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mycobacterium tuberculosis atsg (rv0296c), glmu (rv1018c) and sahh (rv3248c) proteins function as the human il-8-binding effectors and contribute to pathogen entry into human neutrophils.mycobacterium tuberculosis is an extremely successful intracellular pathogen that has evolved a broad spectrum of pathogenic mechanisms that enable its manipulation of host defense elements and its survival in the hostile environment inside phagocytes. cellular influx into the site of mycobacterial entry is mediated by a variety of chemokines, including interleukin-8 (il-8), and the innate cytokine network is critical for the development of an adaptive immune response and infection control. usin ...201626829648
classtr: classifying within-host heterogeneity based on tandem repeats with application to mycobacterium tuberculosis infections.genomic tools have revealed genetically diverse pathogens within some hosts. within-host pathogen diversity, which we refer to as "complex infection", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). estimates of the frequency of within-host mutation and reinfection in populations are c ...201626829497
delamanid and bedaquiline resistance in mycobacterium tuberculosis ancestral beijing genotype causing extensively drug-resistant tuberculosis in a tibetan refugee. 201626829425
lysine ε-aminotransferases: kinetic constants, substrate specificities, and the variation in active site residues.l-lysine ε-aminotransferase (lysat) is an important enzyme in tailoring the terminal amino group of l-lysine or l-ornithine and can be directed to the synthesis of various value-added chemicals such as adipic acid. three lysats, lysat from saccharopolyspora erythraea nrrl 2338 (lysat_sery), lysat from nocardia farcinica ifm 10152, and lysat from rhodococcus jostii rha1, were cloned, and their kinetic values and substrate specificities were investigated. in the reaction using 5mm l-lysine and 10m ...201626827769
a large cohort study on the clinical value of simultaneous amplification and testing for the diagnosis of pulmonary tuberculosis.the ampsure simultaneous amplification and testing method for the detection of mycobacterium tuberculosis (sat-tb assay) was designed to diagnose rapidly pulmonary tuberculosis (ptb). unfortunately, the diagnostic advantage is unclear from previous small sample studies. in the current inquiry, a large sample size was used to reevaluate the clinical accuracy of the sat-tb assay using sputum specimens. a total of 3608 patients with suspected ptb were enrolled prospectively for diagnosis from sputu ...201626825909
predominance of modern mycobacterium tuberculosis strains and active transmission of beijing sublineage in jayapura, indonesia papua.mycobacterium tuberculosis genotype distribution is different between west and central indonesia, but there are no data on the most eastern part, papua. we aimed to identify the predominant genotypes of m. tuberculosis responsible for tuberculosis in coastal papua, their transmission, and the association with patient characteristics. a total of 199 m. tuberculosis isolates were collected. spoligotyping was applied to describe the population structure of m. tuberculosis, lineage identification wa ...201626825253
pdxh proteins of mycobacteria are typical members of the classical pyridoxine/pyridoxamine 5'-phosphate oxidase family.pyridoxal 5'-phosphate (plp) biosynthesis is essential for the survival and virulence of mycobacterium tuberculosis (mtb). plp functions as a cofactor for 58 putative plp-binding proteins encoded by the mtb genome and could also act as a potential antioxidant. de novo biosynthesis of plp in mtb takes place through the 'deoxyxylulose 5'-phosphate (dxp)-independent' pathway, whereas pdxh enzymes, possessing pyridoxine/pyridoxamine 5'-phosphate oxidase (pnpox) activity, are involved in the plp salv ...201626823273
multifocal musculoskeletal tuberculosis mimicking multiple bone metastases: a case report.the occurrence of non-contiguous, multiple, and remote involvement tuberculous spondylitis is rare. the clinical presentation in patients with multifocal musculoskeletal tuberculosis may closely mimic that in patients with multiple bone metastases, which makes the accurate clinical diagnosis challenging. herein, we report a multifocal musculoskeletal tuberculosis case that was misdiagnosed for 8 months as multiple bone metastases.201626823075
towards understanding the biological function of the unusual chaperonin cpn60.1 (groel1) of mycobacterium tuberculosis.the 60 kda heat shock proteins, also known as cpn60s (groels) are components of the essential protein folding machinery of the cell, but are also dominant antigens in many infectious diseases. although generally essential for cellular survival, in some organisms such as mycobacterium tuberculosis, one or more paralogous cpn60s are known to be dispensable. in m. tuberculosis, cpn60.2 (groel2) is essential for cell survival, but the biological role of the non-essential cpn60.1 (groel1) is still el ...201626822628
discovery of potent anti-tuberculosis agents targeting leucyl-trna synthetase.tuberculosis is a serious infectious disease caused by human pathogen bacteria mycobacterium tuberculosis. bacterial drug resistance is a very significant medical problem nowadays and development of novel antibiotics with different mechanisms of action is an important goal of modern medical science. leucyl-trna synthetase (leurs) has been recently clinically validated as antimicrobial target. here we report the discovery of small-molecule inhibitors of m. tuberculosis leurs. using receptor-based ...201626822568
the β2 clamp in the mycobacterium tuberculosis dna polymerase iii αβ2ε replicase promotes polymerization and reduces exonuclease activity.dna polymerase iii (dna pol iii) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in mycobacterium tuberculosis (mtb) requires further investigation. we have reconstituted the leading-strand replication process of the mtb dna pol iii holoenzyme in vitro, and investigated the physical and functional relationships between its key components. we verify the presence of an αβ2ε polymerase-clamp-exonuclease replic ...201626822057
draft genome sequence of mycobacterium tuberculosis kt-0192, isolated in south korea.we report the draft genome sequence of totally drug-resistant (xdr) mycobacterium tuberculosis kt-0192. this sequence will provide new insights into the main cause and evolution of drug resistance in m. tuberculosis kt-0192.201626798104
