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expression levels of 10 candidate genes in lung tissue of vaccinated and tb-infected cynomolgus macaques.the expression of ten tuberculosis candidate genes in lung and lymph nodes of cynomolgus macaques vaccinated and experimentally infected with mycobacterium tuberculosis (mtb) was quantified. the expression of tnfα, il10, il1β, tlr4, il17, il6, il12, and inos in the lungs of vaccinated animals was higher than that of non-vaccinated animals.201323802315
paediatric chronic suppurative otitis media in the free state province: clinical and audiological features.chronic suppurative otitis media (csom) is a chronic infection of the middle ear cleft. in sub-saharan africa >50% of cases occur in children <10 years of age.201323802210
potential function of granulysin, other related effector molecules and lymphocyte subsets in patients with tb and hiv/tb coinfection.host effector mechanism against mycobacterium tuberculosis (mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. coordinated release of cytolytic effector molecules from nk cells and effector t cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (tb) is still controversy.201323801887
discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in mycobacterium tuberculosis.functional assignment of enzymes encoded by the mycobacterium tuberculosis genome is largely incomplete despite recent advances in genomics and bioinformatics. here, we applied an activity-based metabolomic profiling method to assign function to a unique phosphatase, rv1692. in contrast to its annotation as a nucleotide phosphatase, metabolomic profiling and kinetic characterization indicate that rv1692 is a d,l-glycerol 3-phosphate phosphatase. crystal structures of rv1692 reveal a unique archi ...201323801751
a genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of mycobacterium tuberculosis beijing genotype.the beijing genotype of mycobacterium tuberculosis (mtb) is one of the most successful mtb lineages that has disseminated in the world. in china, the rate of multidrug-resistant (mdr) tuberculosis is significantly higher than the global average rate, and the beijing genotype strains take the largest share of mdr strains. to study the genetic basis of the epidemiological findings that beijing genotype has often been associated with tuberculosis outbreaks and drug resistance, we determined the gen ...201323801408
detection of inhibitors of phenotypically drug-tolerant mycobacterium tuberculosis using an in vitro bactericidal screen.many whole cell screens of chemical libraries currently in use are based on inhibition of bacterial growth. the goal of this study was to develop a chemical library screening model that enabled detection of compounds that are active against drug-tolerant non-growing cultures of mycobacterium tuberculosis. an in vitro model of low metabolically active mycobacteria was established with 8 and 30 day old cultures of m. smegmatis and m. tuberculosis, respectively. reduction of resazurin was used as a ...201323800952
identification of a major locus, tnf1, that controls bcg-triggered tumor necrosis factor production by leukocytes in an area hyperendemic for tuberculosis.tumor necrosis factor (tnf) is a key immune regulator of tuberculosis resistance, as exemplified by the highly increased risk of tuberculosis disease among individuals receiving tnf-blocker therapy.201323800941
biological variability and the emergence of multidrug-resistant tuberculosis.a new study demonstrates that bacterial mutation rates associated with the mycobacterium tuberculosis lineage most commonly linked to multidrug-resistant tuberculosis are multifold higher than shown in previous studies. this discovery, when considered together with recent findings on pharmacokinetic variability in patients, leads to new models of how multidrug-resistant tuberculosis arises, with direct therapeutic implications.201323800865
mapping is6110 in high-copy number mycobacterium tuberculosis strains shows specific insertion points in the beijing genotype.mycobacterium tuberculosis beijing strains are characterized by a large number of is6110 copies, suggesting the potential implication of this element in the virulence and capacity for rapid dissemination characteristic of this family. this work studies the insetion points of is6110 in high-copy clinical isolates specifically focusing on the beijing genotype.201323800083
diarylcoumarins inhibit mycolic acid biosynthesis and kill mycobacterium tuberculosis by targeting fadd32.infection with the bacterial pathogen mycobacterium tuberculosis imposes an enormous burden on global public health. new antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. here, we describe the identification of a 4,6-diaryl-5,7-dimethyl coumarin series that kills m. tuberculosis by inhibiting fatty acid degradation protein d32 (fadd32), an enzyme that is required for biosynt ...201323798446
treatment outcomes in aids-related diffuse large b-cell lymphoma in the setting roll out of combination antiretroviral therapy in south africa.long-term survival for patients with aids-related diffuse large b-cell lymphoma (dlbcl) is feasible in settings with available combination antiretroviral therapy (cart). however, given limited oncology resources, outcomes for aids-associated dlbcl in south africa are unknown.201323797692
radiologic responses in cynomolgus macaques for assessing tuberculosis chemotherapy regimens.trials to test new drugs currently in development against tuberculosis in humans are impractical. all animal models to prioritize new regimens are imperfect, but nonhuman primates (nhps) infected with mycobacterium tuberculosis develop active tuberculosis (tb) disease with a full spectrum of lesion types seen in humans. serial 2-deoxy-2-[(18)f]-fluoro-d-glucose (fdg) positron emission tomography (pet) with computed tomography (ct) imaging was performed on cynomolgus macaques during infection and ...201323796926
commercial mpt64-based tests for rapid identification of mycobacterium tuberculosis complex: a meta-analysis.we did a systematic review and meta-analysis of published studies to evaluate the accuracy of commercial mpt64-based immunochromatographic tests for rapid identification of mycobacterium tuberculosis complex.201323796870
quantiferon to diagnose infection by mycobacterium tuberculosis: performance in infants and older children.quantiferon value to diagnose tuberculosis (tb) in young children remains to be clarified. to this aim qf-tb-it performance was evaluated in a large series of immunocompetent children that were stratified according to age and clinical conditions.201323796868
