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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.201728619539
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.201728619797
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 ...201728620052
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 ...201728620394
immunogenicity and protective efficacy of a fusion protein tuberculosis vaccine combining five esx family proteins.one strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on t cell antigens. in this study, we have evaluated the vaccine potential of a fusion protein combining esxb, esxd, esxg, esxu, and esxm of mycobacterium tuberculosis (m. tb). this recombinant protein, named bm, was expressed in and purified from escherichia coli. immunization of c57bl/6 mice with purified bm protein formulated in freund's incomplete adjuvant induced the production of th1 ...201728620588
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 ...201728620844
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 ...201728621733
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 ...201728622844
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. ...201728623123
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 ...201728623303
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 ...201728623484
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 ...201728623874
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.201728625040
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).201728625141
immunogenicity and therapeutic effects of recombinant ag85ab fusion protein vaccines in mice infected with mycobacterium tuberculosis.the immune function of tuberculosis (tb) patients is disordered. by using immune regulators to assist chemotherapy for tb the curative effect might be improved. in this study, a vaccine containing mycobacterium tuberculosis (m. tuberculosis) recombinant ag85ab fusion protein (rag85ab) was constructed and evaluated. the mice were immunized intramuscularly three times at two-week intervals with ag85ab fusion protein combined with corynebacterium parvum adjuvant (rag85ab+cp). in comparison to contr ...201728625522
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 ...201728626190
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 ...201728626525
prevalence of multidrug-resistant tuberculosis cases among hiv-positive and hiv-negative patients eligible for retreatment regimen in togo using genexpert mtb/rif.drug-resistant tuberculosis (tb) is emerging as an important health problem in togo. from sputum of previously treated tb patients, multidrug-resistant (mdr) tb was diagnosed in 24% (10/42) patients via genexpert mtb/rif compared to 25% (6/24) patients via conventional drug susceptibility testing (bactec mgit 960 system). the agreement between these two methods to detect mdr-tb is excellent. however, genexpert mtb/rif offers the advantage of rapidly detecting mycobacterium tuberculosis complex i ...201528626586
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 ...201728627431
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.201728627432
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 ...201728627635
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 ...201728627673
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 ...201728627738
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 ...201728628665
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 ...201728628823
β-ca-specific inhibitor dithiocarbamate fc14-584b: a novel antimycobacterial agent with potential to treat drug-resistant tuberculosis.inhibition of novel biological pathways in mycobacterium tuberculosis (mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. in vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-ca) inhibitors fc14-594 a and fc14-584b effectively inhibit the activity of mtb β-ca enzymes. we screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on m. marinum in a zebrafish model. in o ...201728629306
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.201728629614
listeria-vectored vaccine expressing the mycobacterium tuberculosis 30 kda major secretory protein via the constitutively active prfa* regulon boosts bcg efficacy against tuberculosis.a potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective bcg vaccine. here we investigate novel live attenuated recombinant listeria monocytogenes (rlm) vaccines expressing the mycobacterium tuberculosis (mtb) 30 kda major secretory protein (r30/ag85b) (rlm30) as heterologous booster vaccines in animals primed with bcg. using three attenuated lm vectors, rlm ...201728630063
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. ...201728630193
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 ...201728630203
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 ...201728630205
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 ...201728630430
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 ...201728631643
evaluation of a new rapid kit, bd mgit tbc identification test for confirmation of mycobacterium tuberculosis complex.at present, three rapid kits are available globally for the confirmation of mycobacterium tuberculosis complex (mtbc) in cultures by mpt64 antigen (mpt64 ag) detection. these include capilia tb, sd bioline, and bd mgit tbc identification (tbcid). the third kit is yet to be validated in india. we have tested this kit and compared with sd bioline using conventional tests as gold standard. seventy-one mtbc (70 m. tuberculosis and one mycobacterium bovis) and four nontuberculous mycobacteria (ntm) w ...201728631644
evaluation of the genotype mtbdrsl test for detection of second-line drug resistance in drug-resistant mycobacterium tuberculosis strains in myanmar. 201728631943
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 ...201728632406
taking control: hijacking of rab gtpases by intracellular bacterial pathogens.intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. to establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. since rab-family gtpases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack rab gtpases dynamics and trafficking functions. one such strategy i ...201728632996
