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alveolar epithelial cells in mycobacterium tuberculosis infection: active players or innocent bystanders?tuberculosis (tb) is a disease that kills one person every 18 s. tb remains a global threat due to the emergence of drug-resistant mycobacterium tuberculosis (m.tb) strains and the lack of an efficient vaccine. the ability of m.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells dur ...201626384325
mycobacterium tuberculosis: ecology and evolution of a human bacterium.some species of the mycobacterium tuberculosis complex (mtbc), particularly mycobacterium tuberculosis, which causes human tuberculosis (tb), are the first cause of death linked to a single pathogen worldwide. in the last decades, evolutionary studies have much improved our knowledge on mtbc history and have highlighted its long co-evolution with humans. its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (one-third of the entire human population), the d ...201526385049
assessment of the probability of introducing mycobacterium tuberculosis into danish cattle herds.tuberculosis is a zoonosis caused by mycobacterium spp. international trade in cattle is regulated with respect to mycobacterium bovis (m. bovis) but not mycobacterium tuberculosis (m. tuberculosis), despite that cattle can become infected with both species. in this study we estimated the annual probability (pintro) of introducing m. tuberculosis into the danish cattle population, by the import of cattle and/or by immigrants working in danish cattle herds. data from 2013 with date, number, and o ...201526385106
anti-tubercular drug development: computational strategies to identify potential compounds.inha is an attractive target to combat tuberculosis (tb), which is targeted by many pro-drugs (isoniazid, etc.) and drugs such as triclosan. however, triclosan is less useful as an antitubercular drug due to its low bioavailability and therefore, in order to overcome this difficulty, many derivatives of triclosan were prepared. here, we have combined various computational techniques to virtually screen out four potential triclosan derivatives. molecular docking methods have been employed to scre ...201526386453
in vitro antituberculosis activity of diterpenoids from the vietnamese medicinal plant croton tonkinensis.diterpenoids from the vietnamese medicinal plant croton tonkinensis are rich in ent-kaurane, kaurane and the grayanane class and are valuable intermediate plant metabolites with different bioactivities. in this study, we report the antituberculosis activity of these diterpenoids against both susceptible and resistant strains of m. tuberculosis for the first time. all of the ent-kaurane, kaurane and grayanane diterpenoids showed high to moderate activity against mycobacterium. the highest antitub ...201626386972
nr1d1 ameliorates mycobacterium tuberculosis clearance through regulation of autophagy.nr1d1 (nuclear receptor subfamily 1, group d, member 1), an adopted orphan nuclear receptor, is widely known to orchestrate the expression of genes involved in various biological processes such as adipogenesis, skeletal muscle differentiation, and lipid and glucose metabolism. emerging evidence suggests that various members of the nuclear receptor superfamily perform a decisive role in the modulation of autophagy. recently, nr1d1 has been implicated in augmenting the antimycobacterial properties ...201526390081
the essential role of cholesterol metabolism in the intracellular survival of mycobacterium leprae is not coupled to central carbon metabolism and energy production.mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and schwann cells. cholesterol is among the lipids with increased abundance in m. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. the present study investigated the capacity of m. leprae to acquire and metabolize cholesterol. in silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), th ...201526391209
raman spectroscopic monitoring of the growth of pigmented and non-pigmented mycobacteria.raman microspectroscopy has increased in popularity in the field of microbiology because it allows a spectral fingerprinting of bacterial pathogens at an unrivaled speed, which is important for the early treatment of infectious diseases such as tuberculosis. an indispensable prerequisite for the success of this method is a profound knowledge, how the spectral profiles depend on the age of the bacteria. we therefore followed the growth of two rapidly growing mycobacterium tuberculosis relatives, ...201526391403
the role of laboratory investigations in evaluating abdominal tuberculosis.tuberculosis (tb) continues to be a major health problem in developing countries like india. abdominal tb is defined as an infection of the peritoneum, or hollow or solid abdominal organs with mycobacterium tuberculosis (mtb). the gastrointestinal tract is one of the most frequent sites of extrapulmonary involvement in tb. the present study was undertaken to evaluate the role of laboratory investigations in the diagnosis of abdominal tb.201726392795
characteristics and outcomes of tuberculosis patients who fail to smear convert at two months in sri lanka.five districts in sri lanka.201326392992
a four-year nationwide molecular epidemiological study in estonia: risk factors for tuberculosis transmission.estonia has a high proportion of multidrug-resistant tuberculosis (mdr-tb). it is important to link molecular and epidemiological data to understand tb transmission patterns.201426393096
cough aerosol cultures of mycobacterium tuberculosis: insights on tst / igra discordance and transmission dynamics.the diagnosis of latent tuberculosis (tb) infection (ltbi) is complicated by the absence of a gold standard. discordance between tuberculin skin tests (tst) and interferon gamma release assays (igra) occurs in 10-20% of individuals, but the underlying mechanisms are poorly understood.201526394149
determination of in vitro synergy between linezolid and other antimicrobial agents against mycobacterium tuberculosis isolates.in this study, our objective was to explore the potential in vitro synergy between linezolid (lzd) and six other anti-tb drugs in mycobacterium tuberculosis strains, especially multidrug-resistant tuberculosis (mdr-tb) strains. among the different combinations, the lzd-clarithromycin (cla) combination showed the best synergism, which was observed in 85% (34/40) of 40 isolates. in addition, one (2.5%) and twenty-one (52.5%) of 40 isolates showed synergism for the lzd-levofloxcin (lev) and lzd-mox ...201526395151
structural basis for the regulation of the mmpl transporters of mycobacterium tuberculosis.the mycobacterial cell wall is critical to the virulence of these pathogens. recent work shows that the mmpl (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. the expression of the mycobacterium tuberculosis mmpl proteins is controlled by a complex regulatory network, including the tetr family transcriptional regulators rv3249c and rv1816. here we report the crystal structures of the ...201526396194
