| conjugated and entrapped hpma-pla nano-polymeric micelles based dual delivery of first line anti tb drugs: improved and safe drug delivery against sensitive and resistant mycobacterium tuberculosis. | first line antitb drugs have several physical and toxic manifestations which limit their applications. rif is a hydrophobic drug and has low water solubility and inh is hepatotoxic. the main objective of the study was to synthesize, characterize hpma-pla co-polymeric micelles for the effective dual delivery of inh and rif. | 2017 | 28685299 |
| evaluation of mycotube, a modified version of lowenstein-jensen (lj) medium, for efficient recovery of mycobacterium tuberculosis (mtb). | timely diagnosis of tuberculosis (tb), caused by mycobacterium tuberculosis (mtb), is only achieved for ~58% cases. an improved, accurate, time- and cost-effective method for bacteriological confirmation of mtb is necessary. we evaluated mycotube, a new variant of lowenstein-jensen (lj) culture medium, by comparing it with mycobacterium growth indicator tube (mgit) 960 (gold standard), local lj, and biomérieux lj-t in terms of isolation rate and time-to-growth. pulmonary and extra-pulmonary samp ... | 2017 | 28685188 |
| erratum: data intensive genome level analysis for identifying novel, non-toxic drug targets for multi drug resistant mycobacterium tuberculosis. | this corrects the article doi: 10.1038/srep46595. | 2017 | 28684876 |
| complete genome sequences of three representative mycobacterium tuberculosis beijing family strains belonging to distinct genotype clusters in hanoi, vietnam, during 2007 to 2009. | we present here three complete genome sequences of mycobacterium tuberculosis beijing family strains isolated in hanoi, vietnam. these three strains were selected from major genotypic clusters (15-miru-vntr) identified in a previous population-based study. we emphasize their importance and potential as reference strains in this asian region. | 2017 | 28684565 |
| longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy. | effective treatment of mycobacterium tuberculosis (mtb) infection requires at least 6 months of daily therapy with multiple orally administered antibiotics. although this drug regimen is administered annually to millions worldwide, the impact of such intensive antimicrobial treatment on the host microbiome has never been formally investigated. here, we characterized the longitudinal outcome of conventional isoniazid-rifampin-pyrazinamide (hrz) tb drug administration on the diversity and composit ... | 2017 | 28683818 |
| host-directed therapeutics as novel angle for tuberculosis treatment. | despite significant efforts to improve tuberculosis (tb) treatment, it remains a worldwide infectious disease due to the limitations of current tb regimens. recent work on novel tb treatment strategies has suggested that directly targeting host factors is beneficial for tb treatment. such strategies, termed host-directed therapeutics (hdts), focus on host-pathogen interactions. hdts are more beneficial than existed tb drugs, which are limited the long durations of treatment and the emergence of ... | 2017 | 28683527 |
| proteomics of culture filtrate of prevalent mycobacterium tuberculosis strains: 2d-page map and maldi-tof/ms analysis. | although diverse efforts have been done to identify biomarkers for control of tuberculosis using laboratory strain mycobacterium tuberculosis h37rv, the disease still poses a threat to mankind. there are many emerging m. tuberculosis strains, and proteomic profiling of these strains might be important to find out potential targets for diagnosis and/or prevention of tuberculosis. we evaluated the comparative proteomic profiling of culture filtrate (cf) proteins from prevalent m. tuberculosis stra ... | 2017 | 28683213 |
| synthesis and immunological studies of the lipomannan backbone glycans found on the surface of mycobacterium tuberculosis. | investigations into novel bacterial drug targets and vaccines are necessary to overcome tuberculosis. lipomannan (lm), found on the surface of mycobacterium tuberculosis (mtb), is actively involved in the pathogenesis and survival of mtb. here, we report for the first time a rapid synthesis and biological activities of an lm glycan backbone, α(1-6)mannans. the rapid synthesis is achieved via a regio- and stereoselective ring opening polymerization to generate multiple glycosidic bonds in one sim ... | 2017 | 28682637 |
| synthesis of a 3-amino-2,3-dihydropyrid-4-one and related heterocyclic analogues as mechanism-based inhibitors of bioa, a pyridoxal phosphate-dependent enzyme. | amiclenomycin (acm) is a chemically unstable antibiotic with selective activity against mycobacterium tuberculosis (mtb) due to mechanism-based inhibition of bioa, a pyridoxal 5'-phosphate (plp)-dependent aminotransferase. the first-generation acm analogue dihydro-2-pyridone 1 maintains a similar bioactivation mechanism concluding with covalent labeling of the plp cofactor. to improve on 1, we report the synthesis of dihydro-4-pyranone 2, dihydro-4-pyridone 3, and dihydro-4-thiopyranone 13, whic ... | 2017 | 28682613 |
| development and evaluation of a loop-mediated isothermal amplification combined with au-nanoprobe assay for rapid detection of mycobacterium tuberculosis. | loop-mediated isothermal amplification (lamp) has been proposed as an inexpensive and easy to perform assay for molecular diagnostics. we present a novel strategy for the detection of lamp amplicons derived from mycobacterium tuberculosis by the use of au-nanoprobes. when applied to a total of 93 clinical specimens, the lamp assay demonstrated sensitivity and specificity higher than that of polymerase chain reaction and culture. the au-nanoprobe augmented lamp test platform with its advantages o ... | 2017 | 28681828 |
| levels of circulating immune complexes containing mycobacterium tuberculosis-specific antigens in pulmonary tuberculosis and sarcoidosis patients. | the present study was conducted to understand the aetiological link between tuberculosis (tb) and sarcoidosis. sera from smear-positive tb subjects (n = 24), smear-negative tb subjects (n = 24), sarcoidosis patients (n = 24) and healthy controls (n = 24) were collected and circulating immune complexes were isolated. sandwich elisa was performed for detecting four highly specific mycobacterial regions of difference (rd) proteins (early secretory antigenic target 6 [esat6], 10 kda culture filtrate ... | 2017 | 28681824 |
| genotypic characterisation of mycobacterium tuberculosis isolates from tuberculous meningitis patients at a tertiary neurocare centre in southern india. | specific genotypes of mycobacterium tuberculosis (mtb) have been reported to cause outbreaks of pulmonary tuberculosis (tb) in geographical areas that are endemic to tb. however, since there is little epidemiological evidence on the association of particular genotypes that cause tuberculous meningitis (tbm), we sought to investigate the association of specific mtb strains with infection of the central nervous system (cns). | 2017 | 28681808 |
