Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
mycobacterium tuberculosis rv2185c contributes to nuclear factor-κb activation.tuberculosis caused by mycobacterium tuberculosis has a detrimental impact on public health worldwide, especially in developing countries. the nuclear factor-κb (nf-κb) signaling pathway is reportedly involved in the innate immune response against m. tuberculosis infections. we screened the secreted proteins, membrane proteins, and lipoproteins of the m. tuberculosis h37rv strain using luciferase activity assays. the rv2185c protein exhibited the potential to activate nf-κb in hela and a549 cell ...201525771181
discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.a new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-tb) against mycobacterium tuberculosis. molecular modeling, pharmacophore constructed using galahad to produce an effective alignment of data set and evaluated by pareto ranking. the pharmacophore features were filtered by surflex-dock study using enoyl acp reductase from m. tuberculosis, which is one of the key enzymes involved in type ii fatty acid biosynthesis p ...201525771110
synthesis, crystal structure and biological evaluation of substituted quinazolinone benzoates as novel antituberculosis agents targeting acetohydroxyacid synthase.acetohydroxyacid synthase (ahas) catalyzes the first essential biosynthetic step of branched-chain amino acids and is a biologically safe target against mycobacterium tuberculosis (mtb). in our previous research, we used virtual screening to identify some novel ahas inhibitors as potent antituberculosis agents. in this study, we synthesized twenty-four additional quinazolinone benzoates and explored their antitubercular activity. five of these compounds displayed significant mtb-ahas inhibition ...201525771108
nanomolar inhibitors of mycobacterium tuberculosis glutamine synthetase 1: synthesis, biological evaluation and x-ray crystallographic studies.a series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit m. tuberculosis glutamine synthetase (glna1) has been identified by high throughput screening. exploration of this series was performed owing to a short chemistry program. despite possibly nanomolar inhibitions, none of these compounds was active on whole cell mtb, suggesting that glna1 may not be a suitable target to find new anti-tubercular drugs.201525770781
confirming mycobacterium tuberculosis transmission from a cadaver to an embalmer using molecular epidemiology.genotyping results and epidemiologic investigation were used to confirm tuberculosis transmission from a cadaver to an embalmer. this investigation highlights the utility of genotyping in identifying unsuspected epidemiologic links and unusual transmission settings. in addition, the investigation provides additional evidence for the occupational risk of tuberculosis among funeral service workers and indicates a need for education about tuberculosis risk and the importance of adhering to appropri ...201525769616
identification of potential mycobacterium tuberculosis topoisomerase i inhibitors: a study against active, dormant and resistant tuberculosis.mycobacterium tuberculosis (mtb) topoisomerase i (topo i), involved in the relaxation of negatively supercoiled dna, plays an important role in the viability of pathogen mtb. being one of the most significant enzymes; it also takes part in crucial biological pathways such as transcription and replication of the pathogen. the present study aims at the development of mtb topo i 3d protein structure which in turn was employed for the virtual screening of compound libraries in a process of identific ...201525769524
prevalence and occurrence rate of mycobacterium tuberculosis haarlem family multi-drug resistant in the worldwide population: a systematic review and meta-analysis.transmission of mycobacterium tuberculosis (m. tuberculosis) can occur in different ways. furthermore, drug resistant in m. tuberculosis family is a major problem that creates obstacles in treatment and control of tuberculosis (tb) in the world. one of the most prevalent families of m. tuberculosis is haarlem, and it is associated with drug resistant. our objectives of this study were to determine the prevalence and occurrence rate of m. tuberculosis haarlem family multi-drug resistant (mdr) in ...201525767526
rapid diagnosis of pleural tuberculosis by xpert mtb/rif assay using pleural biopsy and pleural fluid specimens.early pleural tuberculosis (tb) diagnosis is particularly difficult. the aim of this study was to investigate the diagnostic accuracy of the xpert mtb/rif (xpert) (cepheid, sunnyvale, ca) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural tb but who had a negative sputum acid-fast bacilli (afb) smear.201525767518
comparing mycobacterium tuberculosis genomes using genome topology networks.over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. several findings have revealed that genomic structural variations (svs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by svs may extend our knowledge of the relationships between svs an ...201525766780
a murine monoclonal antibody to glycogen: characterization of epitope-fine specificity by saturation transfer difference (std) nmr spectroscopy and its use in mycobacterial capsular α-glucan research.mycobacterium tuberculosis, the causative agent of tuberculosis (tb), is a major pathogen responsible for 1.5 million deaths annually. this bacterium is characterized by a highly unusual and impermeable cell envelope, which plays a key role in mycobacterial survival and virulence. although many studies have focused on the composition and functioning of the mycobacterial cell envelope, the capsular α-glucan has received relatively minor attention. here we show that a murine monoclonal antibody (m ...201525766777
nanocarrier-based interventions for the management of mdr/xdr-tb.emergence of multidrug-resistant tb (mdr-tb) and extensively drug-resistant tb over the past decade presents an unprecedented public health challenge to which countries of concern are responding far too slowly. global tuberculosis report 2014 marks the 20th anniversary of the global project on anti-tuberculosis drug resistance surveillance, indicating the highest global level of drug-resistance ever recorded detection of 97 000 patients with mdr-tb resulting in 170 000 deaths in 2013. treatment ...201525766078
advancing host-directed therapy for tuberculosis.improved treatments are needed for nearly all forms of mycobacterium tuberculosis infection. adjunctive host-directed therapies have the potential to shorten tuberculosis treatment duration, prevent resistance and reduce lung injury by promoting autophagy, antimicrobial peptide production and other macrophage effector mechanisms, as well as by modifying specific mechanisms that cause lung inflammation and matrix destruction. the range of candidates is broad, including several agents approved for ...201525765201