the source of mycobacterium tuberculosis-specific ifn-γ production in peripheral blood mononuclear cells of tb patients.mycobacterium tuberculosis (mtb)-specific ifn-γ secretion plays important roles in anti-tuberculosis (tb) immunity. mtb-specific ifn-γ response can be induced in hiv/tb co-infected patients with a low cd4 lymphocyte count; this suggests that the source of mtb-specific ifn-γ production is not limited in cd4(+) t lymphocytes. currently, the major sources of mtb-specific ifn-γ production and the function and phenotype of mtb-specific ifn-γ-producing cells still remain unclear. thirty-nine participa ...201626796515
[drug-resistant tuberculosis. epidemiology, diagnostics and therapy].drug-resistant tuberculosis (dr-tb) is one of the serious problems in the fight against tuberculosis on a global scale. this review article describes in brief the global epidemiology, diagnostics and treatment of dr-tb. the situation in germany, switzerland and austria is addressed in detail. the article concludes with a presentation of current research topics in the field of resistant tb.201626795948
a strip array for spoligotyping of mycobacterium tuberculosis complex isolates.a novel strip array was developed for a nine-spacer spoligotyping scheme of mycobacterium tuberculosis complex (mtbc). the new method was evaluated using 211 mtbc isolates and the results were fully concordant with the traditional spoligotyping approach. the strip array proved to be rapid and convenient for spoligotyping of mtbc.201626795021
tuberculosis in newborns: the lessons of the "lübeck disaster" (1929-1933).in an accident later known as the lübeck disaster, 251 neonates were orally given three doses of the new bacille calmette-guérin (bcg) antituberculosis (tb) vaccine contaminated with mycobacterium tuberculosis. a total of 173 infants developed clinical or radiological signs of tb but survived the infection, while 72 died from tb. while some blamed the accident on bcg itself by postulating reversion to full virulence, such a possibility was conclusively disproven. rather, by combining clinical, m ...201626794678
wheeling and dealing with antigen presentation in tuberculosis.in tuberculosis, antigens are transferred from infected to uninfected dendritic cells. does this favor t lymphocyte response and anti-mycobacterial host defense? in a recent report published in cell host & microbe, ernst and colleagues show that mycobacterium tuberculosis seems to have hijacked this mechanism for its own benefit.201626794467
mycobacterium tuberculosis can gain access to adipose depots of mice infected via the intra-nasal route and to lungs of mice with an infected subcutaneous fat implant.mycobacterium tuberculosis (mtb), the causative agent of tuberculosis has the remarkable ability to persist as non-replicating forms in the host. these persisters are tolerant to drugs targeting actively replicating bacilli and hence are responsible for the need of an extended duration of anti-tubercular therapy. the anatomical locations and cell types housing mtb persisters are being investigated in the recent times. adipose tissue and the adipocytes are proposed niches of mtb persisters. in th ...201626792675
recombinant bcg prime and ppe protein boost provides potent protection against acute mycobacterium tuberculosis infection in mice.since bcg, the only vaccine widely used against tuberculosis (tb) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against tb. prime-boost is proven to be a good strategy by inducing long-term protection. in this study, we tested the protective effect against mycobacterium tuberculosis (mtb) challenge of prime-boost strategy by recombina ...201626792673
the drug binding sites and transport mechanism of the rnd pumps from mycobacterium tuberculosis: insights from molecular dynamics simulations.rnd permease superfamily drug efflux pumps are involved in multidrug transport and are attractive to study them for therapeutic purpose. in previous work we have classified 14 members of mmpl proteins belong to rnd superfamily from mycobacterium tuberculosis (mtb) within its families [sandhu p. and akhter y., 2015. int. j. med. microbiol., 305:413-423]. in this study, structures of these proteins are homology modelled. the drug binding sites and channels are identified using local micro-stereoch ...201626792538
fluoroquinolone interactions with mycobacterium tuberculosis gyrase: enhancing drug activity against wild-type and resistant gyrase.mycobacterium tuberculosis is a significant source of global morbidity and mortality. moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. to guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against m. tuberculosis gyrase and how mutations in the enzyme cause resistance. therefore, we characterized interactions of fluoroquinolones and relat ...201626792518
redefining mtbdrplus test results: what do indeterminate results actually mean?although line-probe assays (lpas) are promising, little research has been conducted to elucidate the true nature of indeterminate lpa results or assess the ability of these assays to perform on a wide range of clinical samples.201626792465
mycobacterial diversity causing multi- and extensively drug-resistant tuberculosis in djibouti, horn of africa.on detecting a high prevalence of multidrug-resistant tuberculosis (tb) in djibouti, 32 mycobacterium tuberculosis isolates of patients hospitalised in the tb referral centre of the capital were genotyped. a high variety of m. tuberculosis lineages, including lineage 1, indo-oceanic, lineage 2, east-asian, lineage 3, east-african indian and lineage 4, euro-american, were detected.201626792464
a whole genome bioinformatic approach to determine potential latent phase specific targets in mycobacterium tuberculosis.current tuberculosis treatment is long and expensive, faces the increasing burden of mdr/xdr strains and lack of effective treatment against latent form, resulting in an urgent need of new anti-tb drugs. key to tb biology is its capacity to fight the host's rnos mediated attack. rnos are known to display a concentration dependent mycobactericidal activity, which leads to the following hypothesis "if we know which proteins are targeted by rnos and kill tb, we we might be able to inhibit them with ...201626791267
new targets and cofactors for the transcription factor lrpa from mycobacterium tuberculosis.rv3291c (mtblrpa), a transcriptional regulator, belongs to the leucine-responsive regulatory protein (lrp) family and is thought to play an important role in mycobacterium tuberculosis persistence. in this study, we verified 17 novel potential binding sites for mtblrpa by in vitro binding assays on the basis of previous predictions from an in silico analysis and bacterial one-hybrid (bih) reporter system. amino acids, such as tyrosine, phenylalanine, tryptophan, and histidine, strongly affect th ...201626789099
