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boosting bcg-primed responses with a subunit apa vaccine during the waning phase improves immunity and imparts protection against mycobacterium tuberculosis.heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. however, optimal timing to boost bcg-immunity using subunit vaccines remains unclear in clinical trials. here, we followed the adhesin apa-specific t-cell responses in bcg-primed mice and investigated its bcg-booster potential. the apa-specific t-cell response peaked 32-52 weeks after parenteral or mucosal bcg-priming but waned significantly by 78 weeks. a subunit-apa-boost during the contraction-pha ...201627173443
antibody detection tests for early diagnosis in tuberculous meningitis.tuberculous meningitis (tbm) is the most severe form of tuberculosis. microbiological confirmation is rare and treatment is often delayed. early diagnosis and immediate initiation of treatment are essential for effective tbm control. a systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against mycobacterium tuberculosis in the cerebrospinal fluid (csf), according to standard methods. test performance was summarized using a bivariate random-eff ...201627173078
synthesis and evaluation of the 2-aminothiazoles as anti-tubercular agents.the 2-aminothiazole series has anti-bacterial activity against the important global pathogen mycobacterium tuberculosis. we explored the nature of the activity by designing and synthesizing a large number of analogs and testing these for activity against m. tuberculosis, as well as eukaryotic cells. we determined that the c-2 position of the thiazole can accommodate a range of lipophilic substitutions, while both the c-4 position and the thiazole core are sensitive to change. the series has good ...201627171280
rapid detection of rifampicin- and isoniazid-resistant mycobacterium tuberculosis using taqman allelic discrimination.multidrug-resistant tuberculosis (mdr-tb) is a global problem that many countries are challenged with. rapid and accurate detection of mdr-tb is critical for appropriate treatment and controlling of tb. the aim of the present study was to evaluate the taqman allelic discrimination without minor groove binder (mgb) as a rapid, efficient, and low-cost method for detection of drug resistant strains of mycobacterium tuberculosis.201627169012
prevalence of pulmonary tuberculosis in young adult patients with type 1 diabetes mellitus in india.there is limited information on prevalence of pulmonary tuberculosis (ptb) in patients with type-1-diabetes. we assessed the prevalence of ptb in patients with type-1-diabetes attending the outpatient-clinic in a tertiary-care hospital.201627168934
practical approaches for mining frequent patterns in molecular datasets.pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. many of these issues stem from the low user- ...201627168722
resistant tuberculosis in maranhão, brazil: a case series.mycobacterium tuberculosis multidrug resistance, especially against rifampicin and isoniazid, places pulmonary tuberculosis in the list of emerging diseases. the misuse of therapeutic regimens is one of its main predisposing factors.201627145827
unravelling the secrets of mycobacterial cidality through the lens of antisense.one of the major impediments in anti-tubercular drug discovery is the lack of a robust grammar that governs the in-vitro to the in-vivo translation of efficacy. mycobacterium tuberculosis (mtb) is capable of growing both extracellular as well as intracellular; encountering various hostile conditions like acidic milieu, free radicals, starvation, oxygen deprivation, and immune effector mechanisms. unique survival strategies of mtb have prompted researchers to develop in-vitro equivalents to simul ...201627144597
novel cephalosporins selectively active on nonreplicating mycobacterium tuberculosis.we report two series of novel cephalosporins that are bactericidal to mycobacterium tuberculosis alone of the pathogens tested, which only kill m. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. the two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at c-2 of the cephalosporin ring system, a positio ...201627144688
a 22-year-old man with pleural tuberculosis associated hydropneumothorax: case report and literature review.a 22-year-old asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. a chest tube was placed. pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). pleural biopsy revealed acid-fast bacilli. given his persistent pleural effusion, he was given four doses of intrapleural tiss ...201627144114
high rate of drug resistance among tuberculous meningitis cases in shaanxi province, china.the clinical and mycobacterial features of tuberculous meningitis (tbm) cases in china are not well described; especially in western provinces with poor tuberculosis control. we prospectively enrolled patients in whom tbm was considered in shaanxi province, northwestern china, over a 2-year period (september 2010 to december 2012). cerebrospinal fluid specimens were cultured for mycobacterium tuberculosis; with phenotypic and genotypic drug susceptibility testing (dst), as well as genotyping of ...201627143630
effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.mycobacterium tuberculosis (mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. in this scenario, the use of usnic acid (ua), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (mdr-tb) therapy. thus the aim of this study was to evaluate the effect of the encapsulation of ua into liposomes, as well as its combination with antituberculous agents such as rif ...201627143488
[application of gene xpert mycobacterium tuberculosis dna and resistance to rifampicin assay in the rapid detection of tuberculosis in children].to detect mycobacterium tuberculosis (mtb) and rifampin resistance of the clinical specimens in children by xpert mtb dna and resistance to rifampicin(mtb/rif) detection system, and evaluate the application value of this method in children with tuberculosis.201627143080
case report: a student of asian origin with pott's disease.we describe a case report of a student of asian origin who presented with fever of unknown origin, cough, recent onset low back pain and weight loss. initial physical examination was unremarkable. laboratory results showed inflammation, but extensive testing for bacteriological and viral serology was negative. while the chest computed tomography (ct) scan did not show any abnormal findings, pelvic ct scan revealed an osteolytic sacral mass, with extension to the soft tissues and muscles, and con ...201627141824
characterization of the in vitro assembly of ftsz in arthrobacter strain a3 using light scattering.the self-assembly of ftsz, the bacterial homolog of tubulin, plays an essential role in cell division. light scattering technique is applied to real-time monitor the in vitro assembly of ftsz in arthrobacter strain a3, a newly isolated psychrotrophic bacterium. the critical concentration needed for the assembly is estimated as 6.7μm. the polymerization of ftsz in arthrobacter strain a3 requires both gtp and divalent metal ions, while salt is an unfavorable condition for the assembly. the ftsz po ...201627164494
methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens.adenoviruses represent the most widely used viral-vectored platform for vaccine design, showing a great potential in the fight against intracellular infectious diseases to which either there is a lack of effective vaccines or the traditional vaccination strategy is suboptimal. the extensive understanding of the molecular biology of adenoviruses has made the new technologies and reagents available to efficient generation of adenoviral-vectored vaccines for both preclinical and clinical evaluation ...201627162933
antibiotic resistance mechanisms in m. tuberculosis: an update.treatment of tuberculosis (tb) has been a therapeutic challenge because of not only the naturally high resistance level of mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6-9 months. although they are quite effective in treating drug susceptible tb, these lengthy treatments often lead to p ...201627161440
protocol for a population-based molecular epidemiology study of tuberculosis transmission in a high hiv-burden setting: the botswana kopanyo study.mycobacterium tuberculosis (mtb) is transmitted from person to person via airborne droplet nuclei. at the community level, mtb transmission depends on the exposure venue, infectiousness of the tuberculosis (tb) index case and the susceptibility of the index case's social network. people living with hiv infection are at high risk of tb, yet the factors associated with tb transmission within communities with high rates of tb and hiv are largely undocumented. the primary aim of the kopanyo study is ...201627160840
unraveling methylation changes of host macrophages in mycobacterium tuberculosis infection.to characterize at high resolution dna methylation changes of cytokines which occur in the genome of macrophages in association with mycobacterium tuberculosis (mtb) infection201627156630
strategies of genome editing in mycobacteria: achievements and challenges.tremendous amount of physiological and functional complexities acquired through decades of evolutionary pressure makes mycobacterium tuberculosis (mtb) one of the most dreadful microorganisms infecting humans from centuries. astonishing advances in genomics and genome editing tools substantially grew our knowledge about mtb as an organism but dramatically failed to completely understand it as a pathogen. though conventional tools based on homologous recombination, antisense, controlled proteolys ...201627156629