integration of published information into a resistance-associated mutation database for mycobacterium tuberculosis.tuberculosis remains a major global public health challenge. although incidence is decreasing, the proportion of drug-resistant cases is increasing. technical and operational complexities prevent mycobacterium tuberculosis drug susceptibility phenotyping in the vast majority of new and retreatment cases. the advent of molecular technologies provides an opportunity to obtain results rapidly as compared to phenotypic culture. however, correlations between genetic mutations and resistance to multip ...201525765106
tuberculosis diagnostics in 2015: landscape, priorities, needs, and prospects.in 2015, tuberculosis remains a major global health problem, and drug-resistant tuberculosis is a growing threat. although tuberculosis diagnosis in many countries is still reliant on older tools, new diagnostics are changing the landscape. stimulated, in part, by the success and roll out of xpert mtb/rif, there is now considerable interest in new technologies. the landscape looks promising, with a robust pipeline of new tools, particularly molecular diagnostics, and well over 50 companies activ ...201525765103
ethambutol-related impaired visual function in childrens less than 5 years of age treated for a mycobacterial infection: diagnosis and evolution.the effects of ethambutol (emb) on vision are particularly difficult to detect in children less than 5 years of age because of a lack of complaints and objective clinical signs. the aim of this study was to assess the frequency of visual abnormalities and the utility of visual-evoked potentials (veps) recordings in monitoring the visual function of children less than 5 years of age who were exposed to emb during anti-mycobacterial treatment.201525764095
risk assessment of tuberculosis in contacts by ifn-γ release assays. a tuberculosis network european trials group study.latent infection with mycobacterium tuberculosis is defined by a positive ifn-γ release assay (igra) result in the absence of active tuberculosis. only few, mostly monocentric studies have evaluated the role of igras to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis.201525763458
transcriptional adaptation of drug-tolerant mycobacterium tuberculosis during treatment of human tuberculosis.treatment initiation rapidly kills most drug-susceptible mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. we evaluated drug-tolerant bacilli in human sputum by comparing messenger rna (mrna) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli.201525762787
macrophages are needed in the progression of tuberculosis into lung cancer.although the association of tuberculosis (tb) and the development of lung carcinoma (lc) has been acknowledged, the underlying mechanism remains not clarified. since sustained and repeated local inflammation and tissue remodeling have been suggested to be responsible for the high incidence of developing cl from tb, we hypothesize that macrophages may play a critical role in the process. to prove it, we induced tb in mice by injection of virulent mycobacterium tuberculosis (mtb). then the mice we ...201525761875
no strong relationship between components of the lectin pathway of complement and susceptibility to pulmonary tuberculosis.mycobacterium tuberculosis (tb) may utilise the lectin complement pathway to facilitate entry into its niche within macrophages. previous studies examining mannose-binding lectin (mbl) in patients with tb have been limited by failure to correlate genotype/phenotype relationships. this study investigated serum levels and genotypes of mbl, ficolin-2, ficolin-3 and masp-2 in 168 patients with pulmonary tuberculosis and 168 age/sex-matched controls. low serum levels of mbl and ficolin-2 were defined ...201525761428
crystallization and preliminary x-ray analysis of rv1674c from mycobacterium tuberculosis.adaptations to hypoxia play an important role in mycobacterium tuberculosis pathogenesis. rv0324, which contains an hth dna-binding domain and a rhodanese domain, is one of the key transcription regulators in response to hypoxia. m. tuberculosis rv1674c is a homologue of rv0324. to understand the interdomain interaction and regulation of the hth domain and the rhodanese domain, recombinant rv1674c protein was purified and crystallized by the vapour-diffusion method. the crystals diffracted to 2. ...201525760714
engineering more stable, selectable marker-free autoluminescent mycobacteria by one step.in our previous study, we demonstrated that the use of the autoluminescent mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. however, the strains were relatively unstable and lost reporter with time without selection. the kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important cla ...201525760622
mycobacteriophages: an important tool for the diagnosis of mycobacterium tuberculosis (review).the prevention and control of tuberculosis (tb) on a global scale has become increasingly important with the emergence of multidrug‑resistant tb. mycobacterium tuberculosis phages have been identified as an important investigative tool. phage genomes exhibit a significant level of diversity and mosaic genome architecture, however, they are simple structures, which are amenable to genetic manipulation. based on these characteristics, the phages may be used to construct a shuttle plasmid, which is ...201525760591
drug-resistant tuberculosis can be predicted by mycobacterial interspersed repetitive unit locus.it is unknown whether miru-vntr (mycobacterial interspersed repetitive unit-variable number of tandem repeat) is associated with drug resistance of mycobacterium tuberculosis. the purpose of this study was to explore the ability of 24 miru loci to predict the drug resistance of isoniazid (inh), rifampicin (rfp), streptomycin (sm), ethambutol (emb) and pyrazinamide (pza). we collected the drug resistance and miru loci information of 109 strains of m. tuberculosis from an open database. the result ...201525759689
cleavage specificity of mycobacterium tuberculosis clpp1p2 protease and identification of novel peptide substrates and boronate inhibitors with anti-bacterial activity.the clpp1p2 protease complex is essential for viability in mycobacteria tuberculosis and is an attractive drug target. using a fluorogenic tripeptide library (ac-x3x2x1-aminomethylcoumarin) and by determining specificity constants (kcat/km), we show that clpp1p2 prefers met ≫ leu > phe > ala in the x1 position, basic residues or trp in the x2 position, and pro ≫ ala > trp in the x3 position. we identified peptide substrates that are hydrolyzed up to 1000 times faster than the standard clpp subst ...201525759383
[tuberculosis surveillance in sicily, italy].to describe the epidemiology of tuberculosis (tb) in sicily in the years 2010-2013.201525759350
hi-jack: a novel computational framework for pathway-based inference of host-pathogen interactions.pathogens infect their host and hijack the host machinery to produce more progeny pathogens. obligate intracellular pathogens, in particular, require resources of the host to replicate. therefore, infections by these pathogens lead to alterations in the metabolism of the host, shifting in favor of pathogen protein production. some computational identification of mechanisms of host-pathogen interactions have been proposed, but it seems the problem has yet to be approached from the metabolite-hija ...201525758402
transmissibility of tuberculosis among school contacts: an outbreak investigation in a boarding middle school, china.tuberculosis (tb) outbreak occurred in a boarding middle school of china. we explored its probable sources and quantified the transmissibility and pathogenicity of tb. clinical evaluation, tuberculin skin testing and chest radiography were conducted to identify tb cases. mycobacterium tuberculosis isolates underwent genotyping analysis to identify the outbreak source. a chain-binomial transmission model was used to evaluate transmissibility and pathogenicity of tb. a total of 46 active cases wer ...201525757905
delamanid for the treatment of pulmonary multidrug-resistant tuberculosis.out of a handful of new drugs currently in clinical trials for the treatment of tuberculosis, delamanid, a nitro-dihydro-imidazole derivative, has successfully emerged. delamanid is a novel mycolic acid biosynthesis inhibitor that is equally potent against drug-sensitive as well as drug-resistant mycobacterium tuberculosis. one of the strongest points for delamanid is its inability to be metabolized by cytochrome p450 enzymes, making it a promising candidate to be used in combination therapies f ...201525756067
exogenous reinfection of tuberculosis in a low-burden area.recurrence of tuberculosis (tb) can be the consequence of relapse or exogenous reinfection. the study aimed to assess the factors associated with exogenous tb reinfection.201525754899
synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives.tuberculosis (tb) remains a major human health problem. new therapeutic antitubercular agents are urgent needed to control the global tuberculosis pandemic. we synthesized a new series of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives and evaluated their anti-mycobacterial activities against mycobacterium tuberculosis h37ra as well as their druggabilities. the results showed that most of these derivatives, especially the compounds with simple alkyl side chains, exhibited go ...201525754492
mycobacterium tuberculosis phylogeography in the context of human migration and pathogen's pathobiology: insights from beijing and ural families.here, i review the population structure and phylogeography of the two contrasting families of mycobacterium tuberculosis, beijing and ural, in the context of strain pathobiology and human history and migration. proprietary database (12-loci miru-vntr profiles of 3067 beijing genotype isolates) was subjected to phylogenetic and statistical analysis. the highest rate (90%) and diversity (hgi 0.80-0.95) of the beijing genotype in north china suggest it to be its area of origin. under vntr-based mds ...201525754342
evidence for tuberculosis in 18th/19th century slaves in anse sainte-marguerite (guadeloupe - french western indies).during the american colonization in the 18th and 19th century, africans were captured and shipped to america. harsh living and working conditions often led to chronic diseases and high mortality rates. slaves in the caribbean were forced to work mainly on sugar plantations. they were buried in cemeteries like anse sainte-marguerite on the isle of grande-terre (guadeloupe) which was examined by archaeologists and physical anthropologists. morphological studies on osseous remains of 148 individual ...201525754341
three-dimensional imaging of past skeletal tb: from lesion to process.3d imaging has become an essential tool in the field of biological anthropology, notably for human evolution purposes. high resolution virtual 3d reconstructions of original specimens contribute to their preservation and broaden the ability for research, teaching and exchanges. paleopathology can get substantial benefit from these methods, among others for reconstructing infectious pathological processes on ancient bones. tuberculosis is frequently diagnosed on ancient human remains; however, so ...201525754340
exosomal rna from mycobacterium tuberculosis-infected cells is functional in recipient macrophages.exosomes are extracellular vesicles released by cells that carry proteins, lipids and nucleic acids and function in intercellular communication. previously, we determined that exosomes released from mycobacterium tuberculosis (m.tb)-infected macrophages carry mycobacterial proteins and lipids. however, the rna composition within these exosomes has not been defined. in this study, we characterized the exosomes released from m.tb-infected macrophages and identified a cohort of mouse messenger rna ...201525753779
pharmacokinetics and pharmacodynamics of clofazimine in a mouse model of tuberculosis.the antileprosy drug clofazimine has shown potential for shortening tuberculosis treatment; however, the current dosing of the drug is not evidence based, and the optimal dosing is unknown. our objective was to conduct a preclinical evaluation of the pharmacokinetics and pharmacodynamics of clofazimine in the mouse model of tuberculosis, with the goal of providing useful information on dosing for future studies. pharmacokinetic parameters were evaluated in infected and uninfected balb/c mice. ph ...201525753644
identification of mir-93 as a suitable mir for normalizing mirna in plasma of tuberculosis patients.tuberculosis (tb) remains a major public health issue. new tests to aid diagnoses and monitor the response to therapy are urgently required. there is growing interest in the use of microrna (mirna) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including mycobacterium tuberculosis infection, however, challenges exist to accurately normalise mirna levels in cohorts. this study examined the appropriateness of 12 mirs and rnu6b to normalise ...201525753045