a simple and rapid method for measuring α-d-phosphohexomutases activity by using anion-exchange chromatography coupled with an electrochemical detector.the interconversion of hexose-6-phosphate and hexose-1-phosphate can be directly analyzed by high-performance anion-exchange chromatography coupled with an electrochemical detector (hpaec-pad). thus, this method can be used to measure the activities of n-acetylglucosamine-phosphate mutase (agm), glucosamine-phosphate mutase (glmm) and phosphoglucomutase (pgm), which are the members of α-d-phosphohexomutases superfamily. the detection limits were extremely low as 2.747 pmol, 1.365 pmol, 0.512 pmo ...201626788420
gene expression profiling identifies candidate biomarkers for active and latent tuberculosis.tuberculosis (tb) is a serious infectious disease in that 90% of those latently infected with mycobacterium tuberculosis present no symptoms, but possess a 10% lifetime chance of developing active tb. to prevent the spread of the disease, early diagnosis is crucial. however, current methods of detection require improvement in sensitivity, efficiency or specificity. in the present study, we conducted a microarray experiment, comparing the gene expression profiles in the peripheral blood mononucle ...201626818387
[macrophage activation syndrome revealing disseminated mycobacterium tuberculosis]. 201626815530
the defect in autophagy induction by clinical isolates of mycobacterium tuberculosis is correlated with poor tuberculosis outcomes.tuberculosis (tb) represents a major global health problem. the prognosis of clinically active tuberculosis depends on the complex interactions between mycobacterium tuberculosis (mtb) and its host. in recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including mtb. in present study, we aim to investigate the relationship of autophagy induction by clinical isolates of mtb with the clinical outcomes in patients with tb.201626815035
computationally guided identification of novel mycobacterium tuberculosis glmu inhibitory leads, their optimization, and in vitro validation.mycobacterium tuberculosis (mtb) infections are causing serious health concerns worldwide. antituberculosis drug resistance threatens the current therapies and causes further need to develop effective antituberculosis therapy. glmu represents an interesting target for developing novel mtb drug candidates. it is a bifunctional acetyltransferase/uridyltransferase enzyme that catalyzes the biosynthesis of udp-n-acetyl-glucosamine (udp-glcnac) from glucosamine-1-phosphate (glcn-1-p). udp-glcnac is a ...201626812086
a review of clinical models for the evaluation of human tb vaccines.while much progress has been made in the fight against the scourge of tuberculosis (tb), we are still some way from reaching the ambitious targets of eliminating it as a global public health problem by the mid twenty-first century. a new and effective vaccine that protects against pulmonary tb disease will be an essential element of any control strategy. over a dozen vaccines are currently in development, but recent efficacy trial data from one of the most advanced candidates have been disappoin ...201626810964
mycobacterium tuberculosis mutations associated with reduced susceptibility to linezolid.linezolid (lzd) has become increasingly important for the treatment of multidrug-resistant tuberculosis (mdr-tb), but its mechanisms of resistance are not well characterized. we isolated 32 mutants ofmycobacterium tuberculosiswith reduced susceptibility to lzd, which was accounted for byrrlandrplcmutations in almost equal proportions, causing lower and higher mics, respectively. our findings provide useful information for the rapid detection of lzd resistance for improved treatment of mdr-tb.201626810645
pattern of drug resistance and risk factors associated with development of drug resistant mycobacterium tuberculosis in pakistan.drug resistant tuberculosis (dr-tb) is a major public health problem in developing countries such as pakistan.201626809127
in vitro evaluation of inhalable verapamil-rifapentine particles for tuberculosis therapy.recent studies have demonstrated that efflux pumps of mycobacterium tuberculosis (m. tb) provide a crucial mechanism in the development of drug resistant to antimycobacterial drugs. drugs that inhibit these efflux pumps, such as verapamil, have shown the potential in enhancing the treatment success. we therefore hypothesized that the combined inhaled administration of verapamil and a first-line rifamycin antibiotic will further improve the treatment efficacy. an inhalable dry powder consisting o ...201626808409
characteristics of patients with smear-negative pulmonary tuberculosis (tb) in a region with high tb and hiv prevalence.smear-negative pulmonary tb (snpt) represents 30-60% of all pulmonary tb cases. the mortality of these patients can reach 25% in populations with high prevalence of hiv infection, and 10-20% of tb transmission at the population level are attributable to snpt cases.201626808299
real-time investigation of tuberculosis transmission: developing the respiratory aerosol sampling chamber (rasc).knowledge of the airborne nature of respiratory disease transmission owes much to the pioneering experiments of wells and riley over half a century ago. however, the mechanical, physiological, and immunopathological processes which drive the production of infectious aerosols by a diseased host remain poorly understood. similarly, very little is known about the specific physiological, metabolic and morphological adaptations which enable pathogens such as mycobacterium tuberculosis (mtb) to exit t ...201626807816
direct detection of mycobacterium tuberculosis in sputum: a validation study using solid phase extraction-gas chromatography-mass spectrometry.tuberculosis (tb) remains a worldwide health problem, especially in developing countries. correct identification of mycobacterium tuberculosis (mtb) infection is extremely important for providing appropriate treatment and care to patients. here we describe a solid phase extraction-gas chromatography-mass spectrometry method (spe-thm-gc-ms) for the detection of five biomarkers for m. tuberculosis. the method for classification is developed and validated through the analysis of 112 sputum samples ...201626807702
