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spoligotyping of mycobacterium tuberculosis isolates at a tertiary care hospital in india.spoligotyping is a valuable genotyping tool to study the genetic diversity and molecular epidemiology of mycobacterium tuberculosis (m. tb). the aim of this study was to analyse different spoligotype patterns of m. tb strains isolated from tuberculosis patients from different parts of india.201728374900
association of esat-6/cfp-10-induced ifn-γ, tnf-α and il-10 with clinical tuberculosis: evidence from cohorts of pulmonary tuberculosis patients, household contacts, and community controls in an endemic setting.mycobacterium tuberculosis (mtb) early secreted protein antigen 6 (esat-6) and culture filtrate protein 10 (cfp-10) are among candidate vaccines against tuberculosis (tb). results of experimental animal models show that these antigens are associated with induction of strong t cell immunity (ifn-γ production), while others report that these proteins as virulent factors involved in pathogenicity of mtb infection. however, the role of esat-6/cfp-10 during natural mtb infections in humans has not be ...201728374535
mycobacterium tuberculosis cell wall fragments released upon bacterial contact with the human lung mucosa alter the neutrophil response to infection.in 2016, the world health organization reported that one person dies of tuberculosis (tb) every 21 s. a host environment that mycobacterium tuberculosis (m.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. we published that human lung mucosa, or alveolar lining fluid (alf), contains an array of hydrolytic enzymes that can significantly alter the m.tb surface during infection by cleaving off parts of its cell wall. t ...201728373877
biosafety level 3 setup for multiphoton microscopy in vivo.multiphoton microscopy has revealed important insights into cellular behavior in vivo. however, its application in infectious settings often encounters technical, safety and regulatory limitations that prevent its wider use with highly virulent human pathogens. herein, we present a method that renders multiphoton microscopy in vivo compatible with biosafety level 3 regulations and present an example of its application and potential to visualize a mycobacterium tuberculosis infection of the mouse ...201728373723
titration of trace amounts of immunoglobulins in a microarray-based assay with magnetic labels.the existing immunoassay format that combines the electrophoretic collection of charged analytes on an antibody microarray with the detection of the bound analytes by magnetic beads coated with secondary antibodies displays extreme sensitivity and speed, but suffers from low precision because of high signal scatter and low signal-to-concentration ratio. here we report three innovations that substantially improve the precision of this method and enable quantitative measurements of analyte concent ...201728372726
chemistry and redox biology of mycothiol.mycothiol (msh, accys-glcn-ins) is the main low molecular weight thiol of most actinomycetes, including the human pathogen mycobacterium tuberculosis that affects millions of people worldwide. strains with decreased msh content show increased susceptibilities to hydroperoxides and electrophilic compounds. in m. tuberculosis, msh modulates the response to several anti-tuberculosis drugs. enzymatic routes involving msh could provide clues for specific drug design. recent advances. physico-chemical ...201728372502
the influence of hiv on the evolution of mycobacterium tuberculosis.hiv significantly affects the immunological environment during tuberculosis co-infection, and therefore may influence the selective landscape upon which m. tuberculosis evolves. to test this hypothesis whole genome sequences were determined for 169 south african m. tuberculosis strains from hiv-1 co-infected and uninfected individuals and analysed using two bayesian codon-model based selection analysis approaches: fubar which was used to detect persistent positive and negative selection (selecti ...201728369607
antimicrobial resistance in mycobacterium tuberculosis: mechanistic and evolutionary perspectives.antibiotic-resistant mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. mycobacterium tuberculosis is intrinsically resistant to many antibiotics, limiting the number of compounds available for treatment. this intrinsic resistance is due to a number of mechanisms including a thick, waxy, hydrophobic cell envelope and the presence of drug degrading and modifying enzymes. resistance to the drugs which are active against m. tuberculosis is, i ...201728369307
galectins and trims directly interact and orchestrate autophagic response to endomembrane damage.macroautophagy/autophagy is a homeostatic process delivering cytoplasmic targets, including damaged organelles, to lysosomes for degradation; however, it is not completely understood how compromised endomembranes are recognized by the autophagic apparatus. we have previously described that the trim family of proteins act as receptors for selective autophagy. in this study we uncovered the property of trims to directly interact with members of the family of cytosolic lectins termed galectins. gal ...201728368693
