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[immunological characteristics of mycobacterium tuberculosis antigen rv2628].antigen rv2628 of mycobacterium tuberculosis is associated with latent tuberculosis infection. in this study, rv2628 was prokaryotic expressed and purified, its immunological characteristics was evaluated with macrophage cell line raw264.7 and balb/c mice. the results show that rv2628 was mainly expressed in form of inclusion body confirmed by sds-page, and could react with rabbit anti-h37rv polyclonal antibody detected by western blotting assay, indicating that the protein had an effective immu ...201424941746
getting personal perspectives on individualized treatment duration in multidrug-resistant and extensively drug-resistant tuberculosis.tuberculosis (tb) differs from most other bacterial infectious diseases by a very long duration of combination antibiotic therapy required to achieve relapse-free cure. although the standard recommended "short-course" treatment length for tb is 6 months, the world health organization recommends a duration of 20 months for the treatment of patients with multidrug-resistant and extensively drug-resistant tb (m/xdr-tb). apart from the long duration of anti-tb therapy, treatment of m/xdr-tb is very ...201424941306
ofloxacin resistance in mycobacterium tuberculosis is associated with efflux pump activity independent of resistance pattern and genotype.drug-resistance to ofloxacin (ofx) in mycobacterium tuberculosis is due to missense mutations in gyra and other factors, such as alterations in the activity of drug efflux pumps. in this study, we identified 8 extensively drug resistant tuberculosis (xdr-tb), 40 multidrug resistant tb (mdr-tb), 38 polydrug resistant tb (pdr-tb), and 16 single ofx-resistant tb from 102 clinical isolates. we tested the effect of three efflux inhibitors, reserpine, verapamil, and carbonyl cyanide m-chlorophenyl hyd ...201424940805
comparative genomics of mycobacterium tuberculosis drug efflux pumps and their transcriptional regulators.efflux pump systems are important in general drug resistance. understanding efflux pumps can inform drug target selection and novel antibiotics designs. in this review, we have summarized the physiological roles, types, and mechanisms of drug efflux pumps. mycobacterium tuberculosis is the causative agent of tuberculosis, a global threat to public health, and the increasing resistance of this mycobacterium to antibiotics is alarming. therefore, we have focused on the comparative genomics of effl ...201424940769
orbital and adnexal tuberculosis: a case series from a south indian population.orbital tuberculosis (otb) is rare and may be regarded as a manifestation of extrapulmonary tuberculosis. we report an interesting case series of six patients with varied presentations of orbital and adnexal tuberculosis in a south indian patient population.201424940452
biosynthesis of a water-soluble lipid i analogue and a convenient assay for translocase i.translocase i (mray/murx) is an essential enzyme in growth of the vast majority of bacteria that catalyzes the transformation from udp-murnac-pentapeptide (park's nucleotide) to prenyl-murnac-pentapeptide (lipid i), the first membrane-anchored peptidoglycan precursor. murx has received considerable attention in the development of new tuberculosis (tb) drugs due to the fact that the murx inhibitors kill exponentially growing mycobacterium tuberculosis (mtb) much faster than clinically used tb dru ...201424939461
the dosr dormancy regulator of mycobacterium tuberculosis stimulates the na(+)/k (+) and ca (2+) atpase activities in plasma membrane vesicles of mycobacteria.the latency global regulator dosr regulon of mycobacterium tuberculosis, which is stimulated by hypoxia, comprises approximately fifty genes including ctpf (rv1997), which encodes a putative alkali/alkaline earth ion transporter of the plasma membrane. in this work, the influence of hypoxia and m. tuberculosis dosr on the atpase activity of mycobacterial plasma membrane was assessed. we performed bioinformatic analyses which indicated that the pma1 gene product is the m. smegmatis ortholog of th ...201424939385
assessment of children exposed to adult pulmonary tuberculosis in cali, colombia.there is a lack of uniform criteria for the diagnosis and management of tuberculosis (tb) in children in cali, colombia. addressing tb in children is a challenge in this setting, under both programmatic and research conditions.201424939365
3-benzylidene-4-chromanones: a novel cluster of anti-tubercular agents.in a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a-l were evaluated for growth inhibition of mycobacterium tuberculosis h37rv. three promising compounds 1d, g, j emerged as the lead compounds with the ic50 and ic90 values of less than 1 µg/ml. evaluation of the potent compounds 1d, g, j and k against vero monkey kidney cells revealed that these compounds are far more toxic to m. tuberculosis than to vero cells. structure-activity relationships demo ...201524939095
igg, igm and iga antibodies against the novel polyprotein in active tuberculosis.the present study was aimed to evaluate whether igg, igm and iga antibodies levels detected against a novel mycobacterium tuberculosis polyprotein 38 f-64 f (with 38 f being the abbreviation for 38kd-esat6-cfp10 and 64 f for mtb8.4-mpt64-tb16.3-mtb8) are suitable for diagnosing active tuberculosis, and for monitoring the efficacy of chemotherapy on tb patients.201424939009
insights into battles between mycobacterium tuberculosis and macrophages.as the first line of immune defense for mycobacterium tuberculosis (mtb), macrophages also provide a major habitat for mtb to reside in the host for years. the battles between mtb and macrophages have been constant since ancient times. triggered upon mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. toll-like receptors (tlrs) expressed on macrophages can r ...201424938416
screening for streptomycin resistance-conferring mutations in mycobacterium tuberculosis clinical isolates from poland.currently, mutations in three genes, namely rrs, rpsl, and gidb, encoding 16s rrna, ribosomal protein s12, and 16s rrna-specific methyltransferase, respectively, are considered to be involved in conferring resistance to streptomycin (str) in mycobacterium tuberculosis. the aim of this study was to investigate the spectrum and frequency of these mutations in m. tuberculosis clinical isolates, both resistant and susceptible to str. sixty-four m. tuberculosis isolates recovered from as many tb pati ...201424937123