a fragment merging approach towards the development of small molecule inhibitors of mycobacterium tuberculosis ethr for use as ethionamide boosters.with the ever-increasing instances of resistance to frontline tb drugs there is the need to develop novel strategies to fight the worldwide tb epidemic. boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial transcriptional repressor protein ethr is an attractive therapeutic strategy. herein we report the use of a fragment based drug discovery approach for the structure-guided systematic merging of two fragment molecules, each binding twice to the ...201626806381
genotypic characterization of multi-drug-resistant mycobacterium tuberculosis isolates in myanmar.the number of multi-drug-resistant tuberculosis (mdr-tb) cases is rising worldwide. as a countermeasure against this situation, the implementation of rapid molecular tests to identify mdr-tb would be effective. to develop such tests, information on the frequency and distribution of mutations associating with phenotypic drug resistance in mycobacterium tuberculosis is required in each country. during 2010, the common mutations in the rpob, katg and inha of 178 phenotypically mdr m. tuberculosis i ...201626806152
effects of halide ions on the carbamidocyclophane biosynthesis in nostoc sp. cavn2.in this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium nostoc sp. cavn2 was investigated. in contrast to ki and kf, supplementation of the culture medium with kcl or kbr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. lc-ms analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. in addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 ...201626805858
structure-guided discovery of antitubercular agents that target the gyrase atpase domain.in this study we explored the pharmaceutically underexploited atpase domain of dna gyrase (gyrb) as a potential platform for developing novel agents that target mycobacterium tuberculosis. in this effort a combination of ligand- and structure-based pharmacophore modeling was used to identify structurally diverse small-molecule inhibitors of the mycobacterial gyrb domain based on the crystal structure of the enzyme with a pyrrolamide inhibitor (pdb id: 4bae). pharmacophore modeling and subsequent ...201626805396
synthesis and antimicrobial activity of 4-chloro-3-nitrophenylthiourea derivatives targeting bacterial type ii topoisomerases.a series of novel 4-chloro-3-nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. most of compounds exhibited high antibacterial activity against both standard and hospital strains (mic values 0.5-2 μg/ml), as compared to ciprofloxacin. derivatives with 3,4-dichlorophenyl (11) and 3-chloro-4-methylphenyl (13) substituents were the most promising towards gram-positive pathogens. both of them exhibited antibiofilm poten ...201626804238
association between human leukocyte antigen class ii and pulmonary tuberculosis due to mycobacterium tuberculosis in uganda.mycobacterium tuberculosis (mtb) is reported to infect about a third of the world's population but only 10% are thought to develop active tuberculosis (tb) disease. host immunity regulated by human leukocyte antigens (hla) is an important determinant of the outcome of the disease. here we investigate hla class ii gene polymorphisms in susceptibility to tb, and whether particular hla class ii alleles were associated with tb in uganda.201626803588
[cutaneous mycobacterium tuberculosis infection associated with reactive paniculitis]. 201626803459
the complexity of diagnosing latent tuberculosis infection in older adults in long-term care facilities.in the usa, tuberculosis disease rates are highest in older adults. diagnostic testing for latent tuberculosis infection (ltbi) has not been evaluated carefully in this group. the aim of this study was to define the relationship between tuberculin skin test (tst) results, t-spot.tb results, and t-cell responses to mycobacterium tuberculosis antigens.201626802447
polymorphism of fcgr2a, fcgr2c, and fcgr3b genes in the pathogenesis of sarcoidosis.we have previously presented evidence that the polymorphism of the fcgr3a gene, encoding the receptor for fc fragment of immunoglobulin g iiia (fcγriiia) plays a role in the enhancement of circulating immune complexes (cis) with the occurrence of mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis (sa). the immunocomplexemia might be caused by decreased affinity of cis to fcγ receptors, with the subsequently decreased receptor clearance by immune cells. in the present stu ...201626801149
phosphate starvation: a novel signal that triggers esx-5 secretion in mycobacterium tuberculosis.mycobacterium tuberculosis uses the type vii esx secretion systems to transport proteins across its complex cell wall. esx-5 has been implicated in m. tuberculosis virulence, but the regulatory mechanisms controlling esx-5 secretion were unknown. here we uncover a link between esx-5 and the pst/senx3-regx3 system that controls gene expression in response to phosphate availability. the dna-binding response regulator regx3 is normally activated by phosphate limitation. deletion of psta1, which enc ...201626800324
the α10 helix of devr, the mycobacterium tuberculosis dormancy response regulator, regulates its dna binding and activity.the crystal structures of several bacterial response regulators provide insight into the various interdomain molecular interactions potentially involved in maintaining their 'active' or 'inactive' states. however, the requirement of high concentrations of protein, an optimal ph and ionic strength buffers during crystallization may result in a structure somewhat different from that observed in solution. therefore, functional assessment of the physiological relevance of the crystal structure data ...201626799615
fused mycobacterium tuberculosis multi-stage immunogens with an fc-delivery system as a promising approach for the development of a tuberculosis vaccine.tuberculosis (tb) remains a major health problem worldwide. currently, the bacilli calmette-guérin (bcg) is the only available licensed tb vaccine, which has low efficacy in protection against adult pulmonary tb. therefore, the development of a safe and effective vaccine against tb needs global attention. in the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (cfp-10) and heat shock protein x (hspx) of mycobacterium tuberculosis fused to the fc domai ...201626835592