core component eccb1 of the mycobacterium tuberculosis type vii secretion system is a periplasmic atpase.pathogenic mycobacteria transport virulence factors across their complex cell wall via a type vii secretion system (t7ss)/early secreted antigenic target-6 of kda secretion system (esx). esx conserved component (ecc) b, a core component of the t7ss architecture, is predicted to be a membrane bound protein, but little is known about its structure and function. here, we characterize eccb1, showing that it is an atpase with no sequence or structural homology to other atpases located in the cell env ...201526396239
molecular epidemiology of mycobacterium tuberculosis isolates in 100 patients with tuberculosis using pulsed field gel electrophoresis.tuberculosis (tb) is a widespread infectious disease. today, tb has created a public health crisis in the world. genotyping of mycobacterium tuberculosis isolates is useful for surveying the dynamics of tb infection, identifying new outbreaks, and preventing the disease. different molecular methods for clustering of m. tuberculosis isolates have been used.201526396714
glpx gene in mycobacterium tuberculosis is required for in vitro gluconeogenic growth and in vivo survival.several enzymes involved in central carbon metabolism and gluconeogenesis play a critical role in survival and pathogenesis of mycobacterium tuberculosis (mtb). the only known functional fructose 1,6-bisphosphatase (fbpase) in mtb is encoded by the glpx gene and belongs to the class ii sub-family of fbpase. we describe herein the generation of a δglpx strain using homologous recombination. although the growth profile of δglpx is comparable to that of wild type mtb when grown on the standard enri ...201526397812
identification and characterization of lipase activity and immunogenicity of lipl from mycobacterium tuberculosis.lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. in this study, we expressed 10 members of the lip family of mycobacterium tuberculosis. among the 10 proteins, lipl displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. the optimal temperature for the lipase activity of lipl was demonstrated to be 37°c, and the optimal ph was 8.0. the lipase active center was not t ...201526398213
high-dose vitamin d3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.tuberculosis, including multidrug-resistant tuberculosis (mdr-tb), is a major global health problem. individuals with tuberculosis disease commonly exhibit vitamin d deficiency, which may adversely affect immunity and the response to therapy.201526399865
quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against mycobacterium tuberculosis and mycobacterium bovis.essential oils and their constituents are commonly known for their antibacterial, antifungal and antiparasitic activity, and there are also reports on the antimycobacterial properties, but more experimental data are needed for the description of the mechanism of action or structural (and molecular) properties related to the antimicrobial activity.201526400221
countrywide roll-out of xpert(®) mtb/rif in swaziland: the first three years of implementation.all 19 public health laboratories in swaziland that had xpert(®) mtb/rif machines installed as part of a countrywide roll-out between june 2011 and june 2014.201526400386
case report of a false positive result of the xpert(®) mtb/rif assay for rifampicin resistance in mycobacterium tuberculosis complex.in the present case, we report a false positive result for the detection of rifampicin (rif) resistance by the xpert(®) mtb/rif assay, version g4.miliary mycobacterium tuberculosis infection (miliary tb) was suspected in a 50-year old angolan woman. imaging of the thorax and abdomen displayed diffuse lesions. the xpert(®) mtb/rif assay conducted on the broncho-alveolar lavage (bal) fluid was positive for tb and positive for rif resistance. confirmatory molecular tests and the phenotypic drug sus ...201626400761
multidrug-resistant mycobacterium tuberculosis of the latin american mediterranean lineage, wrongly identified as mycobacterium pinnipedii (spoligotype international type 863 [sit863]), causing active tuberculosis in south brazil.we recently detected the spoligotype patterns of strains of mycobacterium pinnipedii, a species of the mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in porto alegre, south brazil. because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (miru-vntr) typing, verificatio ...201526400784
evaluation of the implementation of the xpert® mtb/rif assay in fiji.all xpert® mtb/rif tests performed in the three tb (tuberculosis) treatment centres in fiji from june 2012 to february 2013.201426400807
tuberculosis diagnostics in fiji: how reliable is culture?acid-fast bacilli (afb) smear microscopy and mycobacterium tuberculosis culture are the first-line diagnostic tests for tuberculosis (tb). the contamination of tb cultures significantly reduces the reliability of tb diagnosis.201426400808
vitamin d deficiency and tb disease phenotype.extrapulmonary tb is increasingly common, yet the determinants of the wide clinical spectrum of tb are poorly understood.201526400877
[participation of heat shock proteins in modulation of nf-кb transcription factor activation during bacterial infections].nuclear factor kappa-light-chain enhancer of activated b-cells (nf-кb) is a pleiotropic transcription factor, which regulates processes of immune response and inflammation. nf-кb can undergo activation as a result of bacterial infections via toll-like receptors (tlr), which recognize pathogen-associated molecular patterns (pamp), such as lipopolysaccharides (lps). stimulation of the cells results in phosphorylation of inhibitor кb (iкb) and the translocation of nf-кb to the nucleus, where the tr ...201526400883
structure of lpg0406, a carboxymuconolactone decarboxylase family protein possibly involved in antioxidative response from legionella pneumophila.lpg0406, a hypothetical protein from legionella pneumophila, belongs to carboxymuconolactone decarboxylase (cmd) family. we determined the crystal structure of lpg0406 both in its apo and reduced form. the structures reveal that lpg0406 forms a hexamer and have disulfide exchange properties. the protein has an all-helical fold with a conserved thioredoxin-like active site cxxc motif and a proton relay system similar to that of alkylhydroperoxidase from mycobacterium tuberculosis (mtahpd), sugges ...201526402328
perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria.perforin-2 (mpeg1) is a pore-forming, antibacterial protein with broad-spectrum activity. perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. in vitro, perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant staphylococcus aureus (mrsa) or salmonella typhimurium and perish shortly after epicutane ...201526402460