cytotoxic coumarins from toddalia asiatica.three new coumarins and 13 known compounds were isolated from the stem bark of toddalia asiatica. compounds 1, 3, 8, and 9 showed cytotoxicity against the nci-h187 cell line with ic50 values ranging from 6 to 9 µg/ml. compounds 4 and 9 exhibited cytotoxicity against the mcf-7 cell line with ic50 values of 3.17 and 9.79 µg/ml, respectively. compound 9 also displayed cytotoxic activity against kb cells with an ic50 value of 8.63 µg/ml. in addition, compound 14 showed antimalarial activity against ...201424936959
human type 5 adenovirus-based tuberculosis vaccine: is the respiratory route of delivery the future?despite progress in managing tb, there were 8.6 million new cases in 2012. to control tb will require a more effective vaccine than bcg, new drugs and better diagnostic tests. recombinant replication-defective adenoviruses expressing foreign dna have been studied as vaccines. we developed and evaluated a recombinant replication-deficient human ad5 vector expressing ag85a (ad5ag85a) as a tb vaccine in animal models and a phase i human study. animal models of ad5ag85a show markedly improved protec ...201424935214
elucidating the structural basis of diphenyl ether derivatives as highly potent enoyl-acp reductase inhibitors through molecular dynamics simulations and 3d-qsar study.diphenyl ether derivatives are good candidates for anti-tuberculosis agents that display a promising potency for inhibition of inha, an essential enoyl-acyl carrier protein (acp) reductase involved in fatty acid biosynthesis pathways in mycobacterium tuberculosis. in this work, key structural features for the inhibition were identified by 3d-qsar comsia models, constructed based on available experimental binding properties of diphenyl ether inhibitors, and a set of four representative compounds ...201424935113
molecular analysis of the rpsl gene for rapid detection of streptomycin-resistant mycobacterium tuberculosis: a meta-analysis.drug-resistant mycobacterium tuberculosis (mtb) is a major threat to tuberculosis (tb) control programs and public health. most conventional methods of drug susceptibility testing (dst) are precise but time-consuming. molecular analysis of the rpsl gene has been used widely in diagnosing streptomycin-resistant mtb since it is rapid and specific. the aim of the present study was to perform a meta-analysis to assess the accuracy of molecular assay of the rpsl gene for the rapid detection of strept ...201424934990
prosthesis infection by mycobacterium tuberculosis in a patient with rheumatoid arthritis: a case report and literature review. 201424932907
[childhood tuberculosis].childhood tb is an indication of failing tb control in the community. it allows disease persistence in the population. mortality and morbidity due to tb is high in children. moreover, hiv co-infection and multidrug-resistant diseases are as frequent in children as in adults. infection is more frequent in younger children. disease risk after primary infection is greatest in infants younger than 2 years. in case of exposure, evidence of infection can be obtained using the tuberculin skin test (tst ...201524932504
diagnostic performance of the xpert mtb/rif assay for tuberculous lymphadenitis on fine needle aspirates from ethiopia.the xpert mtb/rif (xpert) test is a novel automated molecular diagnostic recently endorsed by the world health organization for rapid diagnosis of tuberculosis (tb). nevertheless, performance related data from high tb prevalence regions to investigate clinically suspected tb lymphadenitis are limited. to evaluate the performance of xpert test for direct detection of the mycobacterium tuberculosis complex (mtbc) and rifampicin (rif) resistance in lymph node aspirates, a cross-sectional study was ...201424931451
tuberculous botryomycosis of the hand: case report.we report a case of a 17-year-old boy who presented with botryoid lesions of both hands. these lesions resembled those of cutaneous botryomycosis. we treated him with surgical debridement and were unable to isolate infective agents initially. however, 3 months later mycobacterium tuberculosis grew in the culture. one year of antituberculous drug therapy resulted in healing of the lesions.201424928358
acid-fast bacilli culture positivity and drug resistance in abdominal tuberculosis in mumbai, india.culture positivity for mycobacterium tuberculosis complex (mtb) in abdominal tuberculosis (tb) using lowenstein jensen medium and bactec system varies from 25 % to 36 %. data on the prevalence of drug resistance in primary abdominal tb is scant. our aim was to study the acid-fast bacilli (afb) culture positivity rate in primary abdominal tb using bactec mycobacterial growth indicator tubes (mgit) system and the prevalence of drug resistance in these patients.201424927950
mycobacterium tuberculosis supports protein tyrosine phosphorylation.reversible protein phosphorylation determines growth and adaptive decisions in mycobacterium tuberculosis (mtb). at least 11 two-component systems and 11 ser/thr protein kinases (stpks) mediate phosphorylation on asp, his, ser, and thr. in contrast, protein phosphorylation on tyr has not been described previously in mtb. here, using a combination of phospho-enrichment and highly sensitive mass spectrometry, we show extensive protein tyr phosphorylation of diverse mtb proteins, including stpks. s ...201424927537
1-substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1h-tetrazoles and their isosteric analogs: a new class of selective antitubercular agents active against drug-susceptible and multidrug-resistant mycobacteria.in this work, a new class of highly potent antituberculosis agents, 1-substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1h-tetrazoles and their oxa and selanyl analogs, is described. the minimal inhibitory concentration (mic) values reached 1 μm (0.36-0.44 μg/ml) against mycobacterium tuberculosis cnctc my 331/88 and 0.25-1 μm against six multidrug-resistant clinically isolated strains of m. tuberculosis. the antimycobacterial effects of these compounds were highly specific because they were ineffecti ...201424927053
safety assessment in primary mycobacterium tuberculosis smear microscopy centres in blantyre malawi: a facility based cross sectional survey.tuberculosis (tb) is caused by mycobacterium tuberculosis and is transmitted mainly through aerosolization of infected sputum which puts laboratory workers at risk in spite of the laboratory workers' risk of infection being at 3 to 9 times higher than the general public. laboratory safety should therefore be prioritized and optimized to provide sufficient safety to laboratory workers.201324926396