compounds for use in the treatment of mycobacterial infections: a patent evaluation (wo2014049107a1).tuberculosis is one of the main causes of mortality with 1.5 million deaths a year worldwide. the growing emergence of multi- and extremely resistant strains highlights the urgent need of novel antibiotic strategies. ethionamide, interfering with the mycobacterial membrane biosynthesis, is used in second-line treatment. this molecule is a prodrug, which requires activation by etha. the patent described in this evaluation (wo2014049107a1) claimed a new family of molecules and their use as antibio ...201525752488
the glyoxylate shunt is essential for co2-requiring oligotrophic growth of rhodococcus erythropolis n9t-4.rhodococcus erythropolis n9t-4 shows extremely oligotrophic growth requiring atmospheric co2 and forms its colonies on an inorganic basal medium (bm) without any additional carbon source. screening of a random mutation library constructed by a unique genome deletion method that we established indicated that the acea, aceb, and pckg genes encoding isocitrate lyase, malate synthase, and phosphoenolpyruvate carboxykinase, respectively, were requisite for survival on bm plates. the acea- and aceb de ...201525750047
imaging chronic tuberculous lesions using sodium [(18)f]fluoride positron emission tomography in mice.calcification is a hallmark of chronic tuberculosis (tb) in humans, often noted years to decades (after the initial infection) on chest radiography, but not visualized well with traditional positron emission tomography (pet). we hypothesized that sodium [(18)f]fluoride (na[(18)f]f) pet could be used to detect microcalcifications in a chronically mycobacterium tuberculosis-infected murine model.201525750032
[primary infection and pulmonary tuberculosis].tuberculosis is a major public health problem worldwide. indeed, a third of the world population is infected with mycobacterium tuberculosis and more than 8 million new cases of tuberculosis each year. pulmonary tuberculosis is the most common location. its diagnosis is difficult and often established with a delay causing a spread of infection. the diagnosis of tuberculosis infection is mainly based on immunological tests represented by the tuberculin skin test and detection of gamma interferon, ...201525749628
defining multidrug-resistant tuberculosis: correlating genotype mtbdrplus assay results with minimum inhibitory concentrations.this study correlates mics of rifampicin (rif) and isoniazid (inh) with genotype mtbdrplus assay results for drug-resistant mycobacterium tuberculosis (mtb) clinical isolates. mics of rif and inh were established for 84 and 90 isolates, respectively, testing 7 concentrations of each drug. genotypic resistance to each drug was determined by genotype mtbdrplus assay with 50 representative mutations confirmed by pyrosequencing, with mutations in the rpob gene associated with rif resistance and muta ...201525749461
critical determinants for substrate recognition and catalysis in the m. tuberculosis class ii ap-endonuclease/3'-5' exonuclease iii.the mycobacterium tuberculosis ap-endonuclease/3'-5' exodeoxyribonuclease (mtbxtha) is an important player in dna base excision repair (ber). we demonstrate that the enzyme has robust apurinic/apyrimidinic (ap) endonuclease activity, 3'-5' exonuclease, phosphatase, and phosphodiesterase activities. the enzyme functions as an ap-endonuclease at high ionic environments, while the 3'-5'-exonuclease activity is predominant at low ionic environments. our molecular modelling and mutational experiments ...201525748880
lung mucosa lining fluid modification of mycobacterium tuberculosis to reprogram human neutrophil killing mechanisms.we have shown that human alveolar lining fluid (alf) contains homeostatic hydrolases capable of altering the mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. neutrophils are also an integral part of the host immune response to m. tuberculosis infection. here we show that the human lung mucosa influences m. tuberculosis interaction with neutrophils, enhancing the intracellular killing of alf-exposed m. tuberculosis and up-regulating the expression of t ...201525748325
clustured regularly interspersed short palindromic repeats (crispr) genetic diversity studies as a mean to reconstruct the evolution of the mycobacterium tuberculosis complex.the natural history of tuberculosis may be tackled by various means, among which the record of molecular scars that have been registered by the mycobacterium tuberculosis complex (mtbc) genomes transmitted from patient to patient for tens of thousands years and possibly more. recently discovered polymorphic loci, the crispr sequences, are indirect witnesses of the historical phage-bacteria struggle, and may be related to the time when the ancestor of today's tubercle bacilli were environmental b ...201525748060
mycobacterium tuberculosis infection may provide an antigenic stimulus enabling children to mount a strong immune cell response. 201525746604
pyrazinamide: the importance of uncovering the mechanisms of action in mycobacteria.pyrazinamide (pza) is still one of the key drugs used in current therapeutic regimens for tuberculosis (tb). despite its importance for tb therapy, the mode of action of pza remains unknown. pza has to be converted to its active form pyrazinoic acid (poa) by the nicotinamidase pnca and is then excreted by an unknown efflux pump. at acidic conditions, poa is protonated to hpoa and is reabsorbed into the cell where it causes cellular damage. for a long time, it has been thought that pza/poa has no ...201525746054
bilateral choroidal tuberculoma in miliary tuberculosis - report of a case.a choroidal mass or granuloma is a feature of ocular tuberculosis (tb). tubercles can arise in the early stages of progression of tb and indicate hematogenous dissemination before the development of symptomatic disease. tubercular subretinal granuloma is responsive to treatment with anti-tuberculosis therapy, and prompt treatment helps resolve the lesion completely.201525861395
selective mycobacterium tuberculosis shikimate kinase inhibitors as potential antibacterials.owing to the persistence of tuberculosis (tb) as well as the emergence of multidrug-resistant and extensively drug-resistant (xdr) forms of the disease, the development of new antitubercular drugs is crucial. developing inhibitors of shikimate kinase (sk) in the shikimate pathway will provide a selective target for antitubercular agents. many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit sk. to a much more limited extent, sk inhibi ...201525861218
biochemical analysis of the nad+-dependent malate dehydrogenase, a substrate of several serine/threonine protein kinases of mycobacterium tuberculosis.pknd is one of the eleven eukaryotic-like serine/threonine protein kinases (stpks) of mycobacterium tuberculosis (mtb). in vitro phosphorylation assays with the active recombinant pknd showed that the intracellular protein nad+-dependent malate dehydrogenase (mdh) is a substrate of this kinase. mdh, an energy-supplying enzyme, catalyzes the interconversion of malate and oxaloacetate and plays crucial roles in several metabolic pathways including the citric acid cycle. the phosphorylation site wa ...201525860441
[pott's disease and immunological diagnosis of tuberculosis, about a pediatric clinical case].tuberculosis (tb) remains a major health problem in the world. the clinical forms of tb in children are variable, pulmonary involvement occurs in two thirds of cases. in the remaining third, clinical forms incluye node, meningeal and osteoarticular involvement.201525860054
applying spatiotemporal models to study risk of smear-positive tuberculosis in iran, 2001-2012.assessing tuberculosis (tb) distribution in regions over time is essential for health officials to have a proper understanding of current status, determine high-risk areas, and improve case management and resource allocation.201525860004
mycobacterium tuberculosis genotypic drug resistance patterns and clustering in jayapura, papua, indonesia.little is known about drug-resistant tuberculosis (tb) and its transmission in papua, which has one of the highest rates of tb in indonesia.201525859998
phenotypic and genotypic diversity in a multinational sample of drug-resistant mycobacterium tuberculosis isolates.to develop and evaluate rapid, molecular-based drug susceptibility testing (dst) for extensively drug-resistant tuberculosis (xdr-tb), we assembled a phenotypically and genotypically diverse collection of mycobacterium tuberculosis isolates from patients evaluated for drug resistance in four high-burden countries.201525859997
diverging biological roles among human monocyte subsets in the context of tuberculosis infection.circulating monocytes (mo) play an essential role in the host immune response to chronic infections. we previously demonstrated that cd16(pos) mo were expanded in tb (tuberculosis) patients, correlated with disease severity and were refractory to dendritic cell differentiation. in the present study, we investigated whether human mo subsets (cd16(neg) and cd16(pos)) differed in their ability to influence the early inflammatory response against mycobacterium tuberculosis. we first evaluated the ca ...201525858460
tuberculosis in late neolithic-early copper age human skeletal remains from hungary.alsónyék-bátaszék in southern hungary is one of the largest late neolithic settlements and cemeteries excavated in central europe. in total, 2359 burials from the late neolithic - early copper age lengyel culture were found between 2006 and 2009 [1]. anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of pott's disease dated to the early 5(th) millennium bc. in this study, selected specimen ...201525857937
the early mediaeval manorial estate of gars/thunau, lower austria: an enclave of endemic tuberculosis?in recent decades, an increasing number of studies have aimed to shed light on the origin and spread of tuberculosis in past human populations. here we present the results of a systematic palaeodemographic and palaeopathological survey of the early mediaeval population of gars/thunau (lower austria), which - at this stage - includes 373 individuals recovered at two archaeological sub-sites: a fortified settlement (including a necropolis) at the top of a hill - probably reserved for social and mi ...201525857936
toll-like receptor 1 variations influence susceptibility and immune response to mycobacterium tuberculosis.tuberculosis (tb), a disease caused by mycobacterium tuberculosis (mtb) infection, is still a global public health problem. tb susceptibility varies greatly in infected individuals, and mycobacterial recognition by the innate immune system likely affects disease course and outcome. this research describes a single nucleotide polymorphism in the toll-like receptor (tlr) 1 gene that functionally alters the innate immune response to mtb and is associated with tb susceptibility in india.201525857934
genetic polymorphisms in the toll-like receptor 10, interleukin (il)17a and il17f genes differently affect the risk for tuberculosis in croatian population.proinflammatory conditions leading to activation of macrophages via interferon-γ bear an important role in host defence against intracellular bacteria such as mycobacterium tuberculosis (mt). interleukin-17 plays a similar role, as it appears to be also an activator of macrophages. recently, the tlr-10 was identified as an anti-inflammatory factor that exerts its action via association with the tlr-2 chain at the cell surface of macrophages, the latter being an mt-binding protein. we have previo ...201525857634
isolation of mycobacterium tuberculosis from sputum of tribal, non-tribal pulmonary tuberculosis patients of andaman & nicobar islands by conventional culture method and assessment of first line anti-tuberculosis drug susceptibility patterns.drug resistance surveys have not yet conducted in these islands and as such no data exists on drug resistance currently.201525857562
detection of drug resistance in mycobacterium tuberculosis: methods, principles and applications.the growing emergence of multidrug resistant tuberculosis (mdr-tb) strains is obstructing efforts for the control and management of tb. proper management of mdr-tb relies on early recognition of drug resistance followed by timely treatment initiation. several diagnostic methods, both phenotypic and molecular, have been developed in last few years for rapid identification of drug resistant (dr)-tb. revised national tuberculosis control programmes (rntps) may find it tough to choose from the puzzl ...201525857561
mycobacterium tuberculosis biofilm - a new perspective. 201525857559
comparative proteomic analysis of sequential isolates of mycobacterium tuberculosis from a patient with pulmonary tuberculosis turning from drug sensitive to multidrug resistant.tuberculosis is a major health problem in india, and the emergence of multidrug resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis (mtb) has further complicated the situation. though several studies characterizing drug sensitive and drug resistant strains are available in literature, almost all studies are done on unrelated strains. therefore, the objective of this study was to compare the proteomic data of four sequential isolates of mtb from a single pat ...201525857493
proteomics of multidrug resistant mycobacterium tuberculosis clinical isolates: a peep show on mechanism of drug resistance & perhaps more. 201525857490
could inducible protein-10 and heparin-binding hemagglutinin improve the detection of mycobacterium tuberculosis-infected subjects in a country with low incidence of tuberculosis?this study aimed to evaluate inducible protein-10 (ip-10) as a biomarker besides interferon-gamma (ifn-γ) to improve the identification of active tuberculosis (tb) and latent tubercular infection (ltbi) in a country with a low incidence of tb.201525856090