a mycobacterial perspective on tuberculosis in west africa: significant geographical variation of m. africanum and other m. tuberculosis complex lineages.phylogenetically distinct mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity. consequently, understanding mycobacterial population structures phylogeographically is essential for design, interpretation and generalizability of clinical trials. comprehensive efforts are lacking to date to establish the west african mycobacterial population structure on a sub-continental scale, which has diagnostic implications and can inform the design of clinical tb trials.201626964059
structure and mapping of spontaneous mutational sites of pyrr from mycobacterium tuberculosis.the emergence of resistant mycobacterium tuberculosis (mtb) infection and the dearth of drugs against tuberculosis have made it imperative to identify and validate novel targets and classes of drugs for treatment. the pyrimidine operon regulatory protein (pyrr), a regulator of de novo pyrimidine synthesis, is an essential enzyme and a probable 5-fluorouracil (5-fu) target in mtb, with mutations in pyrr attributable to 5-fu resistance. here we report, for the first time, the co-crystal structure ...201626902118
lymphatic endothelial cells are a replicative niche for mycobacterium tuberculosis.in extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (lecs) are involved in immune function. here, we identified lecs, which line the lymphatic vessels, as a niche for mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. in cultured primary human lecs (hlecs), we determined that m. tuberculosis replicates both in the cytosol and within autophagosomes, but the bac ...201626901813
uncommon secondary metabolites from etlingera pavieana rhizomes.from the rhizomes of etlingera pavieana (pierre ex gagnep.) r.m. sm., four phenylpropens, (e)-3-(4-methoxyphenyl)prop-2-en-1-amine (1), (e)-4-methoxycinamaldehyde (2), (e)-4-methoxycinamic acid (3) and (e)-1-methoxy-4-(3-methoxyprop-1-enyl)benzene (4), together with two other compounds, (e)-((e)-3-(4-methoxyphenyl)allyl)3-(4-hydroxyphenyl)acrylate (5) and 4-methoxybenzoic acid (6) were isolated. this is the first report on the presence of all compounds in etlingera. compounds 1 and 5 have been p ...201626901239
non-monotonic response to monotonic stimulus: regulation of glyoxylate shunt gene-expression dynamics in mycobacterium tuberculosis.understanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology. here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network to a monotonic stimulus. we apply this theorem to analyze the non-monotonic dynamics of the σb-regulated glyoxylate shunt gene expression in mycobacterium tuberculosis cells exposed to hypoxia ...201626900694
the secreted protein rv1860 of mycobacterium tuberculosis stimulates human polyfunctional cd8+ t cells.we previously reported that rv1860 protein from mycobacterium tuberculosis stimulated cd4(+)and cd8(+)t cells secreting gamma interferon (ifn-γ) in healthy purified protein derivative (ppd)-positive individuals and protected guinea pigs immunized with a dna vaccine and a recombinant poxvirus expressing rv1860 from a challenge with virulent m. tuberculosis we now show rv1860-specific polyfunctional t (pft) cell responses in the blood of healthy latently m. tuberculosis-infected individuals domina ...201626843486
transmission of tuberculosis among people living in the border areas of poland, the czech republic, and slovakia.in 2007, poland, the czech republic, and slovakia joined the schengen agreement, abolishing restrictions on people crossing the borders. currently, these areas are places of population movements for economic, family, and touristic reasons. this favors the transmission of infectious diseases, including tuberculosis, and requires enhanced control over the spread of the source of infection in the population of patients living in the border areas.201626842376
crystallographic observation of the movement of the membrane-distal domain of the t7ss core component eccb1 from mycobacterium tuberculosis.the protein eccb1, a core component of the type vii secretion system (t7ss) of mycobacterium tuberculosis, has been identified as an atpase and is essential for the secretion of virulence factors by the esx-1 system. in a previous study, eccb1 structures were determined in two different conformations. here, two new conformations are identified and described. these four conformations present snapshots of the swinging movement of the membrane-distal domain a2. the movement of this domain involves ...201626841765
a molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in colombian isolates of mycobacterium tuberculosis.developing a fast, inexpensive, and specific test that reflects the mutations present in mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (tb) control. the objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (mdr) and extensively drug-resistant tb based on single nucleotide polymorphism (snp) mutations present in therpob, katg, inha,ahpc, and gyra genes from colombian ...201626841047
single nucleotide polymorphisms in il17a and il6 are associated with decreased risk for pulmonary tuberculosis in southern brazilian population.in mycobacterium tuberculosis (mtb) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. several single-nucleotide polymorphisms (snps) in cytokine genes have been associated with tuberculosis (tb) outcome. the aim of this study was to evaluate the association between previously reported snps il2-330 t>g (rs2069762); il4-590 c>t (rs2243250); il6-174 g>c (rs ...201626840977
genetic background affects the expansion of macrophage subsets in the lungs of mycobacterium tuberculosis-infected hosts.m1 macrophages are more effective in the induction of the inflammatory response and clearance of mycobacterium tuberculosis than m2 macrophages. infected c57bl/6 mice generate a stronger cellular immune response compared with balb/c mice. we hypothesized that infected c57bl/6 mice would exhibit a higher frequency and function of m1 macrophages than infected balb/c mice. our findings show a higher ratio of macrophages to m2 macrophages in the lungs of chronically infected c57bl/6 mice compared wi ...201626840507
application of discrete wavelet transform for analysis of genomic sequences of mycobacterium tuberculosis.this paper highlights the potential of discrete wavelet transforms in the analysis and comparison of genomic sequences of mycobacterium tuberculosis (mtb) with different resistance characteristics. graphical representations of wavelet coefficients and statistical estimates of their parameters have been used to determine the extent of similarity between different sequences of mtb without the use of conventional methods such as basic local alignment search tool. based on the calculation of the ene ...201626839757
[immune response to mycobacterium tuberculosis].infections with mycobacterium tuberculosis (mtb) induce complex immune responses involving an orchestrated interplay of innate and adaptive immune mechanisms. why the immune system fails to eradicate the pathogen and at best achieves control of infection in the latent stage, still remains an unsolved mystery even more than 100 years after the discovery of mtb by robert koch. this article provides an overview of the current state of the art in the constantly evolving field of tuberculosis (tb) im ...201626838368
local inflammation, dissemination and coalescence of lesions are key for the progression toward active tuberculosis: the bubble model.the evolution of a tuberculosis (tb) infection toward active disease is driven by a combination of factors mostly related to the host response. the equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of tb lesions. in addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. herein we propose a mathematical model that captu ...201626870005
draft genome sequence of mycobacterium tuberculosis kt-0133, isolated in south korea.here, we present the draft genome sequence of mycobacterium tuberculosis kt-0133, which belongs to the korean-beijing family. this sequence will provide a new perspective on the evolution and accommodation of m. tuberculosis kt-0133 in human hosts.201626868407
antimycobacterial activity of methanolic plant extract of artemisia capillaris containing ursolic acid and hydroquinone against mycobacterium tuberculosis.in order to protect against mycobacterium tuberculosis (mtb) infection, novel drugs and new targets should be screened from the vast source of plants. we investigated the potentiality of the herbal plant of artemisia capillaris extract (ac) against mycobacterium tuberculosis.201626867795
high incidence of tuberculosis in patients treated for hepatitis c chronic infection.brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis c carriers and some epidemiological risk scenarios are coincident for both diseases. we analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis c in reference centers in brazil between 2001 and 2012 and reviewed their medical records. eighteen tuberculosis cases were observed in patients submitted to hepatitis c α-interferon-based the ...201626867472
the transmission of mycobacterium tuberculosis in high burden settings.unacceptable levels of mycobacterium tuberculosis transmission are noted in high burden settings and a renewed focus on reducing person-to-person transmission in these communities is needed. we review recent developments in the understanding of airborne transmission. we outline approaches to measure transmission in populations and trials and describe the wells-riley equation, which is used to estimate transmission risk in indoor spaces. present research priorities include the identification of e ...201626867464
assessment of immunological markers and booster effects of ag85b peptides, ag85b, and bcg in blood of bcg vaccinated children: a preliminary report.in the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (pbmcs) of bacillus calmette-guérin (bcg) vaccinated and unvaccinated children were evaluated after vaccination. further, pbmcs of children with low protective levels were boosted with bcg, ag85b, and ag85b peptides to study their booster effects to increase waning bcg induced immunity.201626866022
a microfluidic electrochemical biosensor based on multiwall carbon nanotube/ferrocene for genomic dna detection of mycobacterium tuberculosis in clinical isolates.herein we present a microfluidic-multiplexed platform that integrates electrochemical sensors based on carbon nanotubes associated with ferrocene as redox marker (carbon nanotube (cnt)/ferrocene) for direct detection of pathogenic viral dna from hepatitis c and genomic dna from mycobacterium tuberculosis in clinical isolates. by operating the fluidic device under high flow (150 μl/min), the formation of a very thin depletion layer at the sensor surface (δs = 230 nm) enhances the capture rate up ...201626865908
evaluation of genoflow dr-mtb array test for detection of rifampin and isoniazid resistance in mycobacterium tuberculosis.the aim of this study was to evaluate the genoflow dr-mtb array test (diagcor bioscience, hong kong) on 70 cultured isolates and 50 sputum specimens. the genoflow array test showed good sensitivity and specificity compared to the phenotypic bactec 460tb. this array accurately detected mutations inrpob,katg, andinhaassociated with resistance to rifampin and isoniazid.201626865688
α-glucan biosynthesis and the glge pathway in mycobacterium tuberculosis.it has long been reported that mycobacterium tuberculosis is capable of synthesizing the α-glucan glycogen. however, what makes this bacterium stand out is that it coats itself in a capsule that mainly consists of a glycogen-like α-glucan. this polymer helps the pathogen evade immune responses. in 2010, the biosynthesis of α-glucans has been shown to not only involve the classical enzymes of glycogen metabolism but also a distinct glge pathway. since then, this pathway has attracted attention no ...201626862190
elongation of the poly-γ-glutamate tail of f420 requires both domains of the f420:γ-glutamyl ligase (fbib) of mycobacterium tuberculosis.cofactor f420is an electron carrier with a major role in the oxidoreductive reactions ofmycobacterium tuberculosis, the causative agent of tuberculosis. a γ-glutamyl ligase catalyzes the final steps of the f420biosynthesis pathway by successive additions ofl-glutamate residues to f420-0, producing a poly-γ-glutamate tail. the enzyme responsible for this reaction in archaea (cofe) comprises a single domain and produces f420-2 as the major species. the homologousm. tuberculosisenzyme, fbib, is a t ...201626861878
comparison of indoor contact time data in zambia and western cape, south africa suggests targeting of interventions to reduce mycobacterium tuberculosis transmission should be informed by local data.in high incidence settings, the majority of mycobacterium tuberculosis (m.tb) transmission occurs outside the household. little is known about where people's indoor contacts occur outside the household, and how this differs between different settings. we estimate the number of contact hours that occur between adults and adult/youths and children in different building types in urban areas in western cape, south africa, and zambia.201626861444
disinfectant-susceptibility of multi-drug-resistant mycobacterium tuberculosis isolated in japan.multi-drug-resistant mycobacterium tuberculosis has been an important problem in public health around the world. however, limited information about disinfectant-susceptibility of multi-drug-resistant strain of m. tuberculosis was available.201626858829
central role of pyruvate kinase in carbon co-catabolism of mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) displays a high degree of metabolic plasticity to adapt to challenging host environments. genetic evidence suggests thatmtbrelies mainly on fatty acid catabolism in the host. however,mtbalso maintains a functional glycolytic pathway and its role in the cellular metabolism ofmtbhas yet to be understood. pyruvate kinase catalyzes the last and rate-limiting step in glycolysis and themtbgenome harbors one putative pyruvate kinase (pyka, rv1617). here we show thatpyka ...201626858255
the structure of the transcriptional repressor kstr in complex with coa thioester cholesterol metabolites sheds light on the regulation of cholesterol catabolism in mycobacterium tuberculosis.cholesterol can be a major carbon source formycobacterium tuberculosisduring infection, both at an early stage in the macrophage phagosome and later within the necrotic granuloma. kstr is a highly conserved tetr family transcriptional repressor that regulates a large set of genes responsible for cholesterol catabolism. many genes in this regulon, includingkstr, are either induced during infection or are essential for survival ofm. tuberculosis in vivo in this study, we identified two ligands for ...201626858250
structure and functional properties of the active form of the proteolytic complex, clpp1p2, from mycobacterium tuberculosis.the clpp protease complex and its regulatory atpases, clpc1 and clpx, inmycobacterium tuberculosis(mtb) are essential and, therefore, promising drug targets. themtbclpp protease consists of two heptameric rings, one composed of clpp1 and the other of clpp2 subunits. formation of the enzymatically active clpp1p2 complex requires binding of n-blocked dipeptide activators. we have found a new potent activator, benzoyl-leucine-leucine (bz-ll), that binds with higher affinity and promotes 3-4-fold hi ...201626858247
resistance related metabolic pathways for drug target identification in mycobacterium tuberculosis.increasing resistance to anti-tuberculosis drugs has driven the need for developing new drugs. resources such as the tropical disease research (tdr) target database and assessdrugtarget can help to prioritize putative drug targets. hower, these resources do not necessarily map to metabolic pathways and the targets are not involved in dormancy. in this study, we specifically identify drug resistance pathways to allow known drug resistant mutations in one target to be offset by inhibiting another ...201626856535
whole genome analysis of an mdr beijing/w strain of mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid.mycobacterium tuberculosis (m.tb) is one of the most prevalent bacterial pathogens in the world. with geographical wide spread and hypervirulence, beijing/w family is the most successful m.tb lineage. china is a country of high tuberculosis (tb) and high multiple drug-resistant tb (mdr-tb) burden, and the beijing/w family strains take the largest share of mdr strains. to study the genetic basis of beijing/w family strains' virulence and drug resistance, we performed the whole genome sequencing o ...201626854371
systematic survey of serine hydrolase activity in mycobacterium tuberculosis defines changes associated with persistence.the transition from replication to non-replication underlies much of mycobacterium tuberculosis (mtb) pathogenesis, as non- or slowly replicating mtb are responsible for persistence and poor treatment outcomes. therapeutic targeting of non-replicating populations is a priority for tuberculosis treatment, but few drug targets in non-replicating mtb are currently known. here, we directly measured the activity of the highly diverse and druggable serine hydrolases (shs) during active replication and ...201626853625
recent tuberculosis diagnosis toward the end tb strategy.tuberculosis (tb) is an infectious bacterial disease caused by mycobacterium tuberculosis. despite global tb eradication efforts, it is still a global public health concern, especially in low- and middle-income countries. most of the active tb infections are curable with early diagnosis and appropriate treatment, but drug-resistant tb is difficult and expensive to treat in immunocompetent as well as immunocompromised individuals. thus, rapid, economic, and accurate point-of care tools for tb dia ...201626853124
diagnostic usefulness of t-cell based assays for tuberculous meningitis in hiv-uninfected patients.early diagnosis and treatment of tuberculous meningitis (tbm) is essential for a positive outcome, but sensitive, specific, and rapid diagnostic tests for tbm are lacking. we evaluated the diagnostic utility of enzyme-linked immunosorbent spot (elispot) assays in hiv-uninfected patients with suspected tbm.201626851800
effect of vitamin d3 on maturation and antigen-presenting function of dendritic cells treated with mycobacterium tuberculosis.to investigate the phenotypic characteristics and functional capability differences of mouse bone marrow-derived dendritic cells after stimulation with mycobacterium tuberculosis in the presence or absence of vitamin d3.201626851787
interaction between antimicrobial peptides and mycobacteria.mycobacteria can cause different severe health problems, including tuberculosis (tb). the treatment of tb with conventional antibiotics is successful, however, the number of multi-drug and extensively-drug resistant mycobacterium tuberculosis strains increases. moreover, many classical antimycobacterial antibiotics have severe side effects. therefore, antimicrobial peptides (amps) seem to be good candidates for new therapeutic strategies. on the one hand amps can be used as a single drug or in c ...201626851776
correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in mycobacterium tuberculosis.molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method.201626851609
nmr-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium.does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (gtb) during the window of implantation (woi) assist in improving the understanding of endometrial receptivity?201626851602
potential novel markers to discriminate between active and latent tuberculosis infection in chinese individuals.latent tuberculosis infection (ltbi) constitutes the main reservoir for reactivation tuberculosis. the finding of potential biomarkers for differentiating between tb and ltbi is very necessary. in this study, the immunological characteristics and potential diagnostic utility of rv2029c, rv2628 and rv1813c proteins were assessed. these three proteins stimulated pbmcs from elispot-positive ltbi subjects produced higher levels of ifn-γ in comparison with tb patients and elispot-negative healthy sub ...201626851588