[utility value of a t-cell interferon-γ release assay based on recombinant mycobacterium tuberculosis 11kd protein in the diagnosis of tuberculosis].to evaluate the diagnostic efficiency of a t-cell interferon-γ release assay based on recombinant mycobacterium tuberculosis (mtb) 11kd protein for diagnosing tuberculosis.201424924715
comparative genomic analysis of mycobacterium tuberculosis clinical isolates.due to excessive antibiotic use, drug-resistant mycobacterium tuberculosis has become a serious public health threat and a major obstacle to disease control in many countries. to better understand the evolution of drug-resistant m. tuberculosis strains, we performed whole genome sequencing for 7 m. tuberculosis clinical isolates with different antibiotic resistance profiles and conducted comparative genomic analysis of gene variations among them.201424923884
cell-to-cell transfer of m. tuberculosis antigens optimizes cd4 t cell priming.during mycobacterium tuberculosis and other respiratory infections, optimal t cell activation requires pathogen transport from the lung to a local draining lymph node (ln). however, the infected inflammatory monocyte-derived dendritic cells (dcs) that transport m. tuberculosis to the local lymph node are relatively inefficient at activating cd4 t cells, possibly due to bacterial inhibition of antigen presentation. we found that infected migratory dcs release m. tuberculosis antigens as soluble, ...201424922576
tuberculosis drug discovery and emerging targets.current tuberculosis (tb) therapies take too long and the regimens are complex and subject to adverse effects and drug-drug interactions with concomitant medications. the emergence of drug-resistant tb strains exacerbates the situation. drug discovery for tb has resurged in recent years, generating compounds (hits) with varying potential for progression into developable leads. in parallel, advances have been made in understanding tb pathogenesis. it is now possible to apply the lessons learned f ...201424920100
analysis of cases with tuberculous peritonitis: a single-center experience.tuberculous peritonitis (tp) is a rare form of tuberculosis and is caused by peritoneal involvement with mycobacterium tuberculosis. a distinctive correlation exists between socioeconomic state and disease prevalence. we aimed to evaluate the clinical, laboratory, and radiological findings of patients with tp.201424918135
epitope-specific antibody levels in tuberculosis: biomarkers of protection, disease, and response to treatment.monoclonal antibodies restricted to mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. antibody to the immunodominant epitopes was associated with hla-dr15. occupational exposure showed a different response and was consistent with recognition of dormancy-related proteins and protection despite exposure to tuberculosis (tb). studies in leprosy re ...201424917863
frequency of mutations in the rpob gene of multidrug-resistant mycobacterium tuberculosis clinical isolates from sudan. 201424916882
targeting mycobacterium tuberculosis nucleoid-associated protein hu with structure-based inhibitors.the nucleoid-associated protein hu plays an important role in maintenance of chromosomal architecture and in global regulation of dna transactions in bacteria. although hu is essential for growth in mycobacterium tuberculosis (mtb), there have been no reported attempts to perturb hu function with small molecules. here we report the crystal structure of the n-terminal domain of hu from mtb. we identify a core region within the hu-dna interface that can be targeted using stilbene derivatives. thes ...201424916461
phagocyte nadph oxidase, chronic granulomatous disease and mycobacterial infections.infection of humans with mycobacterium tuberculosis remains frequent and may still lead to death. after primary infection, the immune system is often able to control m. tuberculosis infection over a prolonged latency period, but a decrease in immune function (from hiv to immunosenescence) leads to active disease. available vaccines against tuberculosis are restricted to bcg, a live vaccine with an attenuated strain of m. bovis. immunodeficiency may not only be associated with an increased risk o ...201424916152
the cell envelope glycoconjugates of mycobacterium tuberculosis.tuberculosis (tb) remains the second most common cause of death due to a single infectious agent. the cell envelope of mycobacterium tuberculosis (mtb), the causative agent of the disease in humans, is a source of unique glycoconjugates and the most distinctive feature of the biology of this organism. it is the basis of much of mtb pathogenesis and one of the major causes of its intrinsic resistance to chemotherapeutic agents. at the same time, the unique structures of mtb cell envelope glycocon ...201724915502
expression, purification and preliminary crystallographic analysis of mycobacterium tuberculosis cysq, a phosphatase involved in sulfur metabolism.cysq is part of the sulfur-activation pathway that dephosphorylates 3'-phosphoadenosine 5'-monophosphate (pap) to regenerate adenosine 5'-monophosphate (amp) and free phosphate. pap is the product of sulfate-transfer reactions from sulfotransferases that use the universal sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (paps). in some organisms pap is also the product of paps reductases that reduce sulfate from paps to sulfite. cysq from mycobacterium tuberculosis, which plays an important r ...201424915085
mechanism of dephosphorylation of glucosyl-3-phosphoglycerate by a histidine phosphatase.mycobacterium tuberculosis (mtb) synthesizes polymethylated polysaccharides that form complexes with long chain fatty acids. these complexes, referred to as methylglucose lipopolysaccharides (mglps), regulate fatty acid biosynthesis in vivo, including biosynthesis of mycolic acids that are essential for building the cell wall. glucosyl-3-phosphoglycerate phosphatase (gpgp, ec 5.4.2.1), encoded by rv2419c gene, catalyzes the second step of the pathway for the biosynthesis of mglps. the molecular ...201424914210
a multicenter clinical evaluation of mycobacterium tuberculosis igg/igm antibody detection using the colloidal gold method.a specific immunoassay method with the colloidal gold labeling technique has been developed more and more for tuberculosis (tb) diagnosis. the aim of this multicenter clinical evaluation was to evaluate the performance of a new serological diagnostic kit (the trustline tb igg/igm rapid test kit) for the detection of mycobacterium tuberculosis infection in china, with the aupu tb ab (igg) colloidal gold test kit being used as a control. a total of 1,009 specimens were collected from three tb hosp ...201424913311