| disruption of key nadh-binding pocket residues of the mycobacterium tuberculosis inha affects dd-coa binding ability. | tuberculosis (tb) is a global health problem that affects over 10 million people. there is an urgent need to develop novel antimicrobial therapies to combat tb. to achieve this, a thorough understanding of key validated drug targets is required. the enoyl reductase inha, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-tb drug isoniazid. to better understand the activity of this protein a series of mutants, targeted to the ... | 2017 | 28680153 |
| virtual screening, pharmacophore development and structure based similarity search to identify inhibitors against ider, a transcription factor of mycobacterium tuberculosis. | ider, an essential gene of mycobacterium tuberculosis, is an attractive drug target as its conditional knockout displayed attenuated growth phenotype in vitro and in vivo. to the best of our knowledge, no inhibitors of ider are identified. we carried out virtual screening of nci database against the ider dna binding domain followed by inhibition studies using emsa. nine compounds exhibited potent inhibition with nsc 281033 (i-20) and nsc 12453 (i-42) exhibiting ic50 values of 2 µg/ml and 1 µg/ml ... | 2017 | 28680150 |
| mechanism-based inactivator of isocitrate lyases 1 and 2 from mycobacterium tuberculosis. | isocitrate lyase (icl, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for mycobacterium tuberculosis (mtb) during the persistent phase of human tb infection. here, we report 2-vinyl-d-isocitrate (2-vic) as a mechanism-based inactivator of mtb icl1 and icl2. the enzyme-catalyzed retro-aldol cleavage of 2-vic unmasks a michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site cys191 2-vic disp ... | 2017 | 28679637 |
| orbital tuberculosis: clinicopathological correlation and diagnosis using pcr in formalin-fixed tissues. | this article describes the clinicopathological correlation and challenges encountered in the diagnosis of orbital tuberculosis (tb). retrospective, interventional case series. a chart review of six patients who underwent biopsy for an orbital mass between january 2012 and december 2013 was performed. institutional review board approval was obtained for the study. clinical, radiological, and laboratory findings were documented, and response to antitubercular therapy (att) was noted. age at presen ... | 2017 | 28678592 |
| hla-e presents glycopeptides from the mycobacterium tuberculosis protein mpt32 to human cd8(+) t cells. | infection with mycobacterium tuberculosis (mtb), the bacterium that causes tuberculosis, remains a global health concern. both classically and non-classically restricted cytotoxic cd8(+) t cells are important to the control of mtb infection. we and others have demonstrated that the non-classical mhc i molecule hla-e can present pathogen-derived peptides to cd8(+) t cells. in this manuscript, we identified the antigen recognized by an hla-e-restricted cd8(+) t cell clone isolated from an mtb late ... | 2017 | 28676677 |
| the sigma factor sigd of mycobacterium tuberculosis putatively enhances gene expression of the septum site determining protein under stressful environments. | this work examined the expression of the septum site determining gene (ssd) of mycobacterium tuberculosis cdc1551 and its δsigd mutant under different growing conditions. the results showed an up-regulation of ssd during stationary phase and starvation conditions, but not during in vitro dormancy, suggesting a putative role for sigd in the control of ssd expression mainly under lack-of-nutrients environments. furthermore, we elucidated a putative link between ssd expression and cell elongation o ... | 2017 | 28675242 |
| genexpert technology. a breakthrough for the diagnosis of tuberculous pericarditis and pleuritis in less than 2 hours. | to evaluate the diagnostic validity of genexpert for the detection of mycobacterium tuberculosis (mtb) in pericardial and pleural effusions samples. | 2017 | 28674714 |
| mycobacterium tuberculosis endocarditis in native valves. | | 2017 | 28674587 |
| comparison of laboratory testing methods for the diagnosis of tuberculous pleurisy in china. | to evaluate the diagnostic utilities of different methods for mycobacterium tuberculosis (m. tuberculosis) detection in pleural fluid that represent potentially cost-effective measures for resource-limited settings in china. we compared diagnostic characteristics of the ampsure simultaneous amplification and testing method, the bactec mgit 960 system, and acid-fast bacilli staining of specimen smears for detection of m. tuberculosis in pleural fluids of 438 patients with suspected tuberculous pl ... | 2017 | 28674427 |
| a novel 6-benzyl ether benzoxaborole is active against mycobacterium tuberculosis in vitro. | we identified a novel 6-benzyl ether benzoxaborole with potent activity against mycobacterium tuberculosis the compound had an mic of 2 μm in liquid medium. the compound was also able to prevent growth on solid medium at 0.8 μm and was active against intracellular bacteria (50% inhibitory concentration [ic50] = 3.6 μm) without cytotoxicity against eukaryotic cells (ic50 > 100 μm). we isolated resistant mutants (mic ≥ 100 μm), which had mutations in rv1683, rv3068c, and rv0047c. | 2017 | 28674058 |
| rare presentation of intractable tuberculous panophthalmitis with intraocular and intraorbital abscesses: a case report. | we report a rare presentation of extrapulmonary tuberculosis. | 2017 | 28673337 |
| crystallographic and solution structure of the n-terminal domain of the rel protein from mycobacterium tuberculosis. | modulation of intracellular guanosine 3',5'-bispyrophosphate ((p)ppgpp) level, the effector of the stringent response, is crucial for survival as well as optimal growth of prokaryotes and, thus, for bacterial pathogenesis and dormancy. in mycobacterium tuberculosis (mtb), (p)ppgpp synthesis and degradation are carried out by the bifunctional enzyme mtrel, which consists of 738 residues, including an n-terminal hydrolase- and synthetase-domain (n-terminal domain or ntd) and a c-terminus with a ri ... | 2017 | 28672070 |
| epidemiology of musculoskeletal tuberculosis in an area with high disease prevalence. | retrospective observational study. | 2017 | 28670408 |
| an unusual triad of hemophagocytic syndrome, lymphoma and tuberculosis in a non-hiv patient. | background lymphoma complicated with hemophagocytic syndrome and tuberculosis has been rarely reported. the clinical and radiological presentation of these potentially fatal conditions can be easily confused and there is a potential for misdiagnosis. case report we present a 58-year-old hispanic female who was admitted to the hospital with dizziness and fever. her initial admission diagnosis was severe sepsis secondary to community acquired pneumonia. she was started on intravenous antibiotics. ... | 2017 | 28669977 |