the xpert® mtb/rif assay in routine diagnosis of pulmonary tuberculosis: a multicentre study in lithuania.drug-resistant tuberculosis (tb) is an important public health problem in lithuania with mdr rates in new cases reaching 11% in 2012. currently available diagnostic tools are not fully adequate for an accurate and rapid result for diagnosis of tb and mdr-tb.201526403251
modulation of host ubiquitin system genes in human endometrial cell line infected with mycobacterium tuberculosis.endometrium is one of the most commonly affected sites in genital tuberculosis. the understanding of its interaction with the tubercle bacilli is of paramount importance for studying the pathogenesis of this disease. the main objective of this work was to study the interplay between mycobacterium tuberculosis and host endometrial epithelial cell lines (ishikawa cell lines), and to identify the differentially expressed genes upon tuberculosis infection. to study this, suppression subtractive hybr ...201626403675
management of latent mycobacterium tuberculosis infection: who guidelines for low tuberculosis burden countries.latent tuberculosis infection (ltbi) is characterised by the presence of immune responses to previously acquired mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (tb). here we report evidence-based guidelines from the world health organization for a public health approach to the management of ltbi in high risk individuals in countries with high or middle upper income and tb incidence of <100 per 100 000 per year. the guidelines strongly recommend systematic t ...201526405286
comparison of samples obtained from bronchoscopy of patients with and without bronchial anthracosis for investigating the prevalence of mycobacterium tuberculosis.bronchial anthracosis is caused by the deposition of carbon, silica or asbestos particles in mucosal and submucosal cells and macrophages, and it can lead to chronic bronchial obstruction. certain studies have reported an association between bronchial anthracosis and infection with mycobacterium tuberculosis. this study aimed to compare the samples obtained from bronchoscopy of patients with and without bronchial anthracosis for investigating the prevalence of mycobacterium tuberculosis.201526405675
identification of 13 blood-based gene expression signatures to accurately distinguish tuberculosis from other pulmonary diseases and healthy controls.tuberculosis (tb), caused by infection with mycobacterium tuberculosis, is still a major threat to human health worldwide. current diagnostic methods encounter some limitations, such as sample collection problem or unsatisfied sensitivity and specificity issue. moreover, it is hard to identify tb from some of other lung diseases without invasive biopsy. in this paper, the logistic models with three representative regularization approaches including lasso (the most popular regularization method), ...201526405955
development and evaluation of chitosan microparticles based dry powder inhalation formulations of rifampicin and rifabutin.the lung is the primary entry site and target for mycobacterium tuberculosis; more than 80% of the cases reported worldwide are of pulmonary tuberculosis. hence, direct delivery of anti-tubercular drugs to the lung would be beneficial in reducing both, the dose required, as well as the duration of therapy for pulmonary tuberculosis. in the present study, microsphere-based dry powder inhalation systems of the anti-tubercular drugs, rifampicin and rifabutin, were developed and evaluated, with a vi ...201626406162
experimental reactivation of pulmonary mycobacterium avium complex infection in a modified cornell-like murine model.the latency and reactivation of mycobacterium tuberculosis infection has been well studied. however, there have been few studies of the latency and reactivation of mycobacterium avium complex (mac), the most common etiological non-tuberculous mycobacterium species next to m. tuberculosis in humans worldwide. we hypothesized that latent mac infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. to ...201526406237
collaborative effort for a centralized worldwide tuberculosis relational sequencing data platform.continued progress in addressing challenges associated with detection and management of tuberculosis requires new diagnostic tools. these tools must be able to provide rapid and accurate information for detecting resistance to guide selection of the treatment regimen for each patient. to achieve this goal, globally representative genotypic, phenotypic, and clinical data are needed in a standardized and curated data platform. a global partnership of academic institutions, public health agencies, ...201526409275
the distribution of fitness costs of resistance-conferring mutations is a key determinant for the future burden of drug-resistant tuberculosis: a model-based analysis.drug resistance poses a serious challenge for the control of tuberculosis in many settings. it is well established that the expected future trend in resistance depends on the reproductive fitness of drug-resistant mycobacterium tuberculosis. however, the variability in fitness between strains with different resistance-conferring mutations has been largely ignored when making these predictions.201526409276
immune cell regulatory pathways unexplored as host-directed therapeutic targets for mycobacterium tuberculosis: an opportunity to apply precision medicine innovations to infectious diseases.the lack of novel antimicrobial drugs in development for tuberculosis treatment has provided an impetus for the discovery of adjunctive host-directed therapies (hdts). several promising hdt candidates are being evaluated, but major advancement of tuberculosis hdts will require understanding of the master or "core" cell signaling pathways that control intersecting immunologic and metabolic regulatory mechanisms, collectively described as "immunometabolism." core regulatory pathways conserved in a ...201526409283
t-cell therapy: options for infectious diseases.the emergence of drug-resistant tuberculosis is challenging tuberculosis control worldwide. in the absence of an effective vaccine to prevent primary infection with mycobacterium tuberculosis and tuberculosis disease, host-directed therapies may offer therapeutic options, particularly for patients with multidrug-resistant and extensively drug-resistant tuberculosis where prognosis is often limited. cd8(+) and cd4(+) t cells mediate antigen-specific adaptive cellular immune responses. their use i ...201526409284