functional polymorphisms of the tlr7 and tlr8 genes contribute to mycobacterium tuberculosis infection.tuberculosis (tb) has recently re-emerged as a major global public health threat and mycobacterium tuberculosis (mtb) is a highly successful pathogen that evolved remarkable strategies to establish persistent infection. there is strong evidence that host genetic factors influence individual susceptibility to tb. in this study, we evaluated the associations between the tlr7 and tlr8 genetic polymorphisms and tb susceptibility in chinese individuals. the results demonstrated that the frequency of ...201627156628
molecular characterization of mycobacterium tuberculosis isolates from tanga, tanzania: first insight of miru-vntr and microarray-based spoligotyping in a high burden country.molecular typing of mycobacterium tuberculosis(mtb) has greatly enhanced the understanding of the population structure of mtb isolates and epidemiology of tuberculosis (tb). to characterize prevalent genotypes of mtb, microarrays‑based spoligotyping and mycobacterial interspersed repetitive unit‑variable number of tandem repeats (miru‑vntr) were applied on 80 isolates collected from primary health care facilities in tanga, north‑eastern tanzania. a total of 18 distinct spoligotypes were identifi ...201627156627
serial image analysis of mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary tb.faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (tb) but no method exists to quantify persisters in clinical samples. we used automated image analysis to assess whether studying growth characteristics of individual mycobacterium tuberculosis colonies from sputum on solid media during early tb treatment facilitates 'persister' phenotyping. as time to detection (ttd) in liquid culture inversely correlates with total bacterial load we also evaluated th ...201627156626
activity of nitazoxanide and tizoxanide against mycobacterium tuberculosis in vitro and in whole blood culture.nitazoxanide (ntz) and its metabolite tizoxanide (tiz) were studied as antimycobacterial agents in vitro (in mycobacterial growth indicator tube [mgit] cultures) and in a whole blood bactericidal assay. both ntz and tiz show high protein binding. in mgit cultures (albumin concentration = 78 μm), inhibition of mycobacterium tuberculosis growth occurred at total drug concentrations of ≥16 μg/ml, whereas in whole blood cultures (albumin concentration = 350 μm), ≥128 μg/ml was required. free drug fr ...201627156623
elevated serum 25-hydroxy (oh) vitamin d levels are associated with risk of tb progression in gambian adults.vitamin d is essential in the host defence against tuberculosis (tb) as an immune modulator. the aim of this study was to determine the level of 25-hydroxyvitamin d (25 (oh) d) from adult tb index cases before and after treatment and their exposed household contacts (hhc) in the gambia.201627156622
whole genome sequencing of mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: a systematic review.contact tracing complemented with genotyping is considered an important means of understanding person-to-person transmission of tuberculosis (tb). it still remains unclear whether whole genome sequencing (wgs) of mycobacterium tuberculosis can rule in transmission and how it performs in different human populations, risk groups and across tb lineages. this systematic review aimed to determine the sensitivity and specificity of wgs for detection of recent transmission using conventional epidemiolo ...201627156621
hiv-1 and the mycobacterium tuberculosis granuloma: a systematic review and meta-analysis.infection with hiv-1 greatly increases the risk of active tuberculosis (tb). although hypotheses suggest hiv-1 disrupts mycobacterium tuberculosis (mtb) granuloma function, few studies have examined this directly. the objective of this study was to determine what evidence exists about the effect hiv-1 co-infection has upon mtb granulomas. a systematic search of pubmed, web of science, and medline up to 20 march 2015 was conducted, to identify studies comparing mtb-infected tissue from hiv-1 infe ...201627156620
prevalence and transmission of pyrazinamide resistant mycobacterium tuberculosis in china.pyrazinamide (pza) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on pza resistant (pza-r) rate in china. from june 2009 to june 2012, we selected 493 isolates from five field settings in china to investigate pza-r by pnca gene sequencing. the result showed that pza-r rate was 1.0% (2/196) among pan-susceptible isolates, 3.1% (4/130) among isoniazid (inh) mono-resistant isolates, 14.0% (6/43) among rifampin (rif) mono-resistant isolates and 43 ...201627156619
longitudinal whole genome analysis of pre and post drug treatment mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.tuberculosis (tb) is one of the leading causes of death due to an infectious disease in the world. understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant tb cases. we have analyzed three pairs of mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. in the rifampicin resistant strain, we confirmed a mutation in rpo ...201627156618