| investigation of pre-xdr beijing mycobacterium tuberculosis transmission to a healthcare worker in france, 2016. | a case of occupational contamination of a healthcare worker by a pre-extensively drug-resistant (pre-xdr) beijing strain of mycobacterium tuberculosis at the university hospital of montpellier, france is reported. the index case was identified using genetic fingerprinting of isolates. this report underscores the risk of healthcare-associated contamination by pre-xdr tuberculosis (tb) in low-incidence countries and the importance of molecular tools for tb care. it also calls for increased vigilan ... | 2017 | 28669673 |
| development of a novel lead that targets m. tuberculosis polyketide synthase 13. | widespread resistance to first-line tb drugs is a major problem that will likely only be resolved through the development of new drugs with novel mechanisms of action. we have used structure-guided methods to develop a lead molecule that targets the thioesterase activity of polyketide synthase pks13, an essential enzyme that forms mycolic acids, required for the cell wall of mycobacterium tuberculosis. our lead, tam16, is a benzofuran class inhibitor of pks13 with highly potent in vitro bacteric ... | 2017 | 28669536 |
| high incidence of fluoroquinolone resistance and effect of efflux pump inhibitors on moxifloxacin resistance among mycobacterium tuberculosis isolates causing urinary tract infection in taiwan. | this study explored the prevalence of urinary tract tuberculosis (utb) and whether efflux pump activation accounts for resistance to moxifloxacin in taiwan. of 3034 patients with culture-confirmed tb from 2005-2012, 47 patients (1.5%) with utb were included in this study. minimum inhibitory concentrations (mics) of moxifloxacin were determined in the presence and absence of efflux pump inhibitors (epis), including verapamil, reserpine and carbonyl cyanide 3-chlorophenylhydrazone (cccp). epi resp ... | 2017 | 28668684 |
| cross-linking of dicyclotyrosine by the cytochrome p450 enzyme cyp121 from mycobacterium tuberculosis proceeds through a catalytic shunt pathway. | cyp121, the cytochrome p450 enzyme in mycobacterium tuberculosis that catalyzes a single intramolecular c-c cross-linking reaction in the biosynthesis of mycocyclosin, is crucial for the viability of this pathogen. this c-c coupling reaction represents an expansion of the activities carried out by p450 enzymes distinct from oxygen insertion. although the traditional mechanism for p450 enzymes has been well studied, it is unclear whether cyp121 follows the general p450 mechanism or uses a differe ... | 2017 | 28667013 |
| genomic epidemiology of a major mycobacterium tuberculosis outbreak: retrospective cohort study in a low-incidence setting using sparse time-series sampling. | since 1992, denmark has documented the largest outbreak of tuberculosis in scandinavia ascribed to a single genotype, termed c2/1112-15. as of spring 2017, the international reference laboratory of mycobacteriology in copenhagen has collected and identified isolates from more than a thousand cases belonging to this outbreak via routine mycobacterial interspersed repetitive units-variable number of tandem repeats typing. here, we present a retrospective analysis of the c2/1112-15 dataset, based o ... | 2017 | 28666374 |
| quaternary structure is an essential component that contributes to the sophisticated allosteric regulation mechanism in a key enzyme from mycobacterium tuberculosis. | the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (dah7ps), adopts a range of distinct allosteric regulation mechanisms in different organisms, related to different quaternary assemblies. dah7ps from mycobacterium tuberculosis (mtudah7ps) is a homotetramer, with the allosteric sites in close proximity to the interfaces. here we examine the importance of the quaternary structure on catalysis and regulation, by amino acid substitution targeting the tet ... | 2017 | 28665948 |
| polymerase chain reaction and its correlation with clinical features and treatment response in tubercular uveitis. | correlation of results of polymerase chain reaction for mycobacterium tuberculosis (mtb pcr) with clinical features and treatment response in tubercular uveitis. | 2017 | 28665743 |
| biochemical investigation of rv3404c from mycobacterium tuberculosis. | the causative agent of tuberculosis, mycobacterium tuberculosis, is a bacterium with a complex cell wall and a complicated life cycle. the genome of m. tuberculosis contains well over 4000 genes thought to encode proteins. one of these codes for a putative enzyme referred to as rv3404c, which has attracted research attention as a potential virulence factor for over 12 years. here we demonstrate that rv3404c functions as a sugar n-formyltransferase that converts dtdp-4-amino-4,6-dideoxyglucose in ... | 2017 | 28665588 |
| cd1b-mycolic acid tetramers demonstrate t-cell fine specificity for mycobacterial lipid tails. | mycobacterium tuberculosis synthesizes a thick cell wall comprised of mycolic acids (ma), which are foreign antigens for human t cells. t-cell clones from multiple donors were used to determine the fine specificity of ma recognition by human αβ t cells. most cd1-presented lipid antigens contain large hydrophilic head groups comprised of carbohydrates or peptides that dominate patterns of t-cell specificity. ma diverges from the consensus antigen motif in that it lacks a head group. using multipl ... | 2017 | 28665555 |
| plant-derived antimicrobials to fight against multi-drug-resistant human pathogens. | antibiotic resistance is becoming a pivotal concern for public health that has accelerated the search for new antimicrobial molecules from nature. numbers of human pathogens have inevitably evolved to become resistant to various currently available drugs causing considerable mortality and morbidity worldwide. it is apparent that novel antibiotics are urgently warranted to combat these life-threatening pathogens. in recent years, there have been an increasing number of studies to discover new bio ... | 2017 | 28660459 |
| incidental unilateral tuberculous sacroiliitis detected by (18)f-fdg pet/ct in a patient with abdominal tuberculosis. | tuberculosis is a systemic disease which involves skeletal and articular system very rarely. osteoarticular tuberculosis commonly occurs in the vertebral column and more rarely in the sacroiliac joints. in this study, we report a 44-years-old male patient with low-grade fever, malabsorption syndrome, abdominal and pelvic ascites and low-back pain, that underwent (18)f-fdg pet/ct for identifying the cause of signs and symptoms after a negative abdominal ct and negative thorax radiography. the stu ... | 2017 | 28660225 |