multi-drug resistance tuberculosis (mdr-tb) in kassala state, eastern sudan.this study investigates the prevalence of drug resistance and mutations in rpob gene among mycobacterium tuberculosis isolates from kassala state, sudan. in a cross-sectional study during 2011, sputum specimens (n = 90) were examined microscopically and grown cultures were identified by analysing is6110 insertion sequence. antimicrobial sensitivity and mutations in the rpob gene were determined. of the 90 specimens found which were positive for acid-fast bacilli (afb), 65 (72.2%) showed growth o ...201323796674
assessment of diagnostic techniques of urinary tuberculosis.early diagnosis of active tuberculosis remains an elusive challenge. in addition, one third of the world's population is latently infected with mycobacterium tuberculosis (mtb) and up to 10% of infected individuals develop tuberculosis (tb) in their lifetime. in this investigation, the incidence of urinary tuberculosis among renal patients was studied. three hundreds urine samples were processed for detection of mtb by ziehl-neelsen (zn) smear examination, lowenstein jensen (lj) medium, radiomet ...201323795272
diagnosis of tuberculous peritonitis using endoscopic ultrasound-guided fine-needle aspiration biopsy of the peritoneum.tuberculous peritonitis is prevalent in developing countries and its diagnosis is still challenging due to the lack of specific clinical characteristics and the difficulty in obtaining tissue from the peritoneum without laparoscopy. endoscopic ultrasound - guided fine needle aspiration is emerging as the most effective and safe method for obtaining tissue from the structures surrounding the gut lumen. our study aimed to elucidate the efficacy of endoscopic ultrasound-fine needle aspiration of th ...201323794347
the current state of tuberculosis vaccines.tuberculosis continues to persist despite widespread use of bcg, the only licensed vaccine to prevent tb. bcg's limited efficacy coupled with the emergence of drug-resistant strains of mycobacterium tuberculosis emphasizes the need for a more effective vaccine for combatting this disease. however, the development of a tb vaccine is hindered by the lack of immune correlates, suboptimal animal models, and limited funding. an adolescent/adult vaccine would have the greatest public health impact, bu ...201323792698
predicting mycobacterium tuberculosis in patients with community-acquired pneumonia.the 22 risk factors suggested by the centers for disease control and prevention (cdc) to predict patients at risk for mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (cap). we evaluated which of the cdc risk factors best predict m. tuberculosis in these patients. to our knowledge, this is the first time a score has been developed assessing these risk factors. this was a secondary analysis of 6976 patients hospitalised with cap enrolle ...201423794467
high resolution melting curve assay for rapid detection of drug-resistant mycobacterium tuberculosis.we developed and evaluated a high resolution melting (hrm) curve assay by using real-time pcr for the detection of the most frequent mutations of mycobacterium tuberculosis, which are responsible for the resistance of four anti-tb drugs: rifampicin, isoniazid, ethambutol, and streptomycin. the hrm assay was successfully used for the detection of dominant mutations: a516v, h526a, h526t, s531l, l533p, and a516g/s531l in rpob; s315t, and s315a in katg; -15c/t, and -8t/c in mab-inha; m306i in embb; ...201323793795
a single-cell perspective on non-growing but metabolically active (ngma) bacteria.a long-standing and fundamental problem in microbiology is the non-trivial discrimination between live and dead cells. the existence of physically intact and possibly viable bacterial cells that fail to replicate during a more or less protracted period of observation, despite environmental conditions that are ostensibly propitious for growth, has been extensively documented in many different organisms. in clinical settings, non-culturable cells may contribute to non-apparent infections capable o ...201323793585
inhibition of mycobacterium tuberculosis pkng by non-catalytic rubredoxin domain specific modification: reaction of an electrophilic nitro-fatty acid with the fe-s center.pkng from mycobacterium tuberculosis is a ser/thr protein kinase that regulates key metabolic processes within the bacterial cell as well as signaling pathways from the infected host cell. this multidomain protein has a conserved canonical kinase domain with n- and c-terminal flanking regions of unclear functional roles. the n-terminus harbors a rubredoxin-like domain (rbx), a bacterial protein module characterized by an iron ion coordinated by four cysteine residues. disruption of the rbx-metal ...201323792274
use of strep-tag ii for rapid detection and purification of mycobacterium tuberculosis recombinant antigens secreted by streptomyces lividans.recent results with respect to the secretory production of bio-active mycobacterium tuberculosis proteins in streptomyces have stimulated the further exploitation of this host as a bacterial cell factory. however, the rapid isolation of a recombinant protein by conventional procedures can be a restrictive step. a previous attempt to isolate recombinant antigens fused to the widely used 6his-tag was found to be relatively incompatible with secretory production in the streptomyces host. as an alte ...201323791917
autophagy as an immune effector against tuberculosis.the now well-accepted innate immunity paradigm that autophagy acts as a cell-autonomous defense against intracellular bacteria has its key origins in studies with mycobacterium tuberculosis, an important human pathogen and a model microorganism infecting macrophages. a number of different factors have been identified that play into the anti-mycobacterial functions of autophagy, and recent in vivo studies in the mouse model of tuberculosis have uncovered additional anti-inflammatory and tissue-sp ...201323790398
exploring the contribution of mycobacteria characteristics in their interaction with human macrophages.tuberculosis (tb) is a major health problem. the emergence of multidrug resistant (mdr) mycobacterium tuberculosis (mtb) isolates confounds treatment strategies. in portugal, cases of mdr-tb are reported annually with an increased incidence noted in lisbon. the majority of these mdr-tb cases are due to closely related mycobacteria known collectively as the lisboa family and q1 cluster. genetic determinants linked to drug resistance have been exhaustively studied resulting in the identification o ...201323790221