prevalence of drug resistant mycobacterium tuberculosis among children in china.the available data on the epidemic of drug resistant tuberculosis (tb) among children in china is limited. this study attempted to clarify the drug resistance profiles of clinical strains isolated from children and estimate risk factors related to acquisition of drug resistance. all mycobacterium tuberculosis strains from children (age <15 years) and adolescent (age 15-18 years) tb patients received in the strain library of chinese center for disease control and prevention between january 2005 a ...201525814302
tuberculosis and survival in past populations: a paleo-epidemiological appraisal.historical assessments of the last two centuries consistently placed tuberculosis as the leading cause of mortality. however, for earlier periods, we can only calculate the frequencies of archaeological bone lesions, which tell us little about the real impact of the disease on mortality. these lesions are usually observed in individuals who have developed immune resistance, which is visible as healed osteo-articular lesions. this study aimed to test the differential impacts of tuberculosis, crib ...201525814301
two positive tuberculosis cases in the late nigrovits family, 18th century, vác, hungary.two mummies of the hungarian mummy collection from vác were the subjects of anthropological, paleopathological, radiological, paleomicrobiological, paleohistological and paleoproteomic studies. both individuals belonged to the same family. the father, józsef nigrovits (no 29), died at the age of 55 on the 11th of november 1793; his son, antal nigrovits (no 54), died on the 16th of july 1803, at the age of 22. they lived in the 18th century in vác, a small town in northern hungary. the macroscopi ...201525814300
label-free quantitative proteomics reveals a role for the mycobacterium tuberculosis seca2 pathway in exporting solute binding proteins and mce transporters to the cell wall.mycobacterium tuberculosis is an example of a bacterial pathogen with a specialized seca2-dependent protein export system that contributes to its virulence. our understanding of the mechanistic basis of seca2-dependent export and the role(s) of the seca2 pathway in m. tuberculosis pathogenesis has been hindered by our limited knowledge of the proteins exported by the pathway. here, we set out to identify m. tuberculosis proteins that use the seca2 pathway for their export from the bacterial cyto ...201525813378
antitubercular nanocarrier combination therapy: formulation strategies and in vitro efficacy for rifampicin and sq641.tuberculosis (tb) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. to reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (ncs) were prepared and evaluated for efficacy in vitro in mycobacterium tuberculosis-infected macrophages. rifampicin (rif), a current, broad-spectrum antibiotic us ...201525811733
a microbiological revolution meets an ancient disease: improving the management of tuberculosis with genomics.tuberculosis (tb) is an ancient disease with an enormous global impact. despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of tb require significant clinical microbiology laboratory resources. current methods for the detection and characterization of mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. since the sequencing of the first m. ...201525810419
predominant mycobacterium tuberculosis families and high rates of recent transmission among new cases are not associated with primary multidrug resistance in lima, peru.sputum samples from new tuberculosis (tb) cases were collected over 2 years as part of a prospective study in the northeastern part of lima, peru. to measure the contribution of recent transmission to the high rates of multidrug resistance (mdr) in this area, mycobacterium tuberculosis complex (mtbc) isolates were tested for drug susceptibility to first-line drugs and were genotyped by spoligotyping and 15-locus mycobacterial interspersed repetitive-unit (miru-15)-variable-number tandem repeat ( ...201525809979
the complex evolution of antibiotic resistance in mycobacterium tuberculosis.multidrug-resistant and extensively drug-resistant tuberculosis (tb) represent a major threat to the control of the disease worldwide. the mechanisms and pathways that result in the emergence and subsequent fixation of resistant strains of mycobacterium tuberculosis are not fully understood and recent studies suggest that they are much more complex than initially thought. in this review, we highlight the exciting new areas of research within tb resistance that are beginning to fill these gaps in ...201525809763
understanding anti-tuberculosis drug efficacy: rethinking bacterial populations and how we model them.tuberculosis still remains a global health emergency, claiming 1.5 million lives in 2013. the bacterium responsible for this disease, mycobacterium tuberculosis (m.tb), has successfully survived within hostile host environments, adapting to immune defence mechanisms, for centuries. this has resulted in a disease that is challenging to treat, requiring lengthy chemotherapy with multi-drug regimens. one explanation for this difficulty in eliminating m.tb bacilli in vivo is the disparate action of ...201525809760
repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis.tuberculosis (tb) remains a serious concern more than two decades on from when the world health organization declared it a global health emergency. the alarming rise of antibiotic resistance in mycobacterium tuberculosis, the etiological agent of tb, has made it exceedingly difficult to control the disease with the existing portfolio of anti-tb chemotherapy. the development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. the develop ...201525809756
frequency of mycobacterium tuberculosis-specific cd8+ t-cells in the course of anti-tuberculosis treatment.anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific t-cells. in order to objectively gauge mycobacterium tuberculosis (mtb)-specific cd8+ t-cells at the single-cell level, we developed soluble major histocompatibility complex (mhc) class i multimers/peptide multimers, which allow analysis of antigen-specific t-cells without ex vivo manipulation or functional tests. we constructed 38 mhc class i multimers covering some of the m ...201525809751
mycobacterium tuberculosis-specific and mhc class i-restricted cd8+ t-cells exhibit a stem cell precursor-like phenotype in patients with active pulmonary tuberculosis.the nature and longevity of the t-cell response directed against mycobacterium tuberculosis (mtb) are important for effective pathogen containment. we analyzed ex vivo the nature of mtb antigen-specific t-cell responses directed against the mtb secreted antigens rv0288, rv1886c, rv3875, the antigens rv2958c, rv2957, and rv0447c (intracellular, non-secreted enzymes) in blood from korean patients with active tuberculosis (tb). mtb-specific t-cell function was defined by intracellular cytokine prod ...201525809750