| rna profiling analysis of the serum exosomes derived from patients with active and latent mycobacterium tuberculosis infection. | tuberculosis (tb) has exceeded hiv as the most lethal infectious disease globally for two consecutive years. moreover, one third of the world's population is estimated to have latent tuberculosis infection (ltbi). this is mainly because of difficulties associated with diagnosis and treatment for both tb and ltbi patients. exosomes provide a promising research tool for tb diagnosis and treatment because they are released from various cells containing valuable biochemical information related to di ... | 2017 | 28659881 |
| bioa mutant of mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs. | owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the bacillus calmette-guérin (bcg) vaccine, a more efficient vaccine than bcg is required for the global control of tuberculosis. a number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. in this study, we demonstrate that a bioa mutant ... | 2017 | 28658275 |
| molecular modeling studies and anti-tb activity of trisubstituted indolizine analogues; molecular docking and dynamic inputs. | a series of trisubstituted indolizine analogues has been designed as a result of a fragment-based approach to target the inhibition of mycobacterial enoyl-acyl carrier protein reductase. anti-tuberculosis (tb) screening of the characterized compounds by a resazurin microplate assay method revealed that ethyl group at second position of indolizine nucleus exhibited activity against susceptible and multidrug-resistant strains of mycobacterium tuberculosis at concentration of 5.5 and 11.3 μg/ml, re ... | 2017 | 28657441 |
| determination of redox sensitivity in structurally similar biological redox sensors. | redox stimuli govern a variety of biological processes. the relative sensitivity of redox sensors plays an important role in providing a calibrated response to environmental stimuli and cellular homeostasis. this cellular machinery plays a crucial role in the human pathogen mycobacterium tuberculosis as it encounters diverse microenvironments in the host. the redox sensory mechanism in m. tuberculosis is governed by two component and one-component systems, alongside a class of transcription fact ... | 2017 | 28657321 |
| assessing pharmacodynamic interactions in mice using the multistate tuberculosis pharmacometric and general pharmacodynamic interaction models. | the aim of this study was to investigate pharmacodynamic interactions in mice infected with mycobacterium tuberculosis using population pharmacokinetics, the multistate tuberculosis pharmacometric (mtp) model, and the general pharmacodynamic interaction (gpdi) model. rifampicin, isoniazid, ethambutol or pyrazinamide were administered in monotherapy for 4 weeks. rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide ... | 2017 | 28657202 |
| role of esat-6 in renal injury by regulating microrna-155 expression via tlr4/myd88 signaling pathway in mice with mycobacterium tuberculosis infection. | the study aims to investigate the underlying mechanism involved in the early secretory antigenic target-6 (esat-6) in renal injury through regulation of the expression of mir-155 through the oll-like receptor (tlr)-4 (tlr4)/myeloid differentiation factor 88 (myd88) signaling pathway in mycobacterium tuberculosis (mtb)-infected mice. sixty c57bl/6 mice with mtb-induced renal injury were randomly assigned into control, mtb, mimic, inhibitor, inhibitor + esat6, and inhibitor + esat6 + tak242 groups ... | 2017 | 28655852 |
| identification of host proteins predictive of early stage mycobacterium tuberculosis infection. | the objective of this study was to identify blood-based protein biomarkers of early stage mycobacterium tuberculosis (mtb) infection. we utilized plasma and serum specimens from tb patients and their contacts (age≥12) enrolled in a household contact study in uganda. in the discovery phase cross-sectional samples from 104 hiv-uninfected persons classified as either active tb, latent mtb infection (ltbi), tuberculin skin test (tst) converters, or persistent tst-negative were analyzed. two hundred ... | 2017 | 28655597 |
| preparation and evaluation of potent pentafluorosulfanyl-substituted anti-tuberculosis compounds. | the global fight to stop tuberculosis (tb) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. to bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (sf5 ) compounds which were screened for their activity against mycobacterium tuberculosis (mtb) h37rv in three different assay conditions and media. all eight compounds had sub-micromolar potency, and four di ... | 2017 | 28654200 |
| rifampicin-resistant mycobacterium tuberculosis among tuberculosis-presumptive cases at university of gondar hospital, northwest ethiopia. | various studies have reported that the emergence of drug-resistant tuberculosis poses a significant threat to tuberculosis-control programs worldwide. rifampicin resistance is a surrogate marker of multidrug-resistant tuberculosis, since it reveals the presence of greater than 90% isoniazid resistance. evidence on rifampicin-resistant mycobacterium tuberculosis is scarce in the literature. | 2017 | 28652786 |
| exploiting the synthetic lethality between terminal respiratory oxidases to kill mycobacterium tuberculosis and clear host infection. | the recent discovery of small molecules targeting the cytochrome bc1 :aa3 in mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. the mycobacterial cytochrome bc1 :aa3 consists of a menaquinone:cytochrome c reductase (bc1 ) and a cytochrome aa3 -type oxidase. the clinical-stage drug candidate q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. despite the affinity of q203 for the bc1 :a ... | 2017 | 28652330 |
| il-6 and il-18 cytokine gene variants of pulmonary tuberculosis patients with co-morbid diabetes mellitus and their household contacts in hyderabad. | association of cytokine genes reflects their susceptibility towards infection and disease in household contacts (hhc) of pulmonary tuberculosis (ptb) patients. hyperglycemia, a common factor in diabetics might influence their risk towards mycobacterium tuberculosis infection and disease development. this study determines the association of il-6 and il-18 cytokine gene variants of tb patients with diabetes mellitus (tbdm) and their hhc in hyderabad. | 2017 | 28652186 |
| [identification and evaluation of t cell epitopes of rv0585c from mycobacterium tuberculosis]. | objective: to investigate the human t cell epitopes of mycobacterium (m.) tuberculosis rv0585c protein antigen and their immunogenicity and provide evidence for the development of specific tuberculosis immune diagnostic techniques and tuberculosis vaccine. methods: we synthesized peptides from m. tuberculosis rv0585c protein antigen predicted by te-predict and iedb human t cell epitope prediction tool. the cellular immunoreactivity of the predicted peptides was evaluated through elispot assay wi ... | 2017 | 28651408 |