cloning, expression and characterization of histidine-tagged biotin synthase of mycobacterium tuberculosis.the emergence of mycobacterium tuberculosis strains that are resistant to the current anti-tuberculosis (tb) drugs necessitates a need to develop a new class of drugs whose targets are different from the current ones. m. tuberculosis biotin synthase (mtbbs) is one such target that is essential for the survival of the bacteria. in this study, mtbbs was cloned, overexpressed and purified to homogeneity for biochemical characterization. it is likely to be a dimer in its native form. its ph and temp ...201627156617
mycobacterium tuberculosis infection and vaccine development.following hiv/aids, tuberculosis (tb) continues to be the second most deadly infectious disease in humans. the global tb prevalence has become worse in recent years due to the emergence of multi-drug resistant (mdr) and extensively-drug resistant (xdr) strains, as well as co-infection with hiv. although bacillus calmette-guérin (bcg) vaccine has nearly been used for a century in many countries, it does not protect adult pulmonary tuberculosis and even causes disseminated bcg disease in hiv-posit ...201627156616
neuroleptic drugs in the treatment of tuberculosis: minimal inhibitory concentrations of different phenothiazines against mycobacterium tuberculosis.due to an increase of drug resistant tb, alternative drugs that are not currently listed in the who guidelines on mdr tb treatment are currently being evaluated. our group tested 100 susceptible, 20 mdr and 2 xdr mtb strains against the phenothiazine derivatives thioridazine, trifluoperazine and triflupromazine. mic testing was performed on middlebrook 7h10 agar and was defined as the lowest drug concentration that inhibits ≥99% of the bacterial population. we confirm very good in vitro activity ...201627156615
tuberculosis or sarcoidosis: opposite ends of the same disease spectrum?tuberculosis and sarcoidosis are chronic systemic diseases that have similar pulmonary and extra-pulmonary manifestations. multiple studies have found an epidemiological, molecular, and immunological link between the two. it has been suggested that mycobacterium tuberculosis could be a common pathophysiologic mechanism for tuberculosis and sarcoidosis, and that both clinical entities can trigger similar immunological response in patients. due to this close association, together with possible coe ...201627156614
impaired nk cells' activity and increased numbers of cd4 + cd25+ regulatory t cells in multidrug-resistant mycobacterium tuberculosis patients.multidrug-resistant tuberculosis (mdr-tb) often causes persistent infection and chemotherapy failure, which brings heavy burden of society and family. many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. the presence of regulatory t cells (tregs) is thought to be an important mechanism that tb successfully evades the immune system. tregs play a central role in the prevention of autoimmunity and in the control of immune responses. the role of ...201627156613
thermostability of ifn-γ and ip-10 release assays for latent infection with mycobacterium tuberculosis: a tbnet study.interferon-γ (ifn-γ) inducible protein 10kd (ip-10) and ifn-γ release assays (igras) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with mycobacterium tuberculosis. incubation at higher temperatures could affect ifn-γ and ip-10 responsiveness in order to improve the performance of ip-10 release assays and igras.201627156612
insights into rpob clinical mutants in mediating rifampicin resistance in mycobacterium tuberculosis.rifampicin (rif) an essential first-line anti-tuberculosis (tb) drug, resistance to rif is a potential threat to tb control program and widely considered as surrogate marker for detection of multi-drug resistant-tb (mdr-tb), molecular understanding of which is the utmost need of the hour. mutations at rif resistance-determining region (rrdr) of 81-bp in the rpob gene coding for β subunit or rpob protein is the major cause of rif resistance in mycobacterium tuberculosis (mtb). mutation at positio ...201627155814
does concurrent use of some botanicals interfere with treatment of tuberculosis?millions of individuals with active tb do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of tb, as suggested by results of a recent clinical trial of the south african botanical sutherlandia frutescens (l.) r. br. (sutherlandia). here we provide a ...201627155670
distribution and association of mycobacterium tuberculosis cas lineage with multidrug resistance in north india.a tertiary care hospital in north india.201627155185
capilia™ tb-neo assay: a new tool for rapid distinction between tuberculous and non-tuberculous mycobacteria.the ability to rapidly distinguish between mycobacterium tuberculosis complex (mtc) and non-tuberculous mycobacteria (ntm) is critical in clinical practice.201627155177
host immune responses to antigens derived from a predominant strain of mycobacterium tuberculosis.beijing strain of mycobacterium tuberculosis (m. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. this study aimed to determine host immune responses to antigens derived from the beijing/k strain which has been highly prevalent in tuberculosis (tb) outbreaks in south korea.201627155519
immune oxysterols: role in mycobacterial infection and inflammation.infection remains an important cause of morbidity and mortality. natural defenses to infection are mediated by intrinsic/innate and adaptive immune responses. while our understanding is considerable it is incomplete and emerging areas of research such as those related to the immune-metabolic axis are only beginning to be appreciated. there is increasing evidence showing a connection between immune signalling and the regulation of sterol and fatty acid metabolism. in particular, metabolic interme ...201627155346
early secreted antigenic target of 6 kda of mycobacterium tuberculosis stimulates macrophage chemoattractant protein-1 production by macrophages and its regulation by p38 mitogen-activated protein kinases and interleukin-4.early secreted antigenic target of 6 kda (esat-6), the major virulence factor of mycobacterium tuberculosis, affects host immunity and the formation of granulomas likely through inflammatory cytokines. to understand its role in this regard further, we investigated the effect of esat-6 on macrophages by determining the production of macrophage chemoattractant protein (mcp)-1, a major chemokine associated with tuberculosis pathogenesis, by murine bone marrow-derived macrophages (bmdms) and its reg ...201627154637
improving the n-terminal diversity of sansanmycin through mutasynthesis.sansanmycins are uridyl peptide antibiotics (upas), which are inhibitors of translocase i (mray) and block the bacterial cell wall biosynthesis. they have good antibacterial activity against pseudomonas aeruginosa and mycobacterium tuberculosis strains. the biosynthetic gene cluster of sansanmycins has been characterized and the main biosynthetic pathway elucidated according to that of pacidamycins which were catalyzed by nonribosomal peptide synthetases (nrpss). sananmycin a is the major compou ...201627154005
new agents for the treatment of drug-resistant mycobacterium tuberculosis.inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (mdr-tb). treatment of mdr-tb infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. this review focuses on emerging drug classes that have the potential for treating mdr-t ...201627151308
repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs.the number of cases of drug-resistant mycobacterium tuberculosis, the causative agent of tuberculosis (tb), has risen rapidly in recent years. this has led to the resurgence in repurposing existing drugs, such as non-steroidal anti-inflammatory drugs (nsaids), for anti-tb treatment.201627151954
comparative proteomic analyses of avirulent, virulent, and clinical strains of mycobacterium tuberculosis identify strain-specific patterns.mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. here, we report systematic proteomic analyses of four strains, h37ra, h37rv, and clinical isolates bnd and jal, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 prot ...201627151218
sulphur-containing heterocycles as antimycobacterial agents: recent advances in thiophene and thiadiazole derivatives.the global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. recent development is focused mainly on heterocyclic molecules. in many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. this review highlights the recent progress ...201627150373
mapping of mycobacterium tuberculosis complex genetic diversity profiles in tanzania and other african countries.the aim of this study was to assess and characterize mycobacterium tuberculosis complex (mtbc) genotypic diversity in tanzania, as well as in neighbouring east and other several african countries. we used spoligotyping to identify a total of 293 m. tuberculosis clinical isolates (one isolate per patient) collected in the bunda, dar es salaam, ngorongoro and serengeti areas in tanzania. the results were compared with results in the sitvit2 international database of the pasteur institute of guadel ...201627149626
identification of a non-pentapeptide region associated with rapid mycobacterial evolution.a large portion of the coding capacity of mycobacterium tuberculosis is devoted to the production of proteins containing several copies of the pentapeptide-2 repeat, namely the pe/ppe_mptr proteins. protein domain repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as dna and rna. they are not as common in prokaryotes, compared to eukaryotes, but the enrichment of pentapeptide-2 repeats in mycobacteria constitutes ...201627149271