synthesis and 3d-qsar analysis of 2-chloroquinoline derivatives as h37 rv mtb inhibitors.frequency of tuberculosis is progressively increasing worldwide. new emerging strains of bacilli that are emerging are resistant to the currently available drugs which make this issue more alarming. in this regard, a series of substituted quinolinyl chalcones, quinolinyl pyrimidines, and pyridines were synthesized and evaluated for their antitubercular activity in vitro against mycobacterium tuberculosis h37 rv. to establish the role of the 2-chloroquinoline nucleus as a pharmacophoric group and ...201323790070
mycobacterium tuberculosis cell wall-associated rv3812 protein induces strong dendritic cell-mediated interferon γ responses and exhibits vaccine potential. 201323788727
disruption of mycobactin biosynthesis leads to attenuation of mycobacterium tuberculosis for growth and virulence.low iron availability in the host upregulates the mbt gene cluster of mycobacterium tuberculosis, which is responsible for mycobactin biosynthesis. however, the biological significance of mycobactins in the growth of this pathogen and in disease progression has not been elucidated.201323788726
draft genome sequence of a clinical isolate of mycobacterium tuberculosis strain pr05.we report the annotated genome sequence of a clinical isolate, mycobacterium tuberculosis strain pr05, which was isolated from the human cerebrospinal fluid of a patient diagnosed with tuberculosis.201323788553
whole-genome sequences of four clinical isolates of mycobacterium tuberculosis from tamil nadu, south india.we report the annotated genome sequences of four clinical isolates of mycobacterium tuberculosis from tamil nadu, india.201323788533
determination of critical concentrations of moxifloxacin and gatifloxacin for drug susceptibility testing of mycobacterium tuberculosis in the bactec mgit 960 system.to determine critical concentrations of moxifloxacin and gatifloxacin for rapid evaluation of drug susceptibility of mycobacterium tuberculosis in middlebrook 7h9 broth using the automated system bactec™ mgit™ 960.201323788475
overcoming the limitations of fragment merging: rescuing a strained merged fragment series targeting mycobacterium tuberculosis cyp121. 201323788280
comparison of xpert mtb/rif with probetec et dtb and cobas taqman mtb for direct detection of m. tuberculosis complex in respiratory specimens.nucleic acid amplification assays allow for the rapid and accurate detection of mycobacterium tuberculosis (mtb) directly in clinical specimens thereby facilitating diagnosis of tuberculosis (tb). with the fully automated xpert mtb/rif system (cepheid) an innovative solution of tb diagnostics has been launched. we performed a direct head-to-head comparison of xpert mtb/rif with two widely used commercial assays, probetec et dtb (dtb) (becton-dickinson) and cobas taqman mtb (ctm-mtb) (roche).201323786563
geographical differences associated with single-nucleotide polymorphisms (snps) in nine gene targets among resistant clinical isolates of mycobacterium tuberculosis.alternative diagnostic methods, such as sequence-based techniques, are necessary for increasing the proportion of tuberculosis cases tested for drug resistance. despite the abundance of data on drug resistance, isolates can display phenotypic resistance but lack any distinguishable markers. furthermore, because resistance-conferring mutations develop under antibiotic pressure, different drug regimens could favor unique single-nucleotide polymorphisms (snps) in different geographical regions. a t ...201423784122
resistance of mycobacterium tuberculosis to antibiotics in lao pdr: first multicentric study conducted in 3 hospitals.it is estimated that lao people's democratic republic (lao pdr) ranks fifth among the seven countries most affected by tb in the who western pacific region. however, because of late implementation of mycobacterial culture, no study on resistance to anti-tb drugs had been performed yet. the objective of this study was to document drug resistance rate among patients hospitalized for pulmonary tb in threeprovinces of lao pdr.201323782980
randomized, placebo-controlled phase ii trial of heat-killed mycobacterium vaccae (longcom batch) formulated as an oral pill (v7).one-month phase ii trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic tb vaccine (v7) containing 10 μg of heat-killed mycobacterium vaccae provided by longcom company. immunotherapy and control groups comprised 8 newly diagnosed (1stdx tb; 18.6%), 6 re-treated (rtb; 14%), and 29 multidrug-resistant (mdr-tb; 67.4%) cases distri ...201323782489
n,c-capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of s3 and s1 binding pockets.we identified n,c-capped dipeptides that are selective for the mycobacterium tuberculosis proteasome over human constitutive and immunoproteasomes. differences in the s3 and s1 binding pockets appeared to account for the species selectivity. the inhibitors can penetrate mycobacteria and kill nonreplicating m. tuberculosis under nitrosative stress.201323782398
open window thoracostomy for the treatment of bronchopleural cutaneous fistula -- case report.pleural empyema and bronchopleural fistula (the communication between the pleural space and the airways) are early or late complications of various diseases. we present the case of a 29-year-old patient operated for cavitary pulmonary tuberculosis and giant caseoma at the age of seven, who also had fibrocavitary pulmonary tuberculosis positive for mycobacterium tuberculosis at the age of 19. the patient presented with low grade fever, chills, sweating, cough with mucopurulentsputum, dyspnea on m ...201323781569
synthesis and biological evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives.3-(4-chlorophenyl)-4-substituted pyrazole derivatives were synthesised and tested for their in vitro antifungal activity. some compounds showed very good antifungal activity against four pathogenic strains of fungi. the same compounds exhibited an interesting activity against the tested strain of mycobacterium tuberculosis h37rv. the results suggest that 1,3,4-oxadiazoles and 5-pyrazolinones bearing a core pyrazole scaffold may be promising antifungal and antitubercular agents.201323779132