| the n-terminal domain of mycobacterium tuberculosis ppe17 (rv1168c) protein plays a dominant role in inducing antibody responses in active tb patients. | the ppe (proline-proline-glutamic acid) proteins of mycobacterium tuberculosis are characterized by a conserved n-terminal domain of approximately 180 amino acids and variable c-terminal domain. since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (tb) as they act as a source of antigenic variation. we have demonstrated earlier that one of the ppe proteins ppe17 (rv1168c) induces strong b-cell and t-cell responses in active tb disease and also displa ... | 2017 | 28651002 |
| whole transcriptomic and proteomic analyses of an isogenic m. tuberculosis clinical strain with a naturally occurring 15 kb genomic deletion. | tuberculosis remains one of the most difficult to control infectious diseases in the world. many different factors contribute to the complexity of this disease. these include the ability of the host to control the infection which may directly relate to nutritional status, presence of co-morbidities and genetic predisposition. pathogen factors, in particular the ability of different mycobacterium tuberculosis strains to respond to the harsh environment of the host granuloma, which includes low ox ... | 2017 | 28650996 |
| [discriminatory power of variable number on tandem repeats loci for genotyping mycobacterium tuberculosis strains in china]. | objective: using the standard genotype method, variable number of tandem repeats (vntr), we constructed a vntr database to cover all provinces and proposed a set of optimized vntr loci combinations for each province, in order to improve the preventive and control programs on tuberculosis, in china. methods: a total of 15 loci vntr was used to analyze 4 116 mycobacterium tuberculosis strains, isolated from national survey of drug resistant tuberculosis, in 2007. hunter-gaston index (hgi) was also ... | 2017 | 28647985 |
| antimicrobial investigation of selected soil actinomycetes isolated from unexplored regions of kashmir himalayas, india. | the aim of the present study was to isolate and evaluate the antimicrobial potential of soil actinomycetes of kashmir himalayas. the secondary metabolites of actinomycetes are the prominent source of antibiotics. a total of 121 morphologically different actinomycete strains were isolated and screened for antimicrobial activity against various human pathogens. the ethyl acetate extract of fermented broth an actinomycete strain, identified as streptomyces pratensis exhibited significant antimicrob ... | 2017 | 28647504 |
| drug-resistant tuberculosis - primary transmission and management. | the dots strategy assisted global tuberculosis (tb) control, but was unable to prevent the emergence and spread of drug-resistant strains. genomic evidence confirms the transmission of drug-resistant mycobacterium tuberculosis strains in many different settings, indicative of epidemic spread. these findings emphasise the need for enhanced infection control measures in health care and congregate settings. young children in tb endemic areas are particularly vulnerable. although advances in tb drug ... | 2017 | 28646952 |
| ifnγ-producing cd4(+) t lymphocytes: the double-edged swords in tuberculosis. | ifnγ-producing cd4(+) t cells (ifnγ(+)cd4(+) t cells) are the key orchestrators of protective immunity against mycobacterium tuberculosis (mtb). primarily, these cells act by enabling mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (rnis), and activate autophagy pathways. however, tb is a heterogeneous disease and a host of clinical and experimental findings has also implicated ifnγ(+)cd4(+) t cells in tb pathogenesis. high frequency of ifnγ ... | 2017 | 28646367 |
| monocyte adhesion, migration, and extracellular matrix breakdown are regulated by integrin αvβ3 in mycobacterium tuberculosis infection. | in tuberculosis (tb), the innate inflammatory immune response drives tissue destruction, morbidity, and mortality. monocytes secrete matrix metalloproteinases (mmps), which have key roles in local tissue destruction and cavitation. we hypothesized that integrin signaling might regulate monocyte mmp secretion in pulmonary tb during cell adhesion to the extracellular matrix (ecm). adhesion to type i collagen and fibronectin by mycobacterium tuberculosis-stimulated monocytes increased mmp-1 gene ex ... | 2017 | 28646039 |
| mycobacterium tuberculosis glyceraldehyde-3-phosphate dehydrogenase (gapdh) functions as a receptor for human lactoferrin. | iron is crucial for the survival of living cells, particularly the human pathogen mycobacterium tuberculosis (m.tb) which uses multiple strategies to acquire and store iron. m.tb synthesizes high affinity iron chelators (siderophores), these extract iron from host iron carrier proteins such as transferrin (tf) and lactoferrin (lf). recent studies have revealed that m.tb may also relocate several housekeeping proteins to the cell surface for capture and internalization of host iron carrier protei ... | 2017 | 28642848 |
| role of bacterioferritin & ferritin in m. tuberculosis pathogenesis and drug resistance: a future perspective by interactomic approach. | tuberculosis is caused by mycobacterium tuberculosis, one of the most successful and deadliest human pathogen. aminoglycosides resistance leads to emergence of extremely drug resistant strains of m. tuberculosis. iron is crucial for the biological functions of the cells. iron assimilation, storage and their utilization is not only involved in pathogenesis but also in emergence of drug resistance strains. we previously reported that iron storing proteins (bacterioferritin and ferritin) were found ... | 2017 | 28642844 |
| mcl plays an anti-inflammatory role in mycobacterium tuberculosis-induced immune response by inhibiting nf-κb and nlrp3 inflammasome activation. | mycobacterium tuberculosis (mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (tb). micheliolide (mcl), a sesquiterpene lactone, was recently reported to have a function of relieving lps-induced inflammatory response, but the regulative role of mcl on the immunopathology of tb still remains unknown. in this experiment, we examined the inhibitory effect of mcl on mtb-induced inflammatory respo ... | 2017 | 28642632 |
| identifying mechanisms driving formation of granuloma-associated fibrosis during mycobacterium tuberculosis infection. | mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), is a pulmonary pathogen of major global concern. a key feature of mtb infection in primates is the formation of granulomas, dense cellular structures surrounding infected lung tissue. these structures serve as the main site of host-pathogen interaction in tb, and thus to effectively treat tb we must clarify mechanisms of granuloma formation and their function in disease. fibrotic granulomas are associated with both good ... | 2017 | 28642013 |
| diagnostic performance of the genotype mtbdrplus and mtbdrsl assays to identify tuberculosis drug resistance in eastern china. | the who recently has recommended the genotype mtbdrplus version 1.0 and mtbdrsl version 1.0 assays for widespread use in countries endemic with drug-resistant tuberculosis. despite this, these assays have rarely been evaluated in china, where the burden of drug-resistant tuberculosis is among the highest globally. | 2017 | 28639565 |