b in tb: b cells as mediators of clinically relevant immune responses in tuberculosis.the protective role of b cells and humoral immune responses in tuberculosis infection has been regarded as inferior to cellular immunity directed to the intracellular pathogen mycobacterium tuberculosis. however, b-cell-mediated immune responses in tuberculosis have recently been revisited in the context of b-cell physiology and antigen presentation. we discuss in this review the diverse functions of b cells in tuberculosis, with a focus on their biological and clinical relevance to progression ...201526409285
translating the tuberculosis research agenda: much accomplished, but much more to be done.despite the availability of effective diagnostics and curative treatment regimens for tuberculosis, millions of people die each year of this disease. the steady global increase in the number of tuberculosis cases caused by multidrug-resistant and extensively drug-resistant strains of mycobacterium tuberculosis are of major concern, especially in light of the thin tuberculosis drug pipeline. new tuberculosis drugs are undergoing clinical evaluation, and renewed hope comes from fresh approaches to ...201526409286
validation of a homology model of mycobacterium tuberculosis dxs: rationalization of observed activities of thiamine derivatives as potent inhibitors of two orthologues of dxs.the enzyme dxs catalyzes the first, rate-limiting step of the 2-c-methyl-d-erythritol-4-phosphate (mep, 1) pathway using thiamine diphosphate (thdp) as cofactor; the dxs-catalyzed reaction constitutes also the first step in vitamin b1 and b6 metabolism in bacteria. dxs is the least studied among the enzymes of this pathway in terms of crystallographic information, with only one complete crystal structure deposited in the protein data bank (deinococcus radiodurans dxs, pdb: ). we synthesized a se ...201526411373
association of previous smoking habit and perceived social discrimination with the risk of multi-drug resistant tuberculosis in central nepal.multidrug-resistant tuberculosis (mdr tb) caused by mycobacterium tuberculosis resistant to both isoniazid and rifampicin with or without resistant to other drug, is among the most alarming pandemic problem. the objectives of this study was to assess the risk factors of mdr tb in central nepal.201526411721
dormancy models for mycobacterium tuberculosis: a minireview.dormancy models for mycobacterium tuberculosis play important roles in understanding various aspects of tuberculosis pathogenesis and in the testing of novel therapeutic regimens. by simulating the latent tuberculosis infection, in which the bacteria exist in a non-replicative state, the models demonstrate reduced susceptibility to antimycobacterial agents. this minireview outlines the models available for simulating latent tuberculosis both in vitro and in several animal species. additionally, ...201726413043
genotypic characteristics of mycobacterium tuberculosis circulating in xinjiang, china.tuberculosis (tb), a chronic infectious disease caused by mycobacterium tuberculosis (mtb), poses a serious threat to human health. we investigated the genotypes of mtb in the high prevalence province xinjiang, china.201626414438
phenothiazines as a solution for multidrug resistant tuberculosis: from the origin to present.historically, multiplicity of actions in synthetic compounds is a rule rather than exception. the science of non-antibiotics evolved in this background. from the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. the phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. the emergence of h ...201526415662
efficient calculation of enzyme reaction free energy profiles using a hybrid differential relaxation algorithm: application to mycobacterial zinc hydrolases.determination of the free energy profile for an enzyme reaction mechanism is of primordial relevance, paving the way for our understanding of the enzyme's catalytic power at the molecular level. although hybrid, mostly dft-based, qm/mm methods have been extensively applied to this type of studies, achieving accurate and statistically converged results at a moderate computational cost is still an open challenge. recently, we have shown that accurate results can be achieved in less computational t ...201526415840
moxifloxacin use and its association on the diagnosis of pulmonary tuberculosis in an inner city emergency department.moxifloxacin can be used in the treatment of tuberculosis, its effect on the diagnosis and treatment of pulmonary tuberculosis is not well characterized.201626416134
engagement of the aryl hydrocarbon receptor in mycobacterium tuberculosis-infected macrophages has pleiotropic effects on innate immune signaling.understanding the mechanisms of host macrophage responses to mycobacterium tuberculosis is essential for uncovering potential avenues of intervention to boost host resistance to infection. macrophage transcriptome profiling revealed that m. tuberculosis infection strongly induced the expression of several enzymes controlling tryptophan catabolism. these included ido1 and tryptophan 2,3-dioxygenase, which catalyze the rate-limiting step in the kynurenine pathway, producing ligands for the aryl hy ...201526416282
antigen-specific human nkt cells from tuberculosis patients produce il-21 to help b cells for the production of immunoglobulins.natural killer t (nkt) cells from mouse and human play an important role in the immune responses against mycobacterium tuberculosis. however, the function of cd3(+)tcrvβ11(+) nkt cells at the local site of m. tuberculosis infection remains poorly defined. in the present study, we found that after stimulation with m. tuberculosis antigens, nkt cells isolated from tuberculosis (tb) pleural fluid mononuclear cells (pfmcs) produced il-21 and other cytokines including ifn-γ, tnf-α, il-2 and il-17. il ...201526416419
evolution of mycolic acid biosynthesis genes and their regulation during starvation in mycobacterium tuberculosis.mycobacterium tuberculosis, the etiological agent of tuberculosis, is a gram-positive bacterium with a unique cell envelope composed of an essential outer membrane. mycolic acids, which are very-long-chain (up to c100) fatty acids, are the major components of this mycomembrane. the enzymatic pathways involved in the biosynthesis and transport of mycolates are fairly well documented and are the targets of the major antituberculous drugs. in contrast, only fragmented information is available on th ...201526416833
differential influence of nutrient-starved mycobacterium tuberculosis on adaptive immunity results in progressive tuberculosis disease and pathology.when infected with mycobacterium tuberculosis, most individuals will remain clinically healthy but latently infected. latent infection has been proposed to partially involve m. tuberculosis in a nonreplicating stage, which therefore represents an m. tuberculosis phenotype that the immune system most likely will encounter during latency. it is therefore relevant to examine how this particular nonreplicating form of m. tuberculosis interacts with the host immune system. to study this, we first ind ...201526416911
differences in antigen-specific cd4+ responses to opportunistic infections in hiv infection.hiv-infected individuals with severe immunodeficiency are at risk of opportunistic infection (oi). tuberculosis (tb) may occur without substantial immune suppression suggesting an early and sustained adverse impact of hiv on mycobacterium tuberculosis (mtb)-specific cell mediated immunity (cmi). this prospective observational cohort study aimed to observe differences in oi-specific and mtb-specific cmi that might underlie this. using polychromatic flow cytometry, we compared cd4+ responses to mt ...201526417433
novel epitopes identified from efflux pumps of mycobacterium tuberculosis could induce cytotoxic t lymphocyte response.overcoming drug-resistance is one of the major challenges to control tuberculosis (tb). the up-regulation of efflux pumps is one common mechanism that leads to drug-resistance. therefore, immunotherapy targeting these efflux pump antigens could be promising strategy to be combined with current chemotherapy. considering that cd8+ cytotoxic t lymphocytes (ctls) induced by antigenic peptides (epitopes) could elicit hla-restricted anti-tb immune response, efflux pumps from classical abc family (myco ...201526417538
mutations found in embcab, embr, and ubia genes of ethambutol-sensitive and -resistant mycobacterium tuberculosis clinical isolates from china.to better understand the molecular mechanisms of ethambutol (emb) resistance, the mutant hot spot region of five genes (embb, emba, embc, embr, and ubia) was amplified and sequenced in 109 emb-resistant and 153 emb-susceptible clinical isolates from china. twenty-seven emb-susceptible isolates were found to have nonsynonym mutations, 23 of which were in embb. the mutations occurred most frequently in embb (85.3%, 93) and were seldom in embc (2.8%, 3), emba (3.7%, 4), embr (3.7%, 4), and ubia (8. ...201526417605
phosphorylation of mycobacterium tuberculosis protein tyrosine kinase a ptka by ser/thr protein kinases.mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), has inflicted about one third of mankind and claims millions of deaths worldwide annually. signalling plays an important role in mtb pathogenesis and persistence, and thus represents attractive resource for drug target candidates. here, we show that protein tyrosine kinase a (ptka) can be phosphorylated by mtb endogenous eukaryotic-like ser/thr protein kinases (estpks). kinase assays showed that pkna, pknd, pknf, and pkn ...201526417687
multi-etiological nature of tuberculosis-like lesions in condemned pigs at the slaughterhouse.tuberculosis-like lesions (tbl) in pigs have been associated with microorganisms other than mycobacteria. in this work a histopathological and microbiological evaluation of tbl in pigs is shown. a total of 352 samples belonging to 171 pigs totally condemned at slaughterhouse due to generalized tbl were sampled and selected for analysis. pyogranulomatous (56.2%) and granulomatous lesions (20.2%) were observed in all analysed organs. most of the granulomas observed in both lymph nodes and lungs be ...201526418681
evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of mycobacterium tuberculosis isolates from kwazulu-natal.the continued advance of antibiotic resistance threatens the treatment and control of many infectious diseases. this is exemplified by the largest global outbreak of extensively drug-resistant (xdr) tuberculosis (tb) identified in tugela ferry, kwazulu-natal, south africa, in 2005 that continues today. it is unclear whether the emergence of xdr-tb in kwazulu-natal was due to recent inadequacies in tb control in conjunction with hiv or other factors. understanding the origins of drug resistance i ...201526418737
high frequency genetic transformation of cichorium intybus l. using nptii gene as a selective marker.cichorium intybus l. is an important vegetable crop used as salad (leaf form) and for the production of coffee substitutes (root form). at the same time these plants can also be used in biotechnologies for synthesis of pharmaceutical proteins. here we report the possibility of high frequency agrobacterium rhizogenes- or a. tumefaciens-mediated transformation of c. intybus l. for construction of transgenic "hairy" roots and plants. the used plasmids contained target human interferonifn-α2b gene, ...201526419064
noninvasive tuberculosis screening in free-living primate populations in gombe national park, tanzania.recent advances in noninvasive detection methods for mycobacterial infection in primates create new opportunities for exploring the epidemiology of tuberculosis in free-living species. chimpanzees (pan troglodytes schweinfurthii) and baboons (papio anubis) in gombe national park, tanzania, were screened for infection with pathogens of the mycobacterium tuberculosis complex using fecal is6110 pcr; none was positive. this study demonstrates the feasibility of large-scale mycobacterial screening in ...201626419483
recombinant expression of a functional myo-inositol-1-phosphate synthase (mips) in mycobacterium smegmatis.myo-inositol-1-phosphate synthase (mips, e.c. 5.5.1.4) catalyzes the first step in inositol production-the conversion of glucose-6-phosphate (glc-6p) to myo-inositol-1-phosphate. while the three dimensional structure of mips from mycobacterium tuberculosis has been solved, biochemical studies examining the in vitro activity have not been reported to date. herein we report the in vitro activity of mycobacterial mips expressed in e. coli and mycobacterium smegmatis. recombinant expression in e. co ...201526420670
profile of interferon-gamma response to latency-associated and novel in vivo expressed antigens in a cohort of subjects recently exposed to mycobacterium tuberculosis.recently some latency-associated antigens (laa) of mycobacterium tuberculosis were described, as rv2029c, rv2031c, rv2034, rv2628 and rv3353c. of which, the rv2034 and rv3353c also demonstrated in vivo expression. therefore evaluating the immune response to these antigens may help to understand their role in latent tb infection. in a 1-year longitudinal study, ifn-γ response by in vitro peripheral blood mononuclear cells stimulation with laa was investigated in subjects recently exposed to tb, c ...201526421415
[urinary tuberculosis: serious complications may occur when diagnosis is delayed].genitourinary tuberculosis is the third most common form of extrapulmonary tuberculosis, comprising 4 - 17% of extrapulmonary forms. the authors describe the case of a patient with recurrent urinary tract infections, without isolation of an infectious agent and without symptomatic resolution, despite antibiotic treatment. imaging exams showed left ureteral stenosis with moderate hydronephrosis. the attempt of retrograde catheterization was impossible so we opted for percutaneous nephrostomy to r ...201526421792