para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in mycobacterium tuberculosis.para-aminosalicylic acid (pas) is one of the antimycobacterial drugs currently used for multidrug-resistant tuberculosis. although it has been in clinical use for over 60 years, its mechanism(s) of action remains elusive. here we report that pas is a prodrug targeting dihydrofolate reductase (dhfr) through an unusual and novel mechanism of action. we provide evidences that pas is incorporated into the folate pathway by dihydropteroate synthase (dhps) and dihydrofolate synthase (dhfs) to generate ...201323779105
the il-17 g-152a single nucleotide polymorphism is associated with pulmonary tuberculosis in northern spain.interleukin 17 (il-17) is induced during the early stages of tuberculosis infection, playing an important role in the defense against mycobacterial infection. to date, only one study performed in chinese han population has found an association between il-17f sequence variants and susceptibility to tuberculosis, but no relationship has been found with another single nucleotide polymorphism (snp) in il-17a gene (rs2275913).201323778030
vaccination with recombinant mycobacterium tuberculosis pknd attenuates bacterial dissemination to the brain in guinea pigs.we have previously identified mycobacterium tuberculosis pknd to be an important virulence factor required for the pathogenesis of central nervous system (cns) tuberculosis (tb). specifically, pknd mediates bacillary invasion of the blood-brain barrier, which can be neutralized by specific antisera, suggesting its potential role as a therapeutic target against tb meningitis.201323776655
identification of a small molecule with activity against drug-resistant and persistent tuberculosis.a cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule tca1, which has bactericidal activity against both drug-susceptible and -resistant mycobacterium tuberculosis (mtb) and sterilizes mtb in vitro combined with rifampicin or isoniazid. in addition, tca1 has bactericidal activity against nonreplicating mtb in vitro and is efficacious in acute and chronic mtb infection mouse models both alone and combined with rifampicin or isoniazid. tra ...201323776209
tb-iris after initiation of antiretroviral therapy is associated with expansion of preexistent th1 responses against mycobacterium tuberculosis antigens.the role of t-cell responses against mycobacterium tuberculosis antigens in tuberculosis-associated immune reconstitution inflammatory syndrome (tb-iris) is unclear.201323774879
adaptation of mycobacteria on solid, egg-based media to anaerobic conditions and characterization of their diagnostic phenotypes.recent evidence indicates that human pulmonary tuberculous granulomas are hypoxic, and a related dormancy model has been established for mycobacterium tuberculosis using liquid media in tightly sealed tubes. in the present study, we examined the growth capacity of various mycobacterial species on solid, egg-based media under oxygen-limited conditions. during primary anaerobic cultivation on an ogawa egg-based medium, all of the inoculated mycobacterial strains persisted for 10 weeks without dete ...201323774654
protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis.besides joint destruction, extra-articular complications (outside the locomotor system) are frequent in rheumatoid arthritis (ra) patients, especially cardiovascular, hematological and metabolic disorders. here, we evaluated and compared the protective activity of two different doses of mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (gtaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (aia).201323773648
genetic heterogeneity revealed by sequence analysis of mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients.tuberculosis remains a major public health problem. clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. the emergence of drug resistant tubercle bacilli and its association with hiv is a formidable challenge to curb the spread of tuberculosis. there have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifes ...201323773324
pleural effusion during acute myeloid leukemia induction chemotherapy: a perplexing case.we are reporting a case of pneumonia associated with pleural effusion during the neutropenic phase of induction chemotherapy. in spite of being adenosine deaminase negative, the pleural effusion responded only to empiric therapy with antitubercular agents. the diagnosis was confirmed with positive pcr testing for mycobacterium tuberculosis.201323771378
mycobacterium tuberculosis isolates from rio de janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pnca gene.it has been widely accepted, that pyrazinamide (pza) resistance in mycobacterium tuberculosis is correlated with mutations in the pnca gene. but since years researchers have been puzzled by the fact that up to 30% of pza resistant strains do not show any correlation between pza resistance and mutations in the pnca gene, and thus may vary with geographic area. the objective of the study was to investigate the correlation between pza susceptibility and mutations in pnca gene in m. tuberculosis iso ...201323770140
a prospective longitudinal study evaluating a t-cell-based assay for latent tuberculosis infection in health-care workers in a general hospital in beijing.the health-care workers (hcws) are at high risk of acquiring infection with mycobacterium tuberculosis. the objectives of this study were to compare the performance of the t-spot.tb and tuberculin skin test (tst) for latent tuberculosis infection (ltbi), evaluate diagnostic concordance and risk factors for ltbi, and observe the progression to active tuberculosis (tb) disease among hcws in a general hospital in beijing.201323769554
clarification on the decarboxylation mechanism in kasa based on the protonation state of key residues in the acyl-enzyme state.the β-ketoacyl acp synthase i (kasa) is a promising drug target because it is essential for the survival of mycobacterium tuberculosis , a causative agent of tuberculosis. it catalyzes a condensation reaction that comprises three steps. the resulting elongated acyl chains are subsequently needed for the cell wall construction. while the mechanism of the first step (acylation of cys171 in the active site) is straightforward already, the second step (decarboxylation of malonyl substrate) has been ...201323768199