drug resistance and molecular epidemiology of mycobacterium tuberculosis in mexico: a systematic review.to compare drug resistance (dr) rates and genetic diversity of mycobacterium tuberculosis strains from different states of mexico.201424912522
first insight into the genotypic diversity of clinical mycobacterium tuberculosis isolates from gansu province, china.investigations of mycobacterium tuberculosis genetic diversity in china have indicated a significant regional distribution. the aim of this study was to characterize the genotypes of clinical m. tuberculosis isolates obtained from gansu, which has a special geographic location in china.201424911588
increased frequency of ilt2-expressing cd56(dim)cd16(+) nk cells correlates with disease severity of pulmonary tuberculosis.the functional role of ilt2 in anti-tuberculosis immunity remains to be elucidated. in this study, we investigated expression and functions of ilt2 on nk cells during tb infection. the frequency of cd56(dim)cd16(+) nk cells that expressed ilt2 was significantly elevated in patients with active pulmonary tb as compared with tuberculin-positive healthy controls (p < 0.0001). tb patients with mycobacterium tuberculosis smear/culture-positive result had significantly higher frequency of ilt2-express ...201424909369
[role of molecular adjuvants tbhsp and mt in the preparation of monoclonal antibody against phosphatase of regenerating liver-3].to explore the adjuvant effects of mycobacterium tuberculosis heat shock protein (tbhsp) and mycobacterium tuberculosis t cell stimulatory epitope (mt) in the preparation of the monoclonal antibody (mab) against phosphatase of regenerating liver-3 (prl-3).201424909283
[preparation of an autophagy-targeted antituberculosis dna vaccine encoding lpqh fused with lc3].to construct an autophagy-targeted vaccine harboring the genes encoding lipoprotein antigen precursor lpqh from mycobacterium tuberculosis and microtubule-associated protein light chain-3(lc3), and to investigate its efficacy of inducing and targeting autophagy.201424909277
elisa-based assay for ip-10 detection from filter paper samples.ip-10 is a small pro-inflammatory chemokine secreted primarily from monocytes and fibroblasts. alterations in ip-10 levels have been associated with inflammatory conditions including viral and bacterial infections, immune dysfunction, and tumor development. ip-10 is increasingly recognized as a biomarker that predicts severity of various diseases and can be used in the immunodiagnostics of mycobacterium tuberculosis and cytomegalovirus infection. here, we describe an elisa-based method to detect ...201424908292
insights into the population structure of mycobacterium tuberculosis using spoligotyping and rdrio in a southeastern brazilian prison unit.tuberculosis (tb) is still a serious public health problem, continuing to be an important threat for confined populations. we used spoligotyping to estimate the genotypic clades of mycobacterium tuberculosis isolates from inmates in two blocks in a southeastern brazilian prison unit, with tb incidence rate of 8185/100.000. the latin american mediterranean (lam) clade is well represented in the country, and the lam specific molecular markers, rd(rio) large sequence polymorphism and the snp on the ...201424907670
mycobacterial 3-hydroxyacyl-l-thioester dehydratase y derived from mycobacterium tuberculosis induces cox-2 expression in mouse macrophages through mapk-nf-κb pathway.tuberculosis (tb) is a leading cause of global mortality due to infectious diseases. expression of cyclooxygenase-2 (cox-2) acts as an important influencing factor favoring bacillary survival during tb infection. in this study, we investigated the mycobacterium tuberculosis proteins recognized by sera from tb patient collected before and after anti-tb therapy by dynamic immunoproteomics and identified a novel immune-regulating protein 3-hydroxyacyl-l-thioester dehydratase y (htdy), which could i ...201424907510
diminished systemic and antigen-specific type 1, type 17, and other proinflammatory cytokines in diabetic and prediabetic individuals with latent mycobacterium tuberculosis infection.diabetes mellitus type 2 (dm) is known to be a major risk factor for the development of active tuberculosis, although its influence on latent mycobacterium tuberculosis infection (hereafter, "latent infection") remains poorly characterized.201424907382
mycobacterium tuberculosis keto-mycolic acid and macrophage nuclear receptor tr4 modulate foamy biogenesis in granulomas: a case of a heterologous and noncanonical ligand-receptor pair.the cell wall of mycobacterium tuberculosis is configured of bioactive lipid classes that are essential for virulence and potentially involved in the formation of foamy macrophages (fms) and granulomas. our recent work established crosstalk between m. tuberculosis cell wall lipids and the host lipid-sensing nuclear receptor tr4. in this study, we have characterized, identified, and adopted a heterologous ligand keto-mycolic acid from among m. tuberculosis lipid repertoire for the host orphan nr ...201424907344
molecular and phenotypic characterization of multidrug-resistant mycobacterium tuberculosis isolates resistant to kanamycin, amikacin, and capreomycin in china.although second-line anti-tuberculosis (tb) injectable drugs have been widely used to improve treatment outcomes of multidrug-resistant tb (mdr-tb), little is known about the prevalence and mechanism of second-line injectable drug resistance among mdr mycobacterium tuberculosis isolates in china. here, we found that 12.7 % (20/158) of isolates showed resistance to at least one second-line injectable drug among 158 mdr isolates. at the same time, there were 16 (10.1 %) strains resistant to kanamy ...201424906439
clonal analysis of the t-cell response to in vivo expressed mycobacterium tuberculosis protein rv2034, using a cd154 expression based t-cell cloning method.tuberculosis (tb), caused by mycobacterium tuberculosis (mtb), remains a leading cause of death worldwide. a better understanding of the role of cd4+ and cd8+ t cells, which are both important to tb protection, is essential to unravel the mechanisms of protection and to identify the key antigens seen by these t cells. we have recently identified a set of in vivo expressed mtb genes (ive-tb) which is expressed during in vivo pulmonary infection in mice, and shown that their encoded antigens are p ...201424905579