trends of mycobacterium bovis isolation and first-line anti-tuberculosis drug susceptibility profile: a fifteen-year laboratory-based surveillance.mycobacterium tuberculosis causes the majority of tuberculosis (tb) cases in humans; however, in developing countries, human tb caused by m. bovis may be frequent but undetected. human tb caused by m. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. we describe the trends of m. bovis isolation from human samples and first-line drug susceptibility during a ...201526421930
in vitro activity against mycobacterium tuberculosis of levofloxacin, moxifloxacin and ub-8902 in combination with clofazimine and pretomanid.multidrug resistance has become a problem in the management of tuberculosis, with an urgent need for research into new drugs as well as the development of efficacious drug combinations and regimens. the main objective of this study was to assess and compare the efficacy of three antituberculous combinations (clofazimine/pretomanid/levofloxacin, clofazimine/pretomanid/moxifloxacin and clofazimine/pretomanid/ub-8902) against multidrug-resistant (mdr) and drug-susceptible clinical isolates of mycob ...201526421981
synthesis and preliminary biological evaluation of a small library of hybrid compounds based on ugi isocyanide multicomponent reactions with a marine natural product scaffold.a mixture-based combinatorial library of five ugi adducts (4-8) incorporating known antitubercular and antimalarial pharmacophores was successfully synthesized, starting from the naturally occurring diisocyanide 3, via parallel ugi four-center three-component reactions (u-4c-3cr). the novel α-acylamino amides obtained were evaluated for their antiinfective potential against laboratory strains of mycobacterium tuberculosis h37rv and chloroquine-susceptible 3d7 plasmodium falciparum. interestingly ...201526421992
diagnosis of pulmonary and extrapulmonary tuberculosis based on detection of mycobacterial antigen 85b by immuno-pcr.we developed a novel indirect sandwich immuno-polymerase chain reaction (i-pcr) assay for the detection of mycobacterial antigen 85b (ag85b, 30kda, rv1886c) in pulmonary tuberculosis (ptb) and extrapulmonary tuberculosis (eptb) patients. the amino-modified reporter dna was covalently attached with the antidetection antibody through a heterobifunctional cross-linking agent succinimidyl 4-[n-maleimidomethyl]-cyclohexane-1-carboxylate. the detection limit of ag85b by i-pcr was found to be 1 femtogr ...201526422085
construction of a semisynthetic human vh single-domain antibody library and selection of domain antibodies against α-crystalline of mycobacterium tuberculosis.the use of human variable heavy (vh) domain antibodies has been on the rise due to their small scaffold size and simple folding mechanism. a highly diverse library is largely dependent on the diversity introduced within the complementarity-determining region (cdr) cassettes. here we introduced diversity with the use of a single framework diversifying all three cdrs using tailored codons consisting of degenerate trinucleotides (nnk). the length of the degeneracy in the cdrs was also taken into co ...201626423338
a single-centre experience of relaparoscopy in complications of laparoscopic inguinal hernia repair-feasibility and outcomes.management of complications of laparoscopic inguinal hernia repair remains challenging as well as debatable. relaparoscopy in management of these complications is relatively newer concept. we tried to analyse the feasibility of relaparoscopy (transabdominal preperitoneal approach) in management of complications of laparoscopic inguinal hernia repair.201626423411
a single-nucleotide-polymorphism real-time pcr assay for genotyping of mycobacterium tuberculosis complex in peri-urban kampala.accurate and high-throughput genotyping of mycobacterium tuberculosis complex (mtbc) may be important for understanding the epidemiology and pathogenesis of tuberculosis (tb). in this study, we report the development of a lightcycler® real-time pcr single-nucleotide-polymorphism (lrps) assay for the rapid determination of mtbc lineages/sublineages in minimally processed sputum samples from tb patients.201526423522
peritoneal tuberculosis presenting with portal vein thrombosis and transudative ascites - a diagnostic dilemma: case report.peritoneal tuberculosis is an important problem in regions of the world where tuberculosis is still prevalent (chest 1991; 99:1134). atypical presentations such as portal vein thrombosis can delay diagnosis or result in misdiagnosis (gut 1990; 31:1130, acta clinbelg 2012; 67(2):137-9, j cytol histol 2014; 5:278, digestive diseases and sciences 1991; 36(1):112-115). a high index of suspicion is required for the diagnosis of peritoneal tuberculosis, as the analysis of peritoneal fluid for tubercul ...201526423615
hiv-1 tuberculosis-associated immune reconstitution inflammatory syndrome.patients co-infected with hiv-1 and tuberculosis (tb) are at risk of developing tb-associated immune reconstitution inflammatory syndrome (tb-iris) following commencement of antiretroviral therapy (art). tb-iris is characterized by transient but severe localized or systemic inflammatory reactions against mycobacterium tuberculosis antigens. here, we review the risk factors and clinical management of tb-iris, as well as the roles played by different aspects of the immune response in contributing ...201626423994
screening and characterization of linear b-cell epitopes by biotinylated peptide libraries.identification of b-cell epitopes is important for the use of antibodies as therapeutic agents, the design of epitope-based vaccines against infectious diseases, and immunological assays based on peptide antibodies. a large number of methods are available for epitope mapping, but many of them require specialized laboratories and are expensive. in this chapter, we describe a high-throughput approach for epitope mapping of peptide antibodies by use of a library of soluble, overlapping, biotinylate ...201526424277
distribution and transmission of mycobacterium tuberculosis complex lineages among children in peri-urban kampala, uganda.to gain insight into the transmission of tuberculosis (tb) in peri-urban kampala-uganda, we performed a household contact study using children as a surrogate for recent transmission of mycobacterium tuberculosis (mtb). using this approach, we sought to understand m. tuberculosis complex (mtbc) lineage diversity, distribution and how these relate to tb transmission to exposed children.201526424324