peliosis hepatis due to disseminated tuberculosis in a patient with aids.peliosis hepatis is a rare histopathological entity of unknown etiology. we present a case of peliosis hepatis in a 44-year-old man with disseminated tuberculosis and acquired immunodeficiency syndrome. the diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. diagnosis of tuberculosis was confirmed by auramine stain, rrna amplification and culture of mycobacterium tuberculosis from synovial fluid of the elbow joint. the patient responded ...201423765512
undetected multidrug-resistant tuberculosis amplified by first-line therapy in mixed infection.infections with >1 mycobacterium tuberculosis strain(s) are underrecognized. we show, in vitro and in vivo, how first-line treatment conferred a competitive growth advantage to amplify a multidrug-resistant m. tuberculosis strain in a patient with mixed infection. diagnostic techniques that identify mixed tubercle bacilli populations are needed to curb the spread of multidrug resistance.201323764343
characterization of dendritic cell and regulatory t cell functions against mycobacterium tuberculosis infection.glutathione (gsh) is a tripeptide that regulates intracellular redox and other vital aspects of cellular functions. gsh plays a major role in enhancing the immune system. dendritic cells (dcs) are potent antigen presenting cells that participate in both innate and acquired immune responses against microbial infections. regulatory t cells (tregs) play a significant role in immune homeostasis. in this study, we investigated the effects of gsh in enhancing the innate and adaptive immune functions o ...201323762843
immune vulnerability of infants to tuberculosis.one of the challenges faced by the infant immune system is learning to distinguish the myriad of foreign but nonthreatening antigens encountered from those expressed by true pathogens. this balance is reflected in the diminished production of proinflammatory cytokines by both innate and adaptive immune cells in the infant. a downside of this bias is that several factors critical for controlling mycobacterium tuberculosis infection are significantly restricted in infants, including tnf, il-1, and ...201323762096
vitamin d induces interleukin-1β expression: paracrine macrophage epithelial signaling controls m. tuberculosis infection.although vitamin d deficiency is a common feature among patients presenting with active tuberculosis, the full scope of vitamin d action during mycobacterium tuberculosis (mtb) infection is poorly understood. as macrophages are the primary site of mtb infection and are sites of vitamin d signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin d, 1,25-dihydroxyvitamin d (1,25d). we found that the virul ...201323762029
exploratory study on plasma immunomodulator and antibody profiles in tuberculosis patients.host immune responses to mycobacterium tuberculosis are generally able to contain infection and maintain a delicate balance between protection and immunopathology. a shift in this balance appears to underlie active disease observed in about 10% of infected individuals. effects of local inflammation, combined with anti-m. tuberculosis systemic immune responses, are directly detectable in peripheral circulation, without ex vivo stimulation of blood cells or biopsy of the affected organs. we studie ...201323761664
consequences of whib7 (rv3197a) mutations in beijing genotype isolates of the mycobacterium tuberculosis complex. 201323761426
rifampin resistance missed in automated liquid culture system for mycobacterium tuberculosis isolates with specific rpob mutations.who-endorsed phenotypic drug susceptibility testing (dst) methods for mycobacterium tuberculosis are assumed to be the gold standard for identifying rifampin (rmp) resistance. however, previous results indicated that low-level, yet probably clinically relevant, rmp resistance linked to specific rpob mutations is easily missed by some growth-based methods. we aimed to compare the level of resistance detected on löwenstein-jensen (lj) medium with resistance detected by the bactec mgit 960 automate ...201323761146
tuberculosis screening using a t-cell interferon-γ release assay in japanese medical students and non-japanese international students.screening of medical students and international students for tuberculosis (tb) at the time of admission is a key strategy to control and prevent the spread of infection on university campus and teaching hospitals because of the high risk of exposure to tb patients. the mycobacterium tuberculosis antigen-specific t-cell interferon-γ release assays (igras) are specific latent tuberculosis detection methods used in such groups. currently, in japan, there are no guidelines and no baseline data on ig ...201323759899
genetic characterization of compensatory evolution in strains carrying rpob ser531leu, the rifampicin resistance mutation most frequently found in clinical isolates.the evolution of rifampicin resistance in mycobacterium tuberculosis is a major threat to effective tuberculosis therapy. much is known about the initial emergence of rifampicin resistance, but the further evolution of these resistant strains has only lately been subject to investigation. although resistance can be caused by many different mutations in rpob, among clinical m. tuberculosis isolates the mutation rpob s531l is overwhelmingly the most frequently found. clinical isolates with rpob s5 ...201323759506
transmission of multidrug-resistant tuberculosis in the usa: a cross-sectional study.multidrug-resistant (mdr) tuberculosis is a potential threat to tuberculosis elimination, but the extent of mdr tuberculosis disease in the usa that is attributable to transmission within the country is unknown. we assessed transmission of mdr tuberculosis and potential contributing factors in the usa.201323759447
the prostaglandin e2 receptor ep4 is integral to a positive feedback loop for prostaglandin e2 production in human macrophages infected with mycobacterium tuberculosis.prostaglandin e2 (pge2) is an important biological mediator involved in the defense against mycobacterium tuberculosis (mtb) infection. previously, we reported that in macrophages (mϕs), infection with avirulent mtb h37ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the pge2 receptor ep2. however, human mϕs also express ep4, a pge2 receptor functionally closely related to ep2 that also couples to stimulatory guanine nucleotide binding pr ...201323759445