interaction of 2-oxoglutarate dehydrogenase odha with its inhibitor odhi in corynebacterium glutamicum: mutants and a model.pyruvate dehydrogenase and oxoglutarate dehydrogenase catalyze key reactions in central metabolism. in corynebacterium glutamicum and related bacteria like mycobacterium tuberculosis both activities reside in a novel protein supercomplex with the fusion protein odha catalyzing the conversion of oxoglutarate to succinyl-coenzyme a. this activity is inhibited by the forkhead-associated (fha) domain of the small autoinhibitory protein odhi. here we used a biological screen which enabled us to isola ...201424905147
molecular patterns of multidrug resistance of mycobacterium tuberculosis in georgia.tuberculosis (tb) infections caused by multidrug-resistant mycobacterium tuberculosis (mdr mtb) remain a significant public health concern worldwide. georgia has a high prevalence of mdr mtb. the genetic mechanisms underlying the emergence of mdr mtb strains in this region are poorly understood and need to be determined for developing better strategies for tb control. this study investigated the frequency of major drug resistance mutations across rpob, katg and inha loci of georgian mdr mtb stra ...201324904758
comparison of the genotype(®) mtbc molecular genetic assay with culture methods in the diagnosis of tuberculosis.clinical samples from 433 patients pre-diagnosed with tuberculosis in konya, turkey, were investigated prospectively to compare the genotype(®) mtbc test (genotype(®) mtbc) with conventional "gold standard" culture methods.201424904667
the pgrs domain from pe_pgrs33 of mycobacterium tuberculosis is target of humoral immune response in mice and humans.the pe_pgrs33 protein is a member of the pe family, which encompasses the pe and the pe_pgrs subfamilies. among pe_pgrs's, this protein is one of the most studied antigens and its immunomodulatory properties are influence by both pe and pgrs domains. however, the contribution of these domains to the host immune recognition of the pe_pgrs33 protein and their potential role in latent tuberculosis infection in humans is still unknown. in this study, the immunogenic properties of the complete pe_pgr ...201424904584
draft genome sequence of the mycobacterium tuberculosis clinical isolate c2, belonging to the latin american-mediterranean family.tuberculosis remains a major infectious disease in taiwan. here we present the draft genome sequence of the mycobacterium tuberculosis c2 strain, belonging to the latin american-mediterranean lineage. the draft genome sequence comprises 4,453,307 bp with a g+c content of 65.6%, revealing 4,390 coding genes and 45 trna genes.201424903871
fluoroquinolone resistance and mycobacterium tuberculosis: cap guidelines play an important role. 201424903803
second worldwide proficiency study on variable number of tandem repeats typing of mycobacterium tuberculosis complex.the quality of variable number of tandem repeats (vntr) typing of mycobacterium tuberculosis was first investigated in 2009 in 37 laboratories worldwide. the results revealed an inter- and intra-laboratory reproducibility of respectively 60% and 72%. these data spurred an improvement in laboratory-specific assays and global standardisation of vntr typing.201424903798
primary drug resistance among pulmonary treatment-naïve tuberculosis patients in amazonas state, brazil.multidrug-resistant tuberculosis (mdr-tb) is the main indicator of previous treatment in tuberculosis (tb) patients. mdr-tb among treatment-naïve patients indicates infection with drug-resistant mycobacterium tuberculosis strains, and such cases are considered primary drug-resistant cases.201424903793
outbreak of pyrazinamide-monoresistant tuberculosis identified using genotype cluster and social media analysis.monoresistance to pyrazinamide (pza) has infrequently been associated with mycobacterium tuberculosis.201424903792
is introducing rapid culture into the diagnostic algorithm of smear-negative tuberculosis cost-effective?in 2007, the world health organization recommended introducing rapid mycobacterium tuberculosis culture into the diagnostic algorithm of smear-negative pulmonary tuberculosis (tb).201424903790
high tuberculosis prevalence in children exposed at home to drug-resistant tuberculosis.urban karachi, pakistan.201424903786
increased level of acute phase reactants in patients infected with modern mycobacterium tuberculosis genotypes in mwanza, tanzania.there is increasing evidence to suggest that different mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (tb). certain m. tuberculosis genotypes/lineages have been shown to be more likely to cause active tb in human populations from a distinct genetic ancestry. this study describes the genetic biodiversity of m. tuberculosis genotypes in mwanza city, tanzania and the clinical presentation of the disease caused by isolates of different lineages.201424903071
false-positive xpert® mtb/rif assays in previously treated patients: need for caution in interpreting results.xpert(®) mtb/rif is the initial diagnostic test of choice for tuberculosis (tb). it is not known if false-positive results are more common in previously treated patients. we report four patients with successful treatment for tb up to 5 years previously who presented with respiratory tract infection and were xpert-positive, but had negative tb cultures and clinical improvement without anti-tuberculosis treatment. we hypothesise that the xpert results were false-positive due to the presence of dea ...201424902569
a molecular transport medium for collection, inactivation, transport, and detection of mycobacterium tuberculosis.in many parts of the world, the diagnosis of tuberculosis (tb) has rapidly shifted to molecular detection and sequencing formats. the collection and transport of mycobacterium tuberculosis specimens thus remains a challenging problem where tb is common and the infrastructure required for ensuring sample integrity is lacking. primestore(®) molecular transport medium (mtm) addresses this problem, rapidly inactivating/killing m. tuberculosis while preserving genomic dna even at elevated temperature ...201424902564
linezolid in the treatment of extensively drug-resistant tuberculosis.to investigate the linezolid (lzd) treatment outcome and correlation between in vitro susceptibility to lzd and clinical outcome.201424902521
strong decrease in streptomycin-resistance and absence of xdr 12 years after the reorganization of the national tuberculosis control program in the central region of cameroon.in the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (mdr) were reported from the central region of cameroon. this work assesses drug resistant tuberculosis in this region 12 years after reorganization of the national tuberculosis control program (ntcp).201424901982