| identifying specificity groups in the t cell receptor repertoire. | t cell receptor (tcr) sequences are very diverse, with many more possible sequence combinations than t cells in any one individual. here we define the minimal requirements for tcr antigen specificity, through an analysis of tcr sequences using a panel of peptide and major histocompatibility complex (pmhc)-tetramer-sorted cells and structural data. from this analysis we developed an algorithm that we term gliph (grouping of lymphocyte interactions by paratope hotspots) to cluster tcrs with a high ... | 2017 | 28636589 |
| insights into integrated lead generation and target identification in malaria and tuberculosis drug discovery. | new, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. however, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. ... | 2017 | 28636311 |
| molecular quantum similarity, chemical reactivity and database screening of 3d pharmacophores of the protein kinases a, b and g from mycobacterium tuberculosis. | mycobacterium tuberculosis remains one of the world's most devastating pathogens. for this reason, we developed a study involving 3d pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases a, b, and g. this theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberc ... | 2017 | 28635627 |
| biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in actinobacteria. | a putative lipopeptide biosynthetic gene cluster is conserved in many species of actinobacteria, including mycobacterium tuberculosis and m. marinum, but the specific function of the encoding proteins has been elusive. using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (inlps) through a thio-template mechanism. the biosynthesis features the g ... | 2017 | 28634299 |
| household food insecurity is associated with low interferon-gamma levels in pregnant indian women. | over 20% of tuberculosis (tb) cases during pregnancy occur in india. | 2017 | 28633705 |
| how should discordance between molecular and growth-based assays for rifampicin resistance be investigated? | molecular tests to detect the presence of mycobacterium tuberculosis and genetic polymorphisms in the rpob gene conferring resistance to rifampicin (rmp) have become integral parts of tuberculosis diagnostics worldwide. these assays are often performed sequentially or in parallel to phenotypic drug susceptibility testing. discordances between molecular and phenotypic tests invariably occur. root causes range from pre-, post- and analytic errors to co-existence of non-tuberculous mycobacteria, si ... | 2017 | 28633695 |
| identification of specific antibodies against the ag85c-mpt51-hspx fusion protein (cmx) for serological screening of tuberculosis in endemic area. | development of new tools for rapid and accurate diagnosis of tuberculosis (tb) is considered a strategy for controlling the disease. the recombinant cmx fusion protein is composed of immunodominant epitopes of the ag85c (rv0129c), mpt51 (rv3803c) and the entire hspx (rv2031c) proteins from mycobacterium tuberculosis h37rv (mtb). the aim of this study was to evaluate the applicability of a test using the cmx protein in individuals suspected of tb. | 2017 | 28633546 |
| tailored-pharmacophore model to enhance virtual screening and drug discovery: a case study on the identification of potential inhibitors against drug-resistant mycobacterium tuberculosis (3r)-hydroxyacyl-acp dehydratases. | virtual screening (vs) is powerful tool in discovering molecular inhibitors that are most likely to bind to drug targets of interest. herein, we introduce a novel vs approach, so-called 'tailored-pharmacophore', in order to explore inhibitors that overcome drug resistance. methodology & results: the emergence and spread of drug resistance strains of tuberculosis is one of the most critical issues in healthcare. a tailored-pharmacophore approach was found promising to identify in silico predicted ... | 2017 | 28632406 |
| evaluation of the genotype mtbdrsl test for detection of second-line drug resistance in drug-resistant mycobacterium tuberculosis strains in myanmar. | | 2017 | 28631943 |
| multidrug-resistant tuberculosis detection and characterization of mutations in mycobacterium tuberculosis by genotype mtbdrplus. | detection of drug resistance in mycobacterium tuberculosis by conventional phenotypic drug susceptibility testing methods requires several weeks. therefore, molecular diagnostic tests for rapid detection of multidrug resistance tuberculosis (mdr-tb) are urgently needed. early diagnosis helps in initiating optimal treatment which would not only enable cure of an individual patient but also will curb the transmission of drug resistance in the community. line probe assay (lpa) has shown great promi ... | 2017 | 28631643 |
| a multinational analysis of mutations and heterogeneity in pzase, rpsa, and pand associated with pyrazinamide resistance in m/xdr mycobacterium tuberculosis. | pyrazinamide (pza) is an important first-line drug in all existing and new tuberculosis (tb) treatment regimens. pza-resistance in m. tuberculosis is increasing, especially among m/xdr cases. noted issues with pza drug susceptibility testing (dst) have driven the search for alternative tests. this study provides a comprehensive assessment of pza molecular diagnostics in m/xdr tb cases. a set of 296, mostly xdr, clinical m. tuberculosis isolates from four countries were subjected to dst for eight ... | 2017 | 28630430 |
| impact of gyrb and eis mutations in improving detection of second-line-drug resistance among mycobacterium tuberculosis isolates from georgia. | the country of georgia has a high burden of multi- and extensively drug-resistant tuberculosis (xdr-tb). to evaluate whether mutations in gyrb and eis genes increased the sensitivity of detection of phenotypic resistance to ofloxacin and kanamycin or capreomycin compared to use of the first-generation mtbdrsl assay alone, which tests for mutations in gyra and rrs genes, a retrospective study of stored mycobacterium tuberculosis isolates was performed. all isolates underwent dna sequencing of res ... | 2017 | 28630205 |
| bactericidal and sterilizing activity of a novel regimen with bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. | new regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (tb), including drug-resistant forms. prior studies showed that the novel combinations of bedaquiline (bdq) plus pretomanid (pmd) plus pyrazinamide (pza) and pmd plus moxifloxacin (mxf) plus pza shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine tb model. these 3-drug comb ... | 2017 | 28630203 |