epidemiologic link between tuberculosis and cigarette/biomass smoke exposure: limitations despite the vast literature.the geographic overlap between the prevalence of cigarette smoke (cs) exposure and tuberculosis (tb) in the world is striking. in recent years, relatively large number of studies has linked cigarette or biomass fuel smoke exposure and various aspects of tb. our goals are to summarize the significance of the known published studies, graphically represent reports that quantified the association and discuss their potential limitations. pubmed searches were performed using the key words 'tuberculosi ...201525808744
a novel pathway producing dimethylsulphide in bacteria is widespread in soil environments.the volatile compound dimethylsulphide (dms) is important in climate regulation, the sulphur cycle and signalling to higher organisms. microbial catabolism of the marine osmolyte dimethylsulphoniopropionate (dmsp) is thought to be the major biological process generating dms. here we report the discovery and characterization of the first gene for dmsp-independent dms production in any bacterium. this gene, mdda, encodes a methyltransferase that methylates methanethiol and generates dms. mdda func ...201525807229
crystal structures of the kinase domain of the sulfate-activating complex in mycobacterium tuberculosis.in mycobacterium tuberculosis the sulfate activating complex provides a key branching point in sulfate assimilation. the complex consists of two polypeptide chains, cysd and cysn. cysd is an atp sulfurylase that, with the energy provided by the gtpase activity of cysn, forms adenosine-5'-phosphosulfate (aps) which can then enter the reductive branch of sulfate assimilation leading to the biosynthesis of cysteine. the cysn polypeptide chain also contains an aps kinase domain (cysc) that phosphory ...201525807013
using a label free quantitative proteomics approach to identify changes in protein abundance in multidrug-resistant mycobacterium tuberculosis.reports in recent years indicate that the increasing emergence of resistance to drugs be using to tb treatment. the resistance to them severely affects to options for effective treatment. the emergence of multidrug-resistant tuberculosis has increased interest in understanding the mechanism of drug resistance in m. tuberculosis and the development of new therapeutics, diagnostics and vaccines. in this study, a label-free quantitative proteomics approach has been used to analyze proteome of multi ...201525805910
prophylactic potential of defensins and l-isoleucine in tuberculosis household contacts: an experimental model.patients with pulmonary tuberculosis (tb) are the most important source for tb infection, being the risk of infection determined by the source case infectiousness and the contact closeness. currently, the administration of isoniazid is used to prevent the infection to some extent in household contacts. at experimental level, defensins are efficient molecules for the treatment of tb and other infectious diseases.201525804474
human cd8+ t-cells recognizing peptides from mycobacterium tuberculosis (mtb) presented by hla-e have an unorthodox th2-like, multifunctional, mtb inhibitory phenotype and represent a novel human t-cell subset.mycobacterial antigens are not exclusively presented to t-cells by classical hla-class ia and hla-class ii molecules, but also through alternative antigen presentation molecules such as cd1a/b/c, mr1 and hla-e. we recently described mycobacterial peptides that are presented in hla-e and recognized by cd8+ t-cells. using t-cell cloning, phenotyping, microbiological, functional and rna-expression analyses, we report here that these t-cells can exert cytolytic or suppressive functions, inhibit myco ...201525803478
antimycobacterial and cytotoxicity activity of microcystins.the present work aimed to evaluate the antimycobacterial activity and cytotoxicity of microcystis aeruginosa toxins, the mc-lr variant and purified extract of [d-leu(1)] microcystin-lr.201525802510
mycobacterium tuberculosis-specific cd4 t cells are the principal source of ifn-γ in quantiferon assays in healthy persons. 201525802032
old world tuberculosis: evidence from human remains with a review of current research and future prospects.the evidence for tb in archaeological human remains for the old world is reviewed in published and some unpublished sources. the evidence of pott's disease was considered specific for tb, with other bone changes, such as rib lesions, as non-specific. limitations of the data are discussed. most evidence for tb comes from skeletons from the northern hemisphere, particularly in europe in the late medieval period (12(th)-16th centuries ad), but there is early evidence in the near/middle east and egy ...201525802030
mycobacterium tuberculosis infection of the 'non-classical immune cell'.mycobacterium tuberculosis can infect 'non-classical immune cells', which comprise a significant constituency of cells that reside outside of those defined as 'classical immune cells' from myeloid or lymphoid origin. here we address the influence of specific 'non-classical immune cells' in host responses and their effects in controlling mycobacterial growth or enabling an environment conducive for bacilli persistence. the interaction of m. tuberculosis with epithelial cells, endothelial cells, f ...201525801479
lead selection and characterization of antitubercular compounds using the nested chemical library.discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. to find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. we screened more than 17,000 compounds from vichem's nested chemical library™ using an integrated strategy involving whole cell-based assays with corynebacterium g ...201525801335
genetic mutations associated with isoniazid resistance in mycobacterium tuberculosis: a systematic review.tuberculosis (tb) incidence and mortality are declining worldwide; however, poor detection of drug-resistant disease threatens to reverse current progress toward global tb control. multiple, rapid molecular diagnostic tests have recently been developed to detect genetic mutations in mycobacterium tuberculosis (mtb) genes known to confer first-line drug resistance. their utility, though, depends on the frequency and distribution of the resistance associated mutations in the pathogen population. m ...201525799046