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.201728633546
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 ...201728633695
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.201728633705
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 ...201728634299
whole blood profiling of bacillus calmette-guérin-induced trained innate immunity in infants identifies epidermal growth factor, il-6, platelet-derived growth factor-ab/bb, and natural killer cell activation.vaccination of infants with bacillus calmette-guérin (bcg) activates both the innate and adaptive arms of the immune response. the antimycobacterial effects of these responses most likely account for the ability of bcg to protect against childhood forms of tuberculosis (tb). there is also evidence for a heterologous protective effect of bcg vaccination against tb-unrelated mortality in low birth weight infants. a possible mechanism of action of this effect, the induction of trained innate immuni ...201728634479
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 ...201728635627
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. ...201728636311
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 ...201728636589
microrna-144-3p inhibits autophagy activation and enhances bacillus calmette-guérin infection by targeting atg4a in raw264.7 macrophage cells.micrornas (mirnas) are small noncoding nucleotides that play major roles in the response of host immune cells. autophagy plays a key role in activating the antimicrobial host defense against mycobacterium tuberculosis (m. tuberculosis). whether mirnas specifically influence the activation of macrophage autophagy during m. tuberculosis infection is largely unknown. in the present study, we demonstrate that mycobacterium bovis bacillus calmette-guérin (bcg) infection of macrophages leads to increa ...201728636635
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.201728639565
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 ...201728642013
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 ...201728642632
the impact of genome region of difference 4 (rd4) on mycobacterial virulence and bcg efficacy.comparative genome analyses have revealed a number of regions of difference (rd) among mycobacterial species. the functional consequences of most of these genome variations have not been studied. rd4, which encompasses rv1506c-rv1516c of mycobacterium tuberculosis (m. tb) h37rv, is absent in the closely related mycobacterium bovis and m. bovis bacille calmette-guérin (bcg). on the other hand, we previously found that mycobacterium marinum has an extended rd4 which includes a number of genes invo ...201728642843
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 ...201728642844
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 ...201728642848
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 ...201728646039
anti-tuberculosis bacteriophage d29 delivery with a vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler.to compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) d29 with three inhalation devices.201728646325
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 ...201728646367
hydroxylamine-induced oxidation of ferrous carbonylated truncated hemoglobins from mycobacterium tuberculosis and campylobacter jejuni is limited by carbon monoxide dissociation.hydroxylamine (ha) is an oxidant of ferrous globins and its action has been reported to be inhibited by co, even though this mechanism has not been clarified. here, kinetics of the ha-mediated oxidation of ferrous carbonylated mycobacterium tuberculosis truncated hemoglobin n and o (mt-trhbn(ii)-co and mt-trhbo(ii)-co, respectively) and campylobacter jejuni truncated hemoglobin p (cj-trhbp(ii)-co), at ph 7.2 and 20.0 °c, are reported. mixing mt-trhbn(ii)-co, mt-trhbo(ii)-co, and cj-trhbp(ii)-co ...201728646425
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 ...201728646952
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 ...201728647504
[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 ...201728647985
detection of mycobacteria by culture and dna-based methods in animal-derived food products purchased at spanish supermarkets.mycobacteria include obligate and opportunistic pathogens that cause significant human and animal disease. the burden of tuberculosis has been largely reduced in developed territories but remains a huge problem worldwide. the significance of nontuberculous mycobacteria is growing considerably, especially in developed regions with higher life expectancy and more therapy-related immunosuppressed individuals. due to their robustness mycobacteria can contaminate animal products by direct transmissio ...201728649235
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 ...201728650996
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 ...201728651002
[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 ...201728651408
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.201728652186
nifurtimox is ineffective against drug-resistant mycobacteria. 201728652235
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 ...201728652330
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.201728652786
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 ...201728654200
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 ...201728655597
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 ...201728655852
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 ...201728657202
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 ...201728657321
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 ...201728657441
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 ...201728658275
development of a one-step multiplex pcr assay for differential detection of major mycobacterium species.the prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (ntm) infection has also emerged worldwide. moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. here, we developed a one-step multiplex pcr assay using whole-genome analysis and bioinformatics to identify novel molecular targets. the aims of this assay were to (i) discriminate between the mycobacterium tuberculosis complex (mtbc) and n ...201728659320