role of multiplex polymerase chain reaction in diagnosing tubercular meningitis.tuberculous meningitis (tbm) is one of the most serious manifestations of extrapulmonary tuberculosis. timely and accurate diagnosis provides a favorable prognosis in patients with tbm. the study evaluated the use of multiplex polymerase chain reaction (pcr) in the diagnosis of tbm. a study was conducted on 74 patients clinically suspected with tbm. the cerebrospinal fluid (csf) specimens were processed for smear microscopy, middle brook 7h9 culture, and multiplex pcr using primers directed agai ...201728367034
immune-related gene polymorphisms in pulmonary diseases.between the dna sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. during the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (snps), the most common dna variations, and susceptibility to various diseases. because the immune system's primary function is to defend against myriad infec ...201728366820
a high content microscopy assay to determine drug activity against intracellular mycobacterium tuberculosis.tuberculosis is one of the infectious diseases with the greatest global burden, affecting millions of people. the rise of multi- and extensively- drug resistant forms of mycobacterium tuberculosis over the last few decades has highlighted the urgent need for development of new drugs to treat the disease. many drug development pipelines are based on in vitro assays examining a compound's effect on m. tuberculosis alone. these do not account for the effect of a compound on mammalian cells nor the ...201728366666
integrating lung physiology, immunology, and tuberculosis.lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. they are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. as a prototypic host-adapted airborne pathogen, mycobacterium tuberculosis traverses the lung and has several 'interaction points' (ips) whi ...201728366292
evaluation of the antimicrobial activity of cationic polymers against mycobacteria: toward antitubercular macromolecules.antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. tuberculosis, caused by mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. this study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid-arabinogalactan-peptidoglycan comp ...201728365981
diagnostic performance of tuberculosis-specific igg antibody profiles in patients with presumptive tuberculosis from two continents.development of rapid diagnostic tests for tuberculosis is a global priority. a whole proteome screen identified mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. we used world health organization (who) target product profile (tpp) criteria for a detection test and triage test to evaluate these antigens.201728362937
a high-throughput compatible assay to evaluate drug efficacy against macrophage passaged mycobacterium tuberculosis.the early drug development process for anti-tuberculosis drugs is hindered by the inefficient translation of compounds with in vitro activity to effectiveness in the clinical setting. this is likely due to a lack of consideration for the physiologically relevant cellular penetration barriers that exist in the infected host. we recently established an alternative infection model that generates large macrophage aggregate structures containing densely packed m. tuberculosis (mtb) at its core, which ...201728362407
therapy of multidrug-resistant and extensively drug-resistant tuberculosis.the global epidemic of multidrug-resistant tuberculosis (mdr-tb) caused by mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. extensively drug-resistant tuberculosis (xdr-tb), mdr-tb with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of mdr cases globally. cases in india, china, and the russian feder ...201728361737
dna replication in mycobacterium tuberculosis.faithful replication and maintenance of the genome are essential to the ability of any organism to survive and propagate. for an obligate pathogen such as mycobacterium tuberculosis that has to complete successive cycles of transmission, infection, and disease in order to retain a foothold in the human population, this requires that genome replication and maintenance must be accomplished under the metabolic, immune, and antibiotic stresses encountered during passage through variable host environ ...201728361736
assess drug resistance pattern and genetic profile of mycobacterium tuberculosis clinical isolates by molecular typing methods using direct repeats and is6110 in pulmonary tuberculosis cases.tuberculosis (tb), a highly contagious disease that sees no gender, age, or race is mainly a disease of lungs. according to world health organization, a tb patient can be completely cured with 6-9 months of anti-tb treatment under directly observed treatment short course.201728360464
discovery of a new mycobacterium tuberculosis thymidylate synthase x inhibitor with a unique inhibition profile.tuberculosis (tb), mainly caