ...201323590389
regulatory t cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis.there are hardly any data about the frequency of cd4(+)cd25(+)foxp3(+) regulatory t cells (t-regs) in the lungs of patients with active tuberculosis (tb).201323590266
revision of tuberculous lesions in the bácsalmás-oalmás series--preliminary morphological and biomolecular studies.previous investigations carried out in some parts of the 16th-17th century ad series of bácsalmás-oalmás (southern hungary) have already provided interesting paleopathological cases of tuberculosis (e.g. molnár & pálfi 1994). these studies were essentially based on macromorphological analysis, biomolecular methods were used only in a few cases (e.g. haas et al. 2000). from a macromorphological point of view, former investigations have only considered 'classical' tuberculosis (tb) alterations (ad ...201323590114
poor prognostic significance of mycobacterium tuberculosis infection during bortezomib-containing chemotherapy in patients with multiple myeloma.bortezomib administration leads to a transient decrease in cd4(+) t cells, increasing the susceptibility to opportunistic infections. the activation and proliferation of cd4(+) t cells are particularly important in the host's defense against tuberculosis infection. the aim of this study was to determine the incidence and clinical significance of tuberculosis infection in patients with multiple myeloma (mm) treated with a bortezomib-containing regimen.201323589793
crystal structure of l,d-transpeptidase ldtmt2 in complex with meropenem reveals the mechanism of carbapenem against mycobacterium tuberculosis. 201323588382
ivermectin lacks antituberculous activity. 201323587653
polyphosphate deficiency in mycobacterium tuberculosis is associated with enhanced drug susceptibility and impaired growth in guinea pigs.inorganic polyphosphate (polyp), a linear polymer of hundreds of phosphate residues linked by atp-like phosphoanhydride bonds, is found in all organisms and performs a wide variety of functions. this study shows that polyp accumulation occurs in mycobacterium tuberculosis upon exposure to various stress conditions. m. tuberculosis possesses a single homolog of ppk-1, and we have disrupted ppk-1 in the m. tuberculosis genome by allelic replacement. the mutant strain exhibited negligible levels of ...201323585537
[role of phospholipase c in cytoskeleton rearrangements of dendritic cells invaded by mycobacterium tuberculosis].to investigate the role of phospholipase c(plc) in cytoskeleton rearrangement of mouse dendritic cells invaded by mycobacterium tuberculosis.201323585005
mass spectrometry based lipid(ome) analyzer and molecular platform: a new software to interpret and analyze electrospray and/or matrix-assisted laser desorption/ionization mass spectrometric data of lipids: a case study from mycobacterium tuberculosis.mass spectrometry based lipid(ome) analyzer and molecular platform (ms-lamp) is a new software capable of aiding in interpreting electrospray ionization (esi) and/or matrix-assisted laser desorption/ionization (maldi) mass spectrometric data of lipids. the graphical user interface (gui) of this standalone programme is built using perl::tk. two databases have been developed and constituted within ms-lamp, on the basis of mycobacterium tuberculosis (m. tb) lipid database (www.mrl.colostate.edu) an ...201323584940
implication of purinergic p2x7 receptor in m. tuberculosis infection and host interaction mechanisms: a mouse model study.in the present study, we analyzed the role of purinergic p2x7 receptor in mycobacterium tuberculosis infection and host interaction mechanisms in vitro and in vivo. for experimental procedures, a macrophage murine cell line raw 264.7, and male swiss, wild-type c57bl/6 and p2x7 receptor knockout (p2x7r−/−) mice were used throughout this study. we have demonstrated that treatment of raw 264.7 cells with atp (3 and 5 mm) resulted in a statistically significant reduction of m. tuberculosis-colony-fo ...201323583008
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