an alert of mycobacterium tuberculosis infection of rhesus macaques in a wild zoo in china.mycobacterium tuberculosis, the pathogen that causes tuberculosis (tb), is becoming increasingly recognized as an important cause of fatal chronic illnesses in china. in this study, we report an infectious disease among 84 rhesus macaques at a chinese zoo. their clinical signs and symptoms were very similar with the manifestations of tb in humans. to determine the potential pathogens of this outbreak, many methods were used. first, tuberculin skin tests showed that none of the monkeys displayed ...201728659540
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 ...201728659881
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 ...201728660225
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 ...201728660459
glycosylation of recombinant antigenic proteins from mycobacterium tuberculosis: in silico prediction of protein epitopes and ex vivo biological evaluation of new semi-synthetic glycoconjugates.tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (lam), with antigenic proteins from mycobacterium tuberculosis (mtb), has been proposed as a new strategy for developing efficient vaccines. in this work, we investigated the effect of the chemical glycosylation on two recombinant mtb proteins produced in e. coli with an additional seven-amino acid tag (re ...201728661444
cutaneous mycobacterium haemophilum infections in immunocompromised patients in a tertiary hospital in bangkok, thailand: under-reported/under-recognized infection.mycobacterium haemophilum is one of the non-tuberculous mycobacteria (ntm) that can cause cutaneous infection. as acid-fast staining cannot distinguish ntm from mycobacterium tuberculosis, and as skin culture for m. haemophilum is not performed routinely, the diagnosis of m. haemophilum infection in thailand is rarely made.201428663805
recovery rates of non-tuberculous mycobacteria from clinical specimens are increasing in korean tertiary-care hospitals.non-tuberculous mycobacteria (ntm) are being recognized increasingly as the causative agents of opportunistic infections in humans. this study investigated the epidemiologic trends of ntm recovery from various clinical specimens in 2 korean tertiary-care hospitals. we reviewed the laboratory records of patient samples cultured for mycobacteria between 2009 and 2015 at 2 tertiary-care hospitals in korea. the medical records for patients with positive ntm samples were also reviewed. during the stu ...201728665061
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 ...201728665555
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 ...201728665588
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.201728665743
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 ...201728665948
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 ...201728666374
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 ...201728667013
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 ...201728668684
salicylaldehyde and dihydroisobenzofuran derivatives from the marine fungus zopfiella marina.two salicylaldehyde derivatives (1 and 2), a hydroxymethylphenol (3), five dihydroisobenzofuran (4-8) derivatives, and a 5-chloro-3-deoxyisoochracinic acid (9), together with a known 3-deoxyisoochracinic acid (10) were isolated from the marine fungus zopfiella marina bcc 18240 (or nbrc 30420). the structures of these compounds were elucidated by extensive spectroscopic analysis. compound 1 showed weak antituberculous activity against mycobacterium tuberculosis h37ra, and antibacterial activity a ...201728669223
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 ...201728669536
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 ...201728669673
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. ...201728669977
epidemiology of musculoskeletal tuberculosis in an area with high disease prevalence.retrospective observational study.201728670408
evaluation of the mycobacterium tuberculosis so2 vaccine using a natural tuberculosis infection model in goats.the development of new vaccines against animal tuberculosis (tb) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. in this study, the protection conferred by the mycobacterium tuberculosis so2 experimental vaccine was evaluated using a natural infection model in goats. twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously ...201728671074
mycobacterium tuberculosis hypoxic response protein 1 (hrp1) augments the pro-inflammatory response and enhances the survival of mycobacterium smegmatis in murine macrophages.the dosr/doss two-component regulatory system of mycobacterium tuberculosis regulates the expression of numerous genes under stress conditions and is important for the long-term survival of m. tuberculosis in the host. the rv2626c gene of m. tuberculosis is one of the most strongly induced transcripts of the dormancy regulon. this study focused on the immunological effects and possible function of rv2626c in maintaining mycobacterial survival under various stress conditions.201728671529
a small-molecule allosteric inhibitor of mycobacterium tuberculosis tryptophan synthase.new antibiotics with novel targets are greatly needed. bacteria have numerous essential functions, but only a small fraction of such processes-primarily those involved in macromolecular synthesis-are inhibited by current drugs. targeting metabolic enzymes has been the focus of recent interest, but effective inhibitors have been difficult to identify. we describe a synthetic azetidine derivative, brd4592, that kills mycobacterium tuberculosis (mtb) through allosteric inhibition of tryptophan synt ...201728671682
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 ...201728672070
rare presentation of intractable tuberculous panophthalmitis with intraocular and intraorbital abscesses: a case report.we report a rare presentation of extrapulmonary tuberculosis.201728673337
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.201728674058
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