mycobacterium tuberculosis pe9 protein has high activity binding peptides which inhibit target cell invasion.pe/ppe proteins are involved in several processes during mycobacterium tuberculosis (mtb) infection of target cells; studying them is extremely interesting as they are the only ones from the mycobacterium genus, they abound in pathogenic species such as mtb and their function remains yet unknown. the pe9 protein (rv1088) was characterised, the rv1088 gene was identified by pcr in mtb complex strains and its expression and localisation on mycobacterial surface was confirmed by western blot and im ...201626851205
generation and application of ssdna aptamers against glycolipid antigen manlam of mycobacterium tuberculosis for tb diagnosis.the development of effective mycobacterial antigen diagnostic reagents remains a high priority. mannose-capped lipoarabinomannan (manlam) is a lipoglycan serving as a major cell wall component. manlam is also an early released antigen in the blood circulation system during mycobacteria tuberculosis (m.tb) infection and is a perfect target antigen for tb diagnosis. in this study, ssdna aptamers "antibodies" against manlam of the predominant clinical epidemic m.tb beijing genotype strains were gen ...201626850356
structural insights into mycobacterium tuberculosis rv2671 protein as a dihydrofolate reductase functional analogue contributing to para-aminosalicylic acid resistance.mycobacterium tuberculosis (mtb) rv2671 is annotated as a 5-amino-6-ribitylamino-2,4(1h,3h)-pyrimidinedione 5'-phosphate (aropp) reductase (ribd) in the riboflavin biosynthetic pathway. recently, a strain of mtb with a mutation in the 5' untranslated region of rv2671, which resulted in its overexpression, was found to be resistant to dihydrofolate reductase (dhfr) inhibitors including the anti-mtb drug para-aminosalicylic acid (pas). in this study, a biochemical analysis of rv2671 showed that it ...201626848874
draft genome sequence of mycobacterium tuberculosis kt-0204, isolated in south korea.here, we describe the draft genome sequence of mycobacterium tuberculosis kt-0204, non-beijing family. this sequence will reveal genes related to the evolution and adaptation of m. tuberculosis kt-0204 in human hosts.201626847902
anti-inflammatory potential of ursolic acid in mycobacterium tuberculosis-sensitized and concanavalin a-stimulated cells.ursolic acid (3-β-3-hydroxy-urs-12-ene-28-oic-acid; ua) is a triterpenoid carboxylic acid with various pharmaceutical properties. it is commonly found in apples, basil, berries, rosemary, peppermint, lavender, oregano, thyme, hawthorn and prunes. in the present study, the activities of ua against the mycobacterium tuberculosis h37rv‑induced release of a panel of inflammatory cytokines, including tumor necrosis factor-α (tnf-α), interleukin (il)-1β and il-6 from raw 264.7 murine macrophages, a549 ...201626847129
[genotype mtbdr plus 1.0® for the detection of cross-resistance between isoniazide and ethionamide in isolates of multidrug-resistant mycobacterium tuberculosis].a variable proportion of isolates of multidrug-resistant mycobacterium tuberculosis also presents resistance to ethionamide. it is important to determine whether resistance to isoniazid is independent or crossed with resistance to ethionamide, given that this could lead to the re-evaluation of second-line anti-tuberculosis treatment. the genotype mtbdr plus ® molecular test is used for the detection of mdr-mtb, as it identifies mutations associated with resistance to isoniazide and could detect ...201626844443
a novel liposome adjuvant dpc mediates mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice.tuberculosis (tb) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. however, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for tb subunit vaccine. therefore, it is imperative to develop new adjuvant. here we reported an adjuvant composed of dimethyl dioctadecylammonium (dda), poly i:c and cholesterol (dpc for short). dda can form a kind of catio ...201626845736
treatment of mycobacterium tuberculosis-infected macrophages with poly(lactic-co-glycolic acid) microparticles drives nfκb and autophagy dependent bacillary killing.the emergence of multiple-drug-resistant tuberculosis (mdr-tb) has pushed our available repertoire of anti-tb therapies to the limit of effectiveness. this has increased the urgency to develop novel treatment modalities, and inhalable microparticle (mp) formulations are a promising option to target the site of infection. we have engineered poly(lactic-co-glycolic acid) (plga) mps which can carry a payload of anti-tb agents, and are successfully taken up by human alveolar macrophages. even withou ...201626894562
structure of the ectodomain of the electron transporter rv2874 from mycobacterium tuberculosis reveals a thioredoxin-like domain combined with a carbohydrate-binding module.the members of the ccda family are integral membrane proteins that use a disulfide cascade to transport electrons from the thioredoxin-thioredoxin reductase system in the interior of the cell into the extracytoplasmic space. the core transmembrane portion of this family is often elaborated with additional hydrophilic domains that act as adapters to deliver reducing potential to targets outside the cellular membrane. to investigate the function of family members in mycobacterium tuberculosis, the ...201626894533
crescentic glomerulonephritis associated with pulmonary tuberculosis.tuberculosis of kidney and urinary tract is caused by members of the mycobacterium tuberculosis complex. kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. we report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. patient was treated with corticosteroids, haemodialysis, intravenou ...201626894074
draft genome sequence of mycobacterium tuberculosis kt-0184, isolated in south korea.here, we describe the draft genome sequence of mycobacterium tuberculosis kt-0184, from the beijing family. this genome will provide insight into the evolution and adaptation of m. tuberculosis kt-0184 in human hosts.201626893431
sweet syndrome and disseminated mycobacterium tuberculosis infection. 201626891891
mycobacterium orygis-associated tuberculosis in free-ranging rhinoceros, nepal, 2015. 201626890310
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