kinetic mechanism and energetics of binding of phosphoryl group acceptors to mycobacterium tuberculosis cytidine monophosphate kinase.cytidine monophosphate kinase from mycobacterium tuberculosis (mtcmk) likely plays a role in supplying precursors for nucleic acid synthesis. mtcmk catalyzes the atp-dependent phosphoryl group transfer preferentially to cmp and dcmp. initial velocity studies and isothermal titration calorimetry (itc) measurements showed that mtcmk follows a random-order mechanism of substrate (cmp and atp) binding, and an ordered mechanism for product release, in which adp is released first followed by cdp. the ...201323756762
[introduction of dinitrosyl iron complexes with thiol-containing ligands into animal organism by inhalation method].the possibility of water-soluble dinitrosyl iron complexes (dnic) with thiol-containing ligands introduction into lungs and other tissues of mice by free inhalation of little drops (2-3 microns diameter) of the solutions of these complexes was investigated. little drops of 2-20 mm solutions of the complexes were obtained by using an inhalation apparatus (compressor nebulizer). a cloud of these little drops was then inhaled by animals in a closed chamber. a maximal amount of protein-bound dnics f ...201323755557
frequency of regulatory t-cells in the peripheral blood of patients with pulmonary tuberculosis from shanxi province, china.tuberculosis (tb) is a disease caused by the chronic and continuous infection of the pathogen mycobacterium tuberculosis (m. tuberculosis). m. tuberculosis is an intracellular bacterial pathogen and is eliminated mainly through cd4(+) effector th cells. m. tuberculosis induces regulatory t lymphocytes (tregs) that mediate immune suppression by cell-to-cell contact or by secreting cytokines such as transforming growth factor-β (tgf-β). to understand the role of regulatory t-cells in the pathogene ...201323755239
mycobacterium tuberculosis beijing type mutation frequency--author's response. 201323750367
mycobacterium tuberculosis beijing type mutation frequency. 201323750366
application of hyperbranched rolling circle amplification for direct detection of mycobacterium tuberculosis in clinical sputum specimens.global tuberculosis (tb) control is encumbered by the lack of a rapid and simple detection method for diagnosis, especially in low-resource areas. an isothermal amplification method, hyperbranched rolling circle amplification (hrca), was optimized to detect mycobacterium tuberculosis (mtb) in clinical sputum specimens.201323750210
microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms.macrophages in granulomas are both antimycobacterial effector and host cell for mycobacterium tuberculosis, yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. to address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. macaque granulomas had upregulated inducible and endothelial no synthase (inos and enos) and arginase (arg1 and arg2) expressi ...201323749634
mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis.a key question in tuberculosis control is why some strains of m. tuberculosis are preferentially associated with resistance to multiple drugs. we demonstrate that m. tuberculosis strains from lineage 2 (east asian lineage and beijing sublineage) acquire drug resistances in vitro more rapidly than m. tuberculosis strains from lineage 4 (euro-american lineage) and that this higher rate can be attributed to a higher mutation rate. moreover, the in vitro mutation rate correlates well with the bacter ...201323749189
design and synthesis of biquinolone-isoniazid hybrids as a new class of antitubercular and antimicrobial agents.twenty four biquinolone-isoniazid hybrids were designed based on molecular hybridization technique and synthesized via multicomponent cyclocondensation (mcc) approach. all the newly synthesized compounds were screened for their antimicrobial and antitubercular activities. the brine shrimp bioassay was carried out to study the cytotoxicity of the synthesized compounds. hybrids 7f (mic = 25 μg/ml); 7a, 7e and 7m (mic = 50 μg/ml); 7g, 7h and 7k (mic = 62.5 μg/ml) exhibited excellent antimicrobial a ...201323747804
carbohydrate recognition by rpfb from mycobacterium tuberculosis unveiled by crystallographic and molecular dynamics analyses.resuscitation of mtb is crucial to the etiology of tuberculosis, because latent tuberculosis is estimated to affect one-third of the world population. the resuscitation-promoting factor rpfb is mainly responsible for mtb resuscitation from dormancy. given the impact of latent tuberculosis, rpfb represents an interesting target for tuberculosis drug discovery. however, no molecular models of substrate binding and catalysis are hitherto available for this enzyme. here, we identified key interactio ...201323746526
identification and analysis of mutations in the katg gene in multidrug-resistant mycobacterium tuberculosis clinical isolates.a major role in the development of resistance of mycobacterium tuberculosis to isoniazid (inh) is attributed to mutations in the katg gene coding for the catalase/peroxidase, an enzyme required for obtaining a pharmacologically active form of the drug. analysis of mutations in the katg gene in m. tuberculosis strains may contribute to the development of reliable and rapid tests for detection of inh resistance. the aim of the study was to identify and characterize mutations in the katg gene in mu ...201323744165
functional analysis of the espr binding sites upstream of espr in mycobacterium tuberculosis.the esx-1 secretion system exports substrate proteins into host cells and is crucial for the pathogenesis of mycobacterium tuberculosis. espr is one of the characterized transcriptional regulators that modulates the esx-1 system by binding the conserved espr binding sites in the promoter of espa, the encoding gene of espa, which is also a substrate protein of the esx-1 system and is required for the esx-1 activity. espr is autoregulatory and conserved espr binding sites are present upstream of e ...201323743602
elevated ip-10 and il-6 from bronchoalveolar lavage cells are biomarkers of non-cavitary tuberculosis.active tb disease can destroy lung parenchyma leading to cavities. immune responses that predispose or protect individuals from lung damage during tb are poorly defined.201323743311
sublineages of lineage 4 (euro-american) mycobacterium tuberculosis differ in genotypic clustering.mycobacterium tuberculosis is classified into six phylogenetic lineages, each of which can be divided into sublineages. sublineages of the same lineage have phenotypic differences, including their capacity to cause disease (pathogenicity).201323743309