| pyrazinamide susceptibility and pnca mutation profiles of mycobacterium tuberculosis among multidrug-resistant tuberculosis patients in bangladesh. | pyrazinamide (pza) is a frontline antituberculosis (anti-tb) drug used in both first- and second-line treatment regimens. however, due to complex laboratory requirements, the pza susceptibility test is rarely performed, leading to a scarcity of data on susceptibility to pza. bangladesh is a country with a burden of high rates of both tb and multidrug-resistant tb (mdr-tb), but to our knowledge, published data on rates of pza susceptibility (pza(s)), especially among mdr-tb patients, are limited. ... | 2017 | 28630193 |
| molecular detection methods of resistance to antituberculosis drugs in mycobacterium tuberculosis. | molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. we aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among mycobacterium tuberculosis strains. | 2017 | 28629614 |
| drug development against tuberculosis: impact of alkaloids. | despite of the advances made in the treatment and management, tuberculosis (tb) still remains one of main public health problem. the contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of m. tuberculosis. extensive applications of alkaloids in the field ... | 2017 | 28628823 |
| a chromosome 5q31.1 locus associates with tuberculin skin test reactivity in hiv-positive individuals from tuberculosis hyper-endemic regions in east africa. | one in three people has been infected with mycobacterium tuberculosis (mtb), and the risk for mtb infection in hiv-infected individuals is even higher. we hypothesized that hiv-positive individuals living in tuberculosis-endemic regions who do not get infected by mycobacterium tuberculosis are genetically resistant. using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 hiv-posi ... | 2017 | 28628665 |
| systematic review on the proteomic profile of mycobacterium tuberculosis exposed to drugs. | the authors present an overview about proteomics studies in mycobacterium tuberculosis exposed to some anti-tuberculosis drugs and new candidates, using two-dimensional gel electrophoresis and mass spectrometry. to date, that the authors have knowledge, this is the first studies that was performed specifically in m. tuberculosis using systematic review on electronic literature conducted in three databases using the following search terms: tuberculosis or mycobacterium tuberculosis, proteome or p ... | 2017 | 28627738 |
| release characteristics of bone‑like hydroxyapatite/poly amino acid loaded with rifapentine microspheres in vivo. | bone-like hydroxyapatite/poly amino acid (bha/paa) is a potential bone repair material. rifapentine-loaded poly(lactic‑co‑glycolic acid) microspheres (rpms) are bioactive and efficient controlled‑release delivery systems used in vitro. the aim of the present study was to investigate the in vivo drug release characteristics of rpm‑loaded bha/paa on a rabbit model of bone defect. rpm was combined with bha/paa to obtain the drug‑loaded, slow‑releasing bioactive material. bone defects were generated ... | 2017 | 28627673 |
| concomitant mycobacterium tuberculosis infection promotes lung tumor growth through enhancing treg development. | lung cancer is the most common malignancy in humans. an increased population of cd4+foxp3+ regulatory t cells (tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. the exact role and the involved mechanisms of concomitant h37rv infection in non-small cell lung cancer (nsclc) development are still not clear. here, we showed that h37rv infection promoted nsclc cell growth with a higher percentage of tregs found in draining lymph nodes. we also determine ... | 2017 | 28627635 |
| high diversity of multidrug-resistant mycobacterium tuberculosis central asian strain isolates in nepal. | tuberculosis (tb) caused by mycobacterium tuberculosis (mtb) poses a major public health problem in nepal. although it has been reported as one of the dominant genotypes of mtb in nepal, little information on the central asian strain (cas) family is available, especially isolates related to multidrug resistance (mdr) cases. this study aimed to elucidate the genetic and epidemiological characteristics of mdr cas isolates in nepal. | 2017 | 28627432 |
| evaluation of the quantamatrix multiplexed assay platform system for simultaneous detection of mycobacterium tuberculosis and the rifampicin resistance gene using cultured mycobacteria. | the differentiation of mycobacterium tuberculosis complex (mtbc) from non-tuberculous mycobacteria (ntm) is of primary importance for infection control and the selection of anti-tuberculosis drugs. up to date data on rifampicin (rif)-resistant tuberculosis (tb) is essential for the early management of multidrug-resistant tb. the aim of this study was to evaluate the usefulness of a newly developed multiplexed, bead-based bioassay (quantamatrix multiplexed assay platform, qmap) for the rapid diff ... | 2017 | 28627431 |
| identification of better pharmacokinetic benzothiazinone derivatives as new antitubercular agents. | a series of new 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one(btz) derivatives containing a c-2 nitrogen spiro-heterocycle moiety based on the structures of btz candidates btz043 and pbtz169 were designed and synthesized as new antitubercular agents. many of them were found to have excellent in vitro activity (mic < 0.15 μm) against the drug susceptive mycobacterium tuberculosis h37rv strain and two clinically isolated multidrug-resistant strains. compounds 11l and 11m display acceptable sa ... | 2017 | 28626525 |
| miliary tuberculosis in a young woman with hemophagocytic syndrome: a case report and literature review. | we herein report a rare case of miliary tuberculosis-associated hemophagocytic syndrome (hps) complicated with respiratory failure. a 19-year-old japanese woman with a fever, general malaise, and chest radiograph abnormalities was referred to our hospital. after admission, she developed respiratory failure with pancytopenia. a histological examination of lung and bone marrow biopsy samples revealed noncaseating granulomas without evidence of acid-fast bacilli or lymphoma. in addition, a bone mar ... | 2017 | 28626190 |
| bedaquiline: a new hope for shorter and better anti-tuberculosis regimens. | in 2014, an estimated 1.8 million people died from mycobacterium tuberculosis (mtb); moreover, 680,000 people developed multidrug-resistant tb (mdr-tb). | 2017 | 28625141 |
| vitamin d status in under-five children with a history of close tuberculosis contact in padang, west sumatra. | serum vitamin d influences cellular immunity against mycobacterium tuberculosis, particularly in under-five children. vitamin d insufficiency and deficiency as well as tuberculosis (tb) are highly prevalent in indonesia. this study described the association of serum vitamin d in the incidence of latent tb in under-five children with a history of close tb contact. | 2017 | 28625040 |
| lansoprazole-sulfide, pharmacokinetics of this promising anti-tuberculous agent. | lansoprazole (lpz) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (lpzs) was recently reported to have in vitro and in vivo activity against mycobacterium tuberculosis. it was also reported that a 300 mg kg(-1) oral administration of lpzs was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. a validated liquid chromatography-tandem mass spectrometric method (lc-ms/ms) for the simultaneous quantif ... | 2017 | 28623874 |