revisiting bacterial cyclic nucleotide phosphodiesterases: cyclic amp hydrolysis and beyond.cyclic-3',5'-adenosine monophosphate (camp) is a universal second messenger that regulates vital activities in bacteria and eukaryotes. enzymes that hydrolyze camp, called phosphodiesterases (pdes), negatively regulate the levels of this messenger molecule and are therefore crucial for signal 'termination'. in this minireview, i shall summarize the available literature on bacterial camp-pdes, with particular emphasis on enzymes belonging to the ubiquitously encoded class iii pde family exemplifi ...201526424768
efficacy of adjunctive tofacitinib therapy in mouse models of tuberculosis.the global tuberculosis (tb) epidemic and the spread of multi- and extensively-drug resistant strains of mycobacterium tuberculosis (m.tb) have been fueled by low adherence to following lengthy treatment protocols, and the rapid spread of hiv (human immunodeficiency virus). persistence of the infection in immunocompetent individuals follows from the ability of m.tb to subvert host immune responses in favor of survival within macrophages. alternative host-directed strategies are therefore being c ...201526425693
a mycobacterium tuberculosis dormancy antigen differentiates latently infected bacillus calmette-guérin-vaccinated individuals.ifn-γ release assays (igras) are better indicators of mycobacterium tuberculosis infection than the tuberculin skin test (tst) in bacillus calmette-guérin (bcg)-vaccinated populations. however, igras do not discriminate active and latent infections (ltbi) and no gold standard for ltbi diagnosis is available. thus, since improved tests to diagnose m. tuberculosis infection are required, we assessed the efficacy of several m. tuberculosis latency antigens. bcg-vaccinated healthy donors (hd) and tu ...201526425695
update in mycobacterium tuberculosis lung disease 2014. 201526426784
analysis of the molecular evolution of the mycobacterium tuberculosis drug-resistant gene rpob in asia using a bayesian evolutionary method.tuberculosis (tb) is a serious communicable disease throughout the world. re-emergence of the tb epidemic is aggravated by the circulation of multidrug-resistant mycobacterium tuberculosis strains, and more than half of new cases have occurred in asia. therefore, it is important to understand the gene mutations underlying the development of rifampicin resistance in asia.201526427147
pyrazinamide and pyrazinoic acid derivatives directed to mycobacterial enzymes against tuberculosis.tuberculosis (tb) is an infectious diseases responsible for thousands of deaths worldwide. due to the use of antimycobacterial drugs, tb prevalence seemed to be controlled, but with the appearance of resistant tuberculosis cases, the concern about the disease had become significant again, as well as the need for new alternatives to tb treatment. since pyrazinamide (pza) is part of the firstline agents in tb treatment, several derivatives of this drug were described, besides pyrazinoic acid (poa) ...201626427385
bone marrow aspirate microscopy v. bone marrow trephine biopsy microscopy for detection of mycobacterium tuberculosis infection.tuberculosis (tb) remains a global health problem. according to the 2013 global report on tuberculosis, 8.6 million people developed tb in 2012 and 1.3 million died from the disease. an estimated 13% of people who developed tb in 2012 were hiv-positive, and 75% of these lived in africa. while pulmonary tb is the commonest form of mycobacterium tuberculosis infection, extrapulmonary tb is increasingly being detected in hiv-positive patients. definitive diagnosis of disseminated tb is a challenge ...201526428979
a rare case of concomitant tuberculosis of the nose, paranasal sinuses and larynx: clinical, histological and immunohistochemical aspects. a case report.extrapulmonary tuberculosis is a rare condition determined by mycobacterium tuberculosis. it can affect any organ, and has a higher incidence with the increase of hiv infection, or in countries with high pulmonary tuberculosis. diagnosis is difficult, mostly because of non-specific symptoms and a low rate of presentation for medical consult when symptoms do occur. complete diagnosis is usually set by histological, immunohistochemical examinations, and also with polymerase chain reaction (pcr) in ...201526429181
recognizing drug targets using evolutionary information: implications for repurposing fda-approved drugs against mycobacterium tuberculosis h37rv.drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery. such a cost and time-saving approach gains immense importance for pathogens of special interest, such as mycobacterium tuberculosis h37rv. we report a comprehensive approach to repurpose drugs, based on the exploration of evolutionary relationships inferred from the comparative sequence and structural analyses between targets o ...201526429199
characterization of cd4/cd8+ αβ and vγ2vδ2+ t cells in hiv-negative individuals with different mycobacterium tuberculosis infection statuses.the immune responses of t cell subsets among patients with different mycobacterium tuberculosis (m.tb) infection statuses [i.e., active tuberculosis (atb), latent tuberculosis infection (ltbi) and non-infection (healthy control, hc)] have not been fully elucidated in hiv-negative individuals. specifically, data are limiting in high tuberculosis epidemic regions in china. to investigate the distributions and functions of t cell subsets (i.e., cd3+, cd4+, cd8+ αβ and vγ2vδ2+ t cells) in hiv-negati ...201526429305
genome comparison of an ancestral isolate and a modern isolate of mycobacterium tuberculosis of the beijing lineage from são paulo, brazil.mycobacterium tuberculosis of the bejing subtype (mtbb) is transmitted efficiently in high burden countries for this genotype. a higher virulence was associated with isolates of the "modern" beijing genotype sub-lineages when compared to "ancient" ones. here, we report the full genomes of the strain representing these two genotypes from brazil, a country with a low incidence of mtbb.201526430044
e1 of α-ketoglutarate dehydrogenase defends mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress.enzymes of central carbon metabolism (ccm) in mycobacterium tuberculosis (mtb) make an important contribution to the pathogen's virulence. evidence is emerging that some of these enzymes are not simply playing the metabolic roles for which they are annotated, but can protect the pathogen via additional functions. here, we found that deficiency of 2-hydroxy-3-oxoadipate synthase (hoas), the e1 component of the α-ketoglutarate (α-kg) dehydrogenase complex (kdhc), did not lead to general metabolic ...201526430237
human nocardia infections: a review of pulmonary nocardiosis.human nocardiosis may present as an acute or a chronic infection. although a saprophyte nocardia spp are responsible for superficial skin infections, pulmonary infections, and disseminated nocardiosis usually involving patients who are immunosuppressed and debilitated. infections in immunocompetent individuals are usually chronic and present non-specific symptoms. invasive and disseminated nocardiosis is common among patients with weakened cellular immune systems. clinical diagnosis of pulmonary ...201526430578