g1-4a, a polysaccharide from tinospora cordifolia inhibits the survival of mycobacterium tuberculosis by modulating host immune responses in tlr4 dependent manner.rapid emergence of drug resistance in mycobacterium tuberculosis (mtb) is a major health concern and demands the development of novel adjunct immunotherapeutic agents capable of modulating the host immune responses in order to control the pathogen. in the present study, we sought to investigate the immunomodulatory effects of g1-4a, a polysaccharide derived from the indian medicinal plant tinospora cordifolia, in in-vitro and aerosol mouse models of mtb infection. g1-4a treatment of mtb infected ...201627148868
benzothiazole derivative as a novel mycobacterium tuberculosis shikimate kinase inhibitor: identification and elucidation of its allosteric mode of inhibition.mycobacterium tuberculosis shikimate kinase (mtb-sk) is a key enzyme involved in the biosynthesis of aromatic amino acids through the shikimate pathway. since it is proven to be essential for the survival of the microbe and is absent from mammals, it is a promising target for anti-tb drug discovery. in this study, a combined approach of in silico similarity search and pharmacophore building using already reported inhibitors was used to screen a procured library of 20,000 compounds of the commerc ...201627149193
immunometabolism in tuberculosis.immunometabolism, the study of the relationship between bioenergetic pathways and specific functions of immune cells, has recently gained increasing appreciation. in response to infection, activation of the host innate and adaptive immune cells is accompanied by a switch in the bioenergetic pathway from oxidative phosphorylation to glycolysis, a metabolic remodeling known as the warburg effect, which is required for the production of antimicrobial and pro-inflammatory effector molecules. in this ...201627148269
insufficient generation of mycobactericidal mediators and inadequate level of phagosomal maturation are related with susceptibility to virulent mycobacterium tuberculosis infection in mouse macrophages.tuberculosis is caused by mycobacterium tuberculosis infection, and it remains major life-threatening infectious diseases worldwide. although, m. tuberculosis has infected one-third of the present human population, only 5-10% of immunocompetent individuals are genetically susceptible to tuberculosis. all inbred strains of mice are susceptible to tuberculosis; however, some mouse strains are much more susceptible than others. in a previous report, we showed that th1-mediated immunity was not resp ...201627148227
mycobacterium tuberculosis pe13 (rv1195) manipulates the host cell fate via p38-erk-nf-κb axis and apoptosis.pe/ppe family proteins are mycobacteria unique molecules, named after their n-terminal conserved pe (pro-glu) and ppe (pro-pro-glu) domains. mycobacterium tuberculosis (mtb) pe family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. to explore the role of a novel pe member (pe13, rv1195), m. smegmatis was used as surrogate host. the study showed that rv1195 was a cell wall associated protein. rv1195 can enhance the survival of reco ...201627147522
identification of potential antituberculosis drugs through docking and virtual screening.tuberculosis is the most prominent contagious disease and needs the new targets and drugs identification. target identification and validation is a crucial step in drug discovery process. in mycobacterium tuberculosis, decaprenyl-phosphoryl-β-d-ribose 2'-oxidase is a potential target for antitubercular chemotherapy. it is encoded by genes dpre1 (rv3790) and dpre2 (rv3791). three-dimensional (3d) structure prediction of selected target (461 amino acid residues) was intent by homology modeling usi ...201627147082
anti-tubercular and antioxidant activities of c-glycosyl carbonic anhydrase inhibitors: towards the development of novel chemotherapeutic agents against mycobacterium tuberculosis.during the treatment of tuberculosis infection, oxidative stress due to anti-tubercular drugs may result in tissue inflammation. it was suggested that treatment with antioxidant drugs could be beneficial as an adjunct to anti-tuberculosis drug therapy. recently our group has shown that several c-glycosides are inhibitors of mycobacterium tuberculosis β-carbonic anhydrases (cas, ec 4.2.1.1). in an effort to develop novel chemotherapeutic agents against tuberculosis, the anti-tubercular and antiox ...201627146440
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
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
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
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
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