| identification of mycobacterium species by maldi-tof mass spectrometry. | matrix-assisted laser desorption ionization - time-of-flight (maldi-tof) mass spectrometry enables to identify microorganisms by comparison of the protein content with reference spectra in the database. the aim of this study was to evaluate the efficacy of phenotypic identification of mycobacteria by maldi-tof mass spectrometry in laboratory practice. seventy five isolates of mycobacteria were identified by molecular and phenotypic method, and the results were compared by maldi-tof. for maldi-to ... | 2017 | 28623484 |
| xtractb assay, a mycobacterium tuberculosis molecular screening test with sensitivity approaching culture. | nucleic acid amplification tests are increasingly used to diagnose tuberculosis (tb) due to their speed and sensitivity compared to sputum smear microscopy. however, these tests fail to equal culture's sensitivity with sputum smear microscopy negative specimens and therefore cannot be used to rule out tb disease. for molecular tests to match culture's sensitivity, they must detect ≤10 genomic copies of mycobacterium tuberculosis (mtb) dna, the limit of detection of culture, process ≥1 ml of sput ... | 2017 | 28623303 |
| screening mutations in drug-resistant mycobacterium tuberculosis strains in yunnan, china. | drug-resistant tuberculosis (dr-tb), especially multidrug-resistant tuberculosis (mdr-tb), is a serious medical and societal problem in china. the purpose of this study was to evaluate the mutation characteristics of drug-resistant mycobacterium tuberculosis (m. tuberculosis) isolates in yunnan, china. drug susceptibility testing (dst) was performed in 523 clinical m. tuberculosis isolates. six drug resistance genes (katg, inha, rpob, rpsl, embb, and pnca) were selected to screen for mutations. ... | 2017 | 28623123 |
| antimycobacterial metabolism: illuminating mycobacterium tuberculosis biology and drug discovery. | bacteria are capable of performing a number of biotransformations that may activate or deactivate xenobiotics. recent efforts have utilized metabolomics techniques to study the fate of small-molecule antibacterials within the targeted organism. examples involving mycobacterium tuberculosis are reviewed and analyzed with regard to the insights they provide as to both activation and deactivation of the antibacterial. the studies, in particular, shed light on biosynthetic transformations performed ... | 2017 | 28622844 |
| discovery of indeno[1,2-c]quinoline derivatives as potent dual antituberculosis and anti-inflammatory agents. | a series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-tb) and anti-inflammatory activities. the minimum inhibitory concentration (mic) of the newly synthesized compound was tested against mycobacterium tuberculosis h37rv. among the tested compounds, (e)-n'-[6-(4-hydroxypiperidin-1-yl)-11h-indeno[1,2-c]quinolin-11-ylidene]isonicotino-hydrazide (12), exhibited significant activities against the growth of m. tuberculosis (mic value ... | 2017 | 28621733 |
| comparison of the characteristics of mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients. | mycobacterium tuberculosis (mtb) in sputum originates from lung cavities in tuberculosis (tb) patients. but drug susceptibility testing (dst) of sputum mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. this could be one of the reasons for low cure rates for multi-drug resistant (mdr)-tb. we studied ... | 2017 | 28620844 |
| vitamin d counteracts mycobacterium tuberculosis-induced cathelicidin downregulation in dendritic cells and allows th1 differentiation and ifnγ secretion. | tuberculosis (tb) presents a serious health problem with approximately one-third of the world's population infected with mycobacterium tuberculosis in a latent state. experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin d in patients with tb. at the same time, experimental data have shown that th1 cells through production of ifnγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of ... | 2017 | 28620394 |
| the antibacterial prodrug activator rv2466c is a mycothiol-dependent reductase in the oxidative stress response of mycobacterium tuberculosis. | the mycobacterium tuberculosis rv2466c gene encodes an oxidoreductase enzyme annotated as dsba. it has a cpwc active-site motif embedded within its thioredoxin fold domain and mediates the activation of the prodrug tp053, a thienopyrimidine derivative that kills both replicating and nonreplicating bacilli. however, its mode of action and actual enzymatic function in m. tuberculosis have remained enigmatic. in this study, we report that rv2466c is essential for bacterial survival under h2o2 stres ... | 2017 | 28620052 |
| complete genome sequence of a mycobacterium tuberculosis strain belonging to the east african-indian family in the indo-oceanic lineage, isolated in hanoi, vietnam. | the east african-indian (eai) family of mycobacterium tuberculosis is an endemic group mainly observed in southeast asia. here, we report the complete genome sequence of an m. tuberculosis strain isolated as a member of the eai family in hanoi, vietnam, a country with a high incidence of tuberculosis. | 2017 | 28619797 |
| systemic immunological changes in patients with distinct clinical outcomes during mycobacterium tuberculosis infection. | the lung lesions in an individual infected with tuberculosis (tb) are surprisingly variable and independent of each other. however, there is no circulating biomarker yet able to segregate patients according to the extent of lung lesions. | 2017 | 28619539 |
| antigen availability shapes t cell differentiation and function during tuberculosis. | cd4 t cells are critical for protective immunity against mycobacterium tuberculosis (mtb), the cause of tuberculosis (tb). yet to date, tb vaccine candidates that boost antigen-specific cd4 t cells have conferred little or no protection. here we examined cd4 t cell responses to two leading tb vaccine antigens, esat-6 and ag85b, in mtb-infected mice and in vaccinated humans with and without underlying mtb infection. in both species, mtb infection drove esat-6-specific t cells to be more different ... | 2017 | 28618268 |
| decreased expression of perforin in cd8(+) t lymphocytes in patients with mycobacterium tuberculosis infection and its potential value as a marker for efficacy of treatment. | cytolytic activity against mycobacteria tuberculosis (mtb) within the infected macrophage is a crucial step in the immunity against tb infection, as mtb is an intracellular bacterium. cytotoxic molecules such as perforin and granzymes produced by cytolytic t cells directly participate in this process. in this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (ifn-γ), perforin and granzyme b in cd8(+) t cells from patients w ... | 2017 | 28616288 |