association between mycobacterium tuberculosis lineage and time to sputum culture conversion.mycobacterium tuberculosis comprises four principal genetic lineages: one evolutionarily ancestral (indo-oceanic) and three modern. whether response to tuberculosis (tb) treatment differs among the lineages is unknown.201323743308
severe pneumonia after intravesical bcg instillation in a patient with invasive bladder cancer: case report and literature review.we present here the case of a 66 year old man with a severe bilateral community acquired pneumonia secondary to dissemination after an intravesical instillation of bacilllus calmette-guerin (bcg). diagnosis was based on positive polymerase chain reaction (pcr) for mycobacterium tuberculosis complex in bronchoalveolar lavage and on the finding on transbronchial biopsy of non necrotising granulomas histopathologically similar to the granulomas found in bladder biopsies. these findings were confirm ...201323741946
molecular epidemiology, drug susceptibility and economic aspects of tuberculosis in mubende district, uganda.tuberculosis (tb) remains a global public health problem whose effects have major impact in developing countries like uganda. this study aimed at investigating genotypic characteristics and drug resistance profiles of mycobacterium tuberculosis isolated from suspected tb patients. furthermore, risk factors and economic burdens that could affect the current control strategies were studied.201323741382
perforated tuberculosis lymphadenitis.a 26-year-old man (human immunodeficiency virus-positive and not taking highly active antiretroviral treatment [haart]) presented to the emergency room with 2 months of malaise, 20 kg weight loss, high spiking fevers, generalized lymph nodes, night sweats, dry cough, and chest pain when swallowing. on physical examination, he had multiple cervical lymphadenopathies. suspecting a systemic opportunistic infection, a contrasted chest computed tomography (ct) was done, showing an esophageal to media ...201323740190
bone tuberculosis: a case report on child.the authors report a case of a 12-year-old child with a complaint of pain and deformity in the lower thoracic region that had lasted for two years. clinical, epidemiological and laboratory characteristics associated with images of apparent damage in the t9-t10 and t11-t12 vertebrae taken by radiography of the thoracic spine and nuclear magnetic resonance in addition to the positivity of the molecular test based on the polymerase chain reaction, led to tuberculous spondylitis being diagnosed and ...201323740070
16 kda heat shock protein from heat-inactivated mycobacterium tuberculosis is a homodimer - suitability for diagnostic applications with specific llama vhh monoclonals.the 16 kda heat shock protein (hsp) is an immuno-dominant antigen, used in diagnosis of infectious mycobacterium tuberculosis (m.tb.) causing tuberculosis (tb). its use in serum-based diagnostics is limited, but for the direct identification of m.tb. bacteria in sputum or cultures it may represent a useful tool. recently, a broad set of twelve 16 kda specific heavy chain llama antibodies (vhh) has been isolated, and their utility for diagnostic applications was explored.201323737964
novel mycobacterium tuberculosis complex isolate from a wild chimpanzee.tuberculosis (tb) is caused by gram-positive bacteria known as the mycobacterium tuberculosis complex (mtbc). mtbc include several human-associated lineages and several variants adapted to domestic and, more rarely, wild animal species. we report an m. tuberculosis strain isolated from a wild chimpanzee in côte d'ivoire that was shown by comparative genomic and phylogenomic analyses to belong to a new lineage of mtbc, closer to the human-associated lineage 6 (also known as m. africanum west afri ...201323735084
dormant mycobacterium tuberculosis fails to block phagosome maturation and shows unexpected capacity to stimulate specific human t lymphocytes.dormancy is defined as a stable but reversible nonreplicating state of mycobacterium tuberculosis. it is currently thought that dormant m. tuberculosis (d-mtb) is responsible for latent tuberculosis (tb) infection. recently, d-mtb was also shown in sputa of patients with active tb, but the capacity of d-mtb to stimulate specific immune responses was not investigated. we observed that purified protein derivative-specific human cd4(+) t lymphocytes recognize mycobacterial ags more efficiently when ...201323733870
analysis of pyroptosis in bacterial infection.eukaryotic cells undergo death by several different mechanisms: apoptosis, a cell death that prevents inflammatory response; necrosis, when the cell membrane lyses and all the intracellular content is spilled outside; and pyroptosis, a cell death that is accompanied by the release of inflammatory cytokines by the dying cells. pyroptosis is designed to attract a nonspecific innate response to the site of infection or tumor. in this chapter, we describe the methods used to study pyroptosis in a ma ...201323733570
prevalence and genetic characterization of second-line drug-resistant and extensively drug-resistant mycobacterium tuberculosis in rural china.this study aimed to investigate the prevalence of resistance to second-line antituberculosis (anti-tb) drugs and its association with resistance-related mutations in mycobacterium tuberculosis isolated in china. in the present study, we collected 380 isolates from a population-based study in china and tested the drug susceptibility to first- and selected second-line drugs. these results were compared with polymorphisms in the dna sequences of genes associated with drug resistance and mic values ...201323733477
potent rifamycin-sparing regimen cures guinea pig tuberculosis as rapidly as the standard regimen.strategies involving new drug combinations, as well as new uses of existing drugs, are urgently needed to reduce the time required to cure patients with drug-sensitive or multidrug-resistant (mdr) tuberculosis (tb). we compared the sterilizing activity of the standard first-line antitubercular regimen, rifampin-isoniazid-pyrazinamide (rhz), with that of the novel regimen pa-824-moxifloxacin-pyrazinamide (pamz), which is currently being studied in clinical trials (nct01498419), in the guinea pig ...201323733473