crystallographic and spectroscopic insights into heme degradation by mycobacterium tuberculosis mhud.mycobacterium heme utilization degrader (mhud) is a heme-degrading protein from mycobacterium tuberculosis responsible for extracting the essential nutrient iron from host-derived heme. mhud has been previously shown to produce unique organic products compared to those of canonical heme oxygenases (hos) as well as those of the isdg/i heme-degrading enzymes from staphylococcus aureus. here, we report the x-ray crystal structure of cyanide-inhibited mhud (mhud-heme-cn) as well as detailed (1)h nuc ...201424901029
design and syntheses of anti-tuberculosis agents inspired by btz043 using a scaffold simplification strategy.tuberculosis (tb), a disease caused by mycobacterium tuberculosis (mtb), is a global public health concern because of the emergence of various resistant strains. benzothiazin-4-ones (btzs), represented by btz043, are a promising new class of agents for the treatment of tuberculosis and have been shown to kill mtb in vitro, ex vivo, and in mouse models of tb. herein we report the design and syntheses of nitroaromatic sulfonamide, reverse-amide, and ester classes of anti-tb agents using a scaffold ...201424900885
biarylmethoxy nicotinamides as novel and specific inhibitors of mycobacterium tuberculosis.a whole cell based screening effort on a focused library from corporate collection resulted in the identification of biarylmethoxy nicotinamides as novel inhibitors of m. tuberculosis (mtu) h37rv. the series exhibited tangible structure-activity relationships, and during hit to lead exploration, a cellular potency of 100 nm was achieved, which is an improvement of >200-fold from the starting point. the series is very specific to mtu and noncytotoxic up to 250 μm as measured in the mammalian cell ...201424900867
discovery of tetrahydropyrazolopyrimidine carboxamide derivatives as potent and orally active antitubercular agents.tetrahydropyrazolo[1,5-a]pyrimidine scaffold was identified as a hit series from a mycobacterium tuberculosis (mtb) whole cell high through-put screening (hts) campaign. a series of derivatives of this class were synthesized to evaluate their structure-activity relationship (sar) and structure-property relationship (spr). compound 9 had a promising in vivo dmpk profile in mouse and exhibited potent in vivo activity in a mouse efficacy model, achieving a reduction of 3.5 log cfu of mtb after oral ...201324900693
identification of 1-[4-benzyloxyphenyl)-but-3-enyl]-1h-azoles as new class of antitubercular and antimicrobial agents.a series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1h-azoles has been identified as potent antitubercular agents against mycobacterium tuberculosis. synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with mic value as low as 1.56, 1.56, and 0.61 μg/ml, respectively, comparab ...201324900592
the visual diagnosis of tuberculous pleuritis under medical thoracoscopy: a retrospective series of 91 cases.despite progress of medical, the fast and accurate diagnosis of tuberculous pleuritis (tp) continues to be a challenge, mainly because of the lack of specific clinical features and the difficulty in isolating the mycobacterium tuberculosis.201424899607
cutting edge: vitamin d regulates lipid metabolism in mycobacterium tuberculosis infection.vitamin d has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat because of multidrug resistance. previous work established that vitamin d induces macrophage antimicrobial functions against mycobacterium tuberculosis. in this article, we report a novel, metabolic role for vitamin d in tuberculosis identified through integrated transcriptome and mechanistic studies. transcriptome analysis revealed an association between vitamin d r ...201424899504
diagnostic accuracy of a molecular drug susceptibility testing method for the antituberculosis drug ethambutol: a systematic review and meta-analysis.ethambutol (emb) is a first-line antituberculosis drug; however, drug resistance to emb has been increasing. molecular drug susceptibility testing (dst), based on the embb gene, has recently been used for rapid identification of emb resistance. the aim of this meta-analysis was to establish the accuracy of molecular assay for detecting drug resistance to emb. pubmed, embase, and web of science were searched according to a written protocol and explicit study selection criteria. measures of diagno ...201424899018
clinical access to bedaquiline programme for the treatment of drug-resistant tuberculosis.while clinical disease caused by drug-sensitive mycobacterium tuberculosis (mtb) can usually be treated successfully, clinical disease caused by drug-insensitive mtb is associated with a poorer prognosis. in december 2012, a new drug, bedaquiline, was approved by the us food and drug administration. this article documents the process whereby the national department of health, right to care and médecins sans frontières obtained access to this medication for south africans who might benefit from s ...201424897814
vulnerability of homeless people in tehran, iran, to hiv, tuberculosis and viral hepatitis.homeless people are at risk of contracting communicable infectious diseases, as they indulge in risky behaviours and lifestyle. this study was conducted to determine the prevalence of the aforementioned infections and related risk behaviours among homeless people in tehran.201424896247
insights into the bonding pattern for characterizing the open and closed state of the substrate-binding loop in mycobacterium tuberculosis inha.direct inha inhibitors, which interact with the substrate-binding loop (sbl) and order it into a closed state, are thought to be potential anti-multidrug-resistant tuberculosis molecules. thus, developing parameters to distinguish between the open and closed state of sbl can help in screening the potent inhibitors with loop ordering properties.201424895891
specialized transduction designed for precise high-throughput unmarked deletions in mycobacterium tuberculosis.specialized transduction has proven to be useful for generating deletion mutants in most mycobacteria, including virulent mycobacterium tuberculosis. we have improved this system by developing (i) a single-step strategy for the construction of allelic exchange substrates (aes), (ii) a temperature-sensitive shuttle phasmid with a greater cloning capacity than phae87, and (iii) bacteriophage-mediated transient expression of site-specific recombinase to precisely excise antibiotic markers. the meth ...201424895308