performance of four transport and storage systems for molecular detection of multidrug-resistant tuberculosis.detection of drug-resistant tuberculosis is essential for the control of the disease but it is often hampered by the limitation of transport and storage of samples from remote locations to the reference laboratory. we performed a retrospective field study to evaluate the performance of four supports enabling the transport and storage of samples to be used for molecular detection of drug resistance using the genotype mtbdrplus.201526431352
report: clinical characteristics and treatment experience report of severe pulmonary infection after renal transplantation.this study was to discuss the clinical diagnosis and treatment features of severe pulmonary infections after renal transplantation, in order to improve the cure rate. retrospective research was applied to analyze the 52 cases of patients with serve pulmonary infection after renal transplantation in the department of organ transplantation in people's hospital of zhengzhou from july, 2008 to december, 2013. the pathogens which caused the pulmonary infection after renal transplantation were bacteri ...201526431655
identification of bostrycin derivatives as potential inhibitors of mycobacterium tuberculosis protein tyrosine phosphatase (mptpb).as a virulence factor secreted into host cells, the mycobacterium tuberculosis protein tyrosine phosphatase (mptpb) mediates the intracellular survival of m. tuberculosis. mptpb has become an attractive target for the development of new anti-tuberculosis drugs.201626434800
tubercular nodular episcleritis: a case report.tuberculosis (tb) is an infectious disease caused by the acid-fast bacillus mycobacterium tuberculosis and is an important cause of death worldwide. tuberculosis most commonly affects the lungs, but has many extrapulmonary manifestations as well, including intraocular involvement. tubercular nodular episcleritis is a very rare presentation and no such case in an adult male has been reported in the literature. herein, we present the very first case of tubercular nodular episcleritis in a 30-year- ...201526435978
lower respiratory tract infections among hiv positive and control group in nepal.lower respiratory tract infections (lrtis) are the most frequent respiratory diseases among hiv infected patients and are frequently the first clinical manifestations of the hiv infections. lrtis are common not only among the hiv seropositive cases but also the commonest domiciliary and nosocomial infections among the general population. the present study was carried out to determine the comparative prevalence of common bacterial and fungal organism among the hiv positive and control population. ...201526436125
partial saturation of menaquinone in mycobacterium tuberculosis: function and essentiality of a novel reductase, menj.menaquinone (mk) with partially saturated isoprenyl moieties is found in a wide range of eubacteria and archaea. in many gram-positive organisms, including mycobacteria, it is the double bond found in the β-isoprene unit that is reduced. mass spectral characterization of menaquinone from mycobacterial knockout strains and heterologous expression hosts demonstrates that rv0561c (designated menj) encodes an enzyme which reduces the β-isoprene unit of menaquinone in mycobacterium tuberculosis, form ...201526436137
comparative proteomic analysis of aminoglycosides resistant and susceptible mycobacterium tuberculosis clinical isolates for exploring potential drug targets.aminoglycosides, amikacin (ak) and kanamycin (km) are second line anti-tuberculosis drugs used to treat tuberculosis (tb) and resistance to them affects the treatment. membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. in this study we compared membrane and membrane associated proteins of ak and km resistant and susceptible mycobacterium tuberculosis iso ...201526436944
identification and validation of aspartic acid semialdehyde dehydrogenase as a new anti-mycobacterium tuberculosis target.aspartic acid semialdehyde dehydrogenase (asadh) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. mutations in the asadh gene encoding asadh produce an inactive enzyme, which is lethal. therefore, in this study, we investigated the hypothesis that asadh represents a new anti-mycobacterium tuberculosis (mtb) target. an asadh promoter-replacement mutant mtb, designated mtb::asadh, in which asadh gene ...201526437401
mycobacterium tuberculosis nucleic acid amplification tests reduce nosocomial tuberculosis exposure in intensive care units: a nationwide cohort study.this retrospective national surveillance study investigated the burden of and risk factors for nosocomial exposure of pulmonary tuberculosis (tb) in intensive care units.201526437626
profiling serum antibodies to mycobacterium tuberculosis proteins in rhesus monkeys with nontuberculous mycobacteria.recent evidence indicates that the prevalence of diseases caused by nontuberculous mycobacteria (ntm) has been increasing in both human and animals. in this study, antibody profiles of ntm in rhesus monkeys (macaca mulatta) were determined and compared with those of monkeys infected with mycobacterium tuberculosis complex (mtbc). antibodies against 10 m. tuberculosis proteins, purified protein derivative (ppd), and mammalian old tuberculin (mot) were detected in 14 monkeys naturally infected wit ...201626437786
a color-reaction-based biochip detection assay for rif and inh resistance of clinical mycobacterial specimens.the widespread occurrence of drug-resistant mycobacterium tuberculosis places importance on the detection of tb (tuberculosis) drug susceptibility. conventional drug susceptibility testing (dst) is a lengthy process. we developed a rapid enzymatic color-reaction-based biochip assay. the process included asymmetric multiplex pcr/templex pcr, biochip hybridization, and an enzymatic color reaction, with specific software for data operating. templex pcr (tem- pcr) was applied to avoid interference b ...201626437946
pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis.heightened morbidity and mortality in pulmonary tuberculosis (tb) are consequences of complex disease processes triggered by the causative agent, mycobacterium tuberculosis (mtb). mtb modulates inflammation at distinct stages of its intracellular life. recognition and phagocytosis, replication in phagosomes and cytosol escape induce tightly regulated release of cytokines [including interleukin (il)-1, tumor necrosis factor (tnf), il-10], chemokines, lipid mediators, and type i interferons (ifn-i ...201626438324
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