contribution of spoligotyping and miru-vntrs to characterize prevalent mycobacterium tuberculosis genotypes infecting tuberculosis patients in morocco.in the present study, mycobacterium tuberculosis complex (mtbc) clinical isolates from culture-positive tb patients in morocco were studied by spoligotyping and 12-loci miru-vntr typing methods to characterize prevalent genotypes (n = 219 isolates from 208 patients). spoligotyping resulted in 39 unique patterns and 167 strains in 30 clusters (2-50 strains per cluster). comparison with international database showed that 29 of 39 unique patterns matched existing shared spoligotype international ty ...201423732366
the re-emergence of tuberculosis: what have we learnt from molecular epidemiology?tuberculosis (tb) has re-emerged over the past two decades: in industrialized countries in association with immigration, and in africa owing to the human immunodeficiency virus epidemic. drug-resistant tb is a major threat worldwide. the variable and uncertain impact of tb control necessitates not only better tools (diagnostics, drugs, and vaccines), but also better insights into the natural history and epidemiology of tb. molecular epidemiological studies over the last two decades have contribu ...201323731470
molecular characterization of mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in felege hiwot referral hospital, northwest ethiopia.tuberculosis (tb), caused by the mycobacterium tuberculosis complex (mtbc), is a serious infection in humans and animals. ethiopia is one of the countries in sub-saharan africa with the highest burden of tb. however, limited information is available on the genotypic characteristics of m. tuberculosis strains infecting humans. the objective of the present study was to characterize the mycobacterial species isolated from pulmonary tb patients using molecular typing.201423727395
mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against mycobacterium tuberculosis (m. tb).development of an improved vaccine against tuberculosis (tb) is hindered by the lack of a surrogate of protection. efficacy of new tb vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within tb endemic areas. it is critical that vaccines with the greatest potential to protect are selected for these trials. mycobacterial growth inhibition assays (mgias) have been developed with the hope that these in-vitro functional assays will correlate with protection, wh ...201323726784
sorting inactivated cells using cell-imprinted polymer thin films.previous work showed that cell imprinting in a poly(dimethylsiloxane) film produced artificial receptors to cells by template-assisted rearrangement of functional groups on the surface of the polymer thin film which facilitated cell capture in the polymer surface indentations by size, shape, and, most importantly, chemical recognition. we report here that inactivation of cells by treatment with formaldehyde (4%), glutaraldehyde (2%), or a combination of the two leads to markedly improved capture ...201323725546
highly stereocontrolled total synthesis of β-d-mannosyl phosphomycoketide: a natural product from mycobacterium tuberculosis.β-d-mannosyl phosphomycoketide (c32-mpm), a naturally occurring glycolipid found in the cell walls of mycobacterium tuberculosis, acts as a potent antigen to activate t-cells upon presentation by cd1c protein. the lipid portion of c32-mpm contains a c32-mycoketide, consisting of a saturated oligoisoprenoid chain with five chiral methyl branches. here we develop several stereocontrolled approaches to assemble the oligoisoprenoid chain with high stereopurity (>96%) using julia-kocienski olefinatio ...201323724960
in vitro and in vivo activities of ruthenium(ii) phosphine/diimine/picolinate complexes (scar) against mycobacterium tuberculosis.rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. drugs in this class form part of a 6-month regimen that is ineffective against mdr and xdr tb, and incompatible with many antiretroviral drugs. investments in r&d strategies have increased substantially in the last decades. however, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. ruthenium ...201323724039
purification, crystallization and preliminary x-ray crystallographic studies of the mycobacterium tuberculosis dna gyrase atpase domain.mycobacterium tuberculosis dna gyrase, a nanomachine involved in the regulation of dna topology, is the only type ii topoisomerase present in this organism and hence is the sole target of fluoroquinolones in the treatment of tuberculosis. the atpase domain provides the energy required for catalysis by atp hydrolysis. two constructs corresponding to this 43 kda domain, mtb-gyrb47(c1) and mtb-gyrb47(c2), have been overproduced, purified and crystallized. diffraction data were collected from three ...201323722853
comparison of mycobacterium tuberculosis drug susceptibility using solid and liquid culture in nigeria.this study compares mycobacterium tuberculosis culture isolation and drug sensitivity testing (dst) using solid (lj) and liquid (bactec-mgit-960) media in nigeria.201323721428
rapid diagnosis of mycobacterium tuberculosis infection and drug susceptibility testing.the global control of tuberculosis remains a challenge from the standpoint of diagnosis, detection of drug resistance, and treatment. this is an area of special concern to the health of women and children, particularly in regions of the world with high infant mortality rates and where women have limited access to health care.201323721277
post-menopausal endometrial tuberculosis mimicking carcinoma: an important differential diagnosis to consider.we report the case of a menopausal 74-year-old patient who presents pyorrhoea for 6months. we suspect initially a carcinoma process, but the anatomopathological examination takings obtained by biopsy curettage of the endometrial under hysteroscopy is in favor of an inflammatory infiltrate with epithelioid and giant cells of type langhans and type muller without caseous necrosis. the bacteriological direct examination after coloring of gram, ziehl-neelsen and sabouraud was negative. the bacteriol ...201326785900
predominance of beijing genotype in extensively drug resistant mycobacterium tuberculosis isolates from a tertiary care hospital in new delhi, india.out of a total of 311 mycobacterium tuberculosis isolates from sputum specimens subjected to first- and second-line drug-susceptibility testing (dst) at a hospital serving as a referral center for chronic tuberculosis (tb) cases in new delhi, 232/311 (74.6%) isolates were found to be resistant to isoniazid and rifampicin. among multidrug-resistant (mdr) isolates, 119/232 (51.3%) were resistant to four first-line drugs (streptomycin, isoniazid, rifampicin and ethambutol). mono-resistance to isoni ...201326785898
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