mycobacterium tuberculosis lsr2 is a global transcriptional regulator required for adaptation to changing oxygen levels and virulence.to survive a dynamic host environment, mycobacterium tuberculosis must endure a series of challenges, from reactive oxygen and nitrogen stress to drastic shifts in oxygen availability. the mycobacterial lsr2 protein has been implicated in reactive oxygen defense via direct protection of dna. to examine the role of lsr2 in pathogenesis and physiology of m. tuberculosis, we generated a strain deleted for lsr2. analysis of the m. tuberculosis δlsr2 strain demonstrated that lsr2 is not required for ...201424895305
synthesis of new verapamil analogues and their evaluation in combination with rifampicin against mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein rv1258c.new verapamil analogues were synthesized and their inhibitory activities against mycobacterium tuberculosis h37rv determined in vitro alone and in combination with rifampicin (rif). some analogues showed comparable activity to verapamil and exhibited better synergies with rif. molecular docking studies of the binding sites of rv1258c, a m. tuberculosis efflux protein previously implicated in intrinsic resistance to rif, suggested a potential rationale for the superior synergistic interactions ob ...201424894561
large bilateral tubercular pyosalpinx in a young woman with genitourinary malformation: a case report.tuberculosis is a chronic infectious disease, and the morbidity associated with it has major health implications. when tuberculosis affects the genital organs of young females, it has the devastating effect of causing irreversible damage to their fallopian tubes, resulting in a possible tubercular pyosalpinx and infertility. however, the disease often remains silent or presents with very few specific symptoms. in adolescents and young women, tuberculosis can also present with hypogastric recurre ...201424894269
evaluation of mycobacterium tuberculosis cross-resistance to isoniazid, rifampicin and levofloxacin with their respective structural analogs.the emergence of drug-resistant, multidrug-resistant and extensively drug-resistant tuberculosis (tb) is of major public health concern in several countries. in this study, the pharmacodynamic relationships among the structural analogs of antibiotics belonging to the same family were taken into consideration. the aim of this study was to compare the susceptibility of mycobacterium tuberculosis to isoniazid (inh), rifampicin and levofloxacin (lx) to their respective structural analogs, which are ...201424894185
novel vaccination strategies against tuberculosis.the tuberculosis (tb) pandemic continues to rampage despite widespread use of the bcg (bacillus calmette-guérin) vaccine. novel vaccination strategies are urgently needed to arrest global transmission and prevent the uncontrolled development of multidrug-resistant forms of mycobacterium tuberculosis. over the last two decades, considerable progress has been made in the field of vaccine development with numerous innovative preclinical candidates and more than a dozen vaccines in clinical trials. ...201424890836
rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm.there is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (mdr-tb). no diagnostic algorithm has been validated in this population. we hypothesized that pnca sequencing added to rpob mutation analysis can accurately identify patients with pyrazinamide-resistant mdr-tb. we identified from the dutch national database (2007-11) patients with a positive mycobacterium tuberculosis culture containing a mutation in the rpob gene. in these cases, ...201424890253
whole-genome sequencing to detect recent transmission of mycobacterium tuberculosis in settings with a high burden of tuberculosis.whole genome sequencing (wgs) of mycobacterium tuberculosis has been used to trace the transmission of m. tuberculosis, the causative agent of tuberculosis (tb). previously published studies using wgs were conducted in developed countries with a low tb burden. we sought to evaluate the relative usefulness of traditional vntr and snp typing methods, wgs and epidemiological investigations to study the recent transmission of m. tuberculosis in a high tb burden country. we conducted epidemiological ...201424888866
clinical mycobacterium tuberculosis isolates from the population of łódź, poland stimulated macrophages to the lower production of il-12 and no when compared to the virulent h37rv strain.the course of mycobacterium tuberculosis (mtb) infection and the outcome of clinically active tuberculosis depend on the complex interactions between the host immune system and m. tuberculosis properties. the objective of the study was to examine the virulence of local mtb isolates from the population of łódź in poland. thirty six local mtb strains of total 234 with known transmission in the local community were randomly selected for the study. the production of il-12 and no by murine macrophage ...201424888865
outbreaks of mycobacterium tuberculosis mdr strains differentially induce neutrophil respiratory burst involving lipid rafts, p38 mapk and syk.neutrophils (pmn) are the first cells to infiltrate the lung after infection, and they play a significant protective role in the elimination of pathogen, by releasing preformed oxidants and proteolytic enzymes from granules and generating ros, thus limiting inflammation by succumbing to apoptosis. in a previous study, we found marked differences in ros-induced apoptosis between two mycobacterium tuberculosis (mtb) strains, m and ra, representative of widespread mtb families in south america, i.e ...201424886274
a rare case of cytomegalovirus, scedosporium apiospermum and mycobacterium tuberculosis in a renal transplant recipient.renal transplant recipients are at high risk of developing multiple infections, often concomitantly because of their immunocompromised status. post renal transplant infections are often elusive and require extensive evaluation for proper diagnosis and treatment. a high index of suspicion is required and an attempt should be made to confirm the microbiological diagnosis from each site involved to rule out multiple infections.201424885965