air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity.inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (tb). whether exposure to ambient air pollution particulate matter (pm) alters protective human host immune responses against mycobacterium tuberculosis has been little studied. here, we examined the effect of pm from iztapalapa, a municipality of mexico city, with aerodynamic diameters below 2.5 μm (pm2.5) and 10 μm (pm10) on innate antimycobacterial immune responses in human alveolar ...201525847963
genotypic diversity of multidrug-, quinolone- and extensively drug-resistant mycobacterium tuberculosis isolates in thailand.drug-resistant tuberculosis (tb), which includes multidrug-resistant (mdr-tb), quinolone-resistant (qr-tb) and extensively drug-resistant tuberculosis (xdr-tb), is a serious threat to tb control. we aimed to characterize the genotypic diversity of drug-resistant tb clinical isolates collected in thailand to establish whether the emergence of drug-resistant tb is attributable to transmitted resistance or acquired resistance. we constructed the first molecular phylogeny of mdr-tb (n=95), qr-tb (n= ...201525847698
microrna-155 knockout mice are susceptible to mycobacterium tuberculosis infection.micrornas (mirnas) are short, conserved, non-coding rna molecules that repress translation, followed by the decay of mirna-targeted mrnas that encode molecules involved in cell differentiation, development, immunity and apoptosis. at least six mirnas, including microrna-155 (mir-155), were up-regulated when born marrow-derived macrophages from c57bl/6 mice were infected with mycobacterium tuberculosis erdman. c57bl/6 mice intravenously infected with erdman showed up-regulation of mir-155 in live ...201525846955
drug resistance in mycobacterium tuberculosis: molecular mechanisms challenging fluoroquinolones and pyrazinamide effectiveness.physicians are more and more often challenged by difficult-to-treat cases of tb. they include patients infected by strains of mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin (multidrug-resistant tb) or to at least one fluoroquinolone (fq) and one injectable, second-line anti-tb drug in addition to isoniazid and rifampicin (extensively drug-resistant tb). the drug treatment of these cases is very long, toxic, and expensive, and, unfortunately, the proportion of ...201525846529
performance of genotype mtbdrplus in the detection of resistance to rifampicin and isoniazid among clinical mycobacteria isolates in ilorin, nigeria.performance of genotype mtbdrplus assay against lowenstein jensen (lj) proportion method of drug susceptibility testing (dst) in detection of resistance among clinical mycobacteria isolates to rifampicin (rmp) and isoniazid (inh) was evaluated in ilorin, nigeria.201525845392
prime-boost vaccination strategy with bacillus calmette-guérin (bcg) and liposomized alpha-crystalline protein 1 reinvigorates bcg potency.bacillus calmette-guérin (bcg) remains the only available and most widely administered vaccine against mycobacterium tuberculosis (mtb), yet it fails to protect vaccinated individuals either from primary infection or reactivation of latent tuberculosis (tb). despite bcg's variable efficacy against tb, the fact remains that bcg imparts protection in children against the disease, indicating that bcg possesses a wide protective antigenic repertoire. however, its failure to impart protection in adul ...201525845290
transcriptional profile of mycobacterium tuberculosis replicating in type ii alveolar epithelial cells.mycobacterium tuberculosis (m. tb) infection is initiated by the few bacilli inhaled into the alveolus. studies in lungs of aerosol-infected mice provided evidence for extensive replication of m. tb in non-migrating, non-antigen-presenting cells in the alveoli during the first 2-3 weeks post-infection. alveoli are lined by type ii and type i alveolar epithelial cells (aec) which outnumber alveolar macrophages by several hundred-fold. m. tb dna and viable m. tb have been demonstrated in aec and o ...201525844539
the internal gene duplication and interrupted coding sequences in the mmpl genes of mycobacterium tuberculosis: towards understanding the multidrug transport in an evolutionary perspective.the multidrug resistance has emerged as a major problem in the treatment of many of the infectious diseases. tuberculosis (tb) is one of such disease caused by mycobacterium tuberculosis. there is short term chemotherapy to treat the infection, but the main hurdle is the development of the resistance to antibiotics. this resistance is primarily due to the impermeable mycolic acid rich cell wall of the bacteria and other factors such as efflux of antibiotics from the bacterial cell. the mmpl (myc ...201525841626
genetic diversity of the mycobacterium tuberculosis beijing family in brazil and mozambique and relation with infectivity and induction of necrosis in thp-1 cells.the success of the mycobacterium tuberculosis beijing (mtbb) lineage in different geographical regions has been attributed to high transmission, increased virulence, drug resistance and rapid adaptation to the host. in some countries of secondary mtbb dispersion like south africa and peru, rising prevalence of the beijing strains is registered. however, in neighboring countries to affected regions such as mozambique and brazil, respectively, the prevalence of these strains is still low and this ...201525841343
human and tuberculosis co-evolution: an integrative view.tuberculosis (tb) ranks as the second cause of death from an infectious disease worldwide after hiv. archaeogenetics and evolutionary scenario for the mycobacterium tuberculosis complex (mtbc) are in favor of a long-term interaction between tuberculosis and humans, predating the neolithic period, contrary to the traditional belief. if tuberculosis evolved as a human pathogen in africa and has spread outside africa about more than ten-thousand years ago, its life history traits have been shaped b ...201525841342
a multiplex pcr method for detection of aspergillus spp. and mycobacterium tuberculosis in bal specimens.the aim of this study was the detection of aspergillus species and mycobacterium tuberculosis together in bronchoalveolar lavage (bal) using of multiplex pcr.201525840850
unusual spinal tuberculosis in an avar age skeleton (csongrád-felgyő, ürmös-tanya, hungary): a morphological and biomolecular study.the paleopathological analysis of a well-preserved young adult female skeleton from the ad 7-8th century (avar age) in hungary revealed multiple lytic lesions in all of the thoracic and lumbar vertebral bodies. the lesions were characterized by smooth marginal zones and space-occupying mass appearance. the considerable loss of spongy bone in the thoracolumbar vertebrae resulted in angular deformity and fusion, characteristic of the healing stage of tb. osteolytic lesions were also observed on th ...201525840822
Displaying items 47701 - 47800 of 53400