a web-based protein interaction network visualizer.interaction between proteins is one of the most important mechanisms in the execution of cellular functions. the study of these interactions has provided insight into the functioning of an organism's processes. as of october 2013, homo sapiens had over 170000 protein-protein interactions (ppi) registered in the interologous interaction database, which is only one of the many public resources where protein interactions can be accessed. these numbers exemplify the volume of data that research on t ...201424885165
acid suppressive agents and risk of mycobacterium tuberculosis: case-control study.the acid-suppressive agents have been linked with an increased risk of infectious disease. the relationship between these drugs and mycobacterium tuberculosis (tb) was not been reported.201424884853
automated ensemble assembly and validation of microbial genomes.the continued democratization of dna sequencing has sparked a new wave of development of genome assembly and assembly validation methods. as individual research labs, rather than centralized centers, begin to sequence the majority of new genomes, it is important to establish best practices for genome assembly. however, recent evaluations such as gage and the assemblathon have concluded that there is no single best approach to genome assembly. instead, it is preferable to generate multiple assemb ...201424884846
sequence analysis for detection of drug resistance in mycobacterium tuberculosis complex isolates from the central region of cameroon.the potential of genetic testing to rapidly diagnose drug resistance has lead to the development of new diagnostic assays. however, prior to implementation in a given setting, the association of specific mutations with specific drug resistance phenotypes should be evaluated. the purpose of this study was to evaluate molecular markers in predicting drug resistance in the central region of cameroon.201424884632
evaluation of the relationship between smear positivity and high-resolution ct findings in children with pulmonary tuberculosis.the aim of this study is to find a relationship between the radiological manifestations of childhood tuberculosis on a high-resolution computed tomography (hrct) and the results of sputum smear. this study aims to propose an alternative indicator of infectivity in terms of prevention of disease transmission through selective isolation policy in children whose clinical condition is highly suggestive of tuberculosis.201424883144
emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care.infectious diseases are the leading cause of death worldwide. among them, tuberculosis (tb) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (mdr) and extensively drug-resistant (xdr) mycobacterium tuberculosis (mtb). mdr-mtb strains are resistant to first-line anti-tb drugs such as isoniazid and rifampicin; whereas xdr-mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-tb injecta ...201424882226
predicting natural product value, an exploration of anti-tb drug space.covering: january 1990 to december 2012. mycobacterium tuberculosis (mtb) still remains a deadly pathogen two decades after the announcement of tuberculosis (tb) as a global health emergency by the world health organization. in last few years new drug combinations have shown promising potential to significantly shorten tb treatment times. however there are very few new chemical entities being developed to treat this global threat. from january 1990 to december 2012, 949 anti-mycobacterium natura ...201424881816
persistently retained interferon-gamma responsiveness in individuals with a history of pulmonary tuberculosis.the interferon gamma (ifn-γ) release assays (igras) are the best method of detecting mycobacterium tuberculosis infection. however, reports on igras results obtained during and right after the treatment of tuberculosis (tb) have presented differing results. some studies have shown declining responses, whereas other reports described persistent, fluctuating, or increasing responses. we postulated that the igra-positivity will decrease or revert long time after treatment of tb, and thus, evaluated ...201424881649
microbiology devices; reclassification of nucleic acid-based systems for mycobacterium tuberculosis complex in respiratory specimens. final rule.the food and drug administration (fda) is reclassifying nucleic acid-based in vitro diagnostic devices for the detection of mycobacterium tuberculosis complex in respiratory specimens from class iii (premarket approval) into class ii (special controls). fda is also issuing the special controls guideline entitled ''class ii special controls guideline: nucleic acid-based in vitro diagnostic devices for the detection of mycobacterium tuberculosis complex in respiratory specimens.'' these devices ar ...201424881095
protective efficacy of piperine against mycobacterium tuberculosis.piperine a trans-trans isomer of 1-piperoyl-piperidine was evaluated for its immunomodulatory activity to enhance the efficacy of rifampicin in a murine model of mycobacterium tuberculosis infection. in-vitro immunomodulation of piperine was tested on mouse splenocytes for lymphocyte proliferation, cytokine production and macrophage activation. protective efficacy of piperine was tested in a mice infection model of m. tuberculosis for the activation of th-1 response and synergistic combination e ...201424880706
a multicenter study of cross-priming amplification for tuberculosis diagnosis at peripheral level in china.cross-priming amplification (cpa) has been shown to rapidly and effectively detect mycobacterium tuberculosis (mtb) in sputum samples under isothermal conditions. however, no performance data exist from peripheral-level tuberculosis (tb) clinics in tuberculosis-endemic countries. we conducted a clinical trial at four county-level tb clinics in china to evaluate the effectiveness of the cpa assay. tb suspects were continuously enrolled by a clinician at each clinic. following informed consent, ea ...201424880705
mycobacterium tuberculosis infection in young children: analyzing the performance of the diagnostic tests.this study evaluated the performance of the tuberculin skin test (tst) and quantiferon-tb gold in-tube (qft) and the possible association of factors which may modify their results in young children (0-6 years) with recent contact with an index tuberculosis case.201424879374
theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.a series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. the newly synthesized compounds were evaluated for their in vitro activity against mycobacterium tuberculosis h37rv. the activity varied depending on the amino acid fragments and in seven cases exerted excellent values with mics 0.46-0.26 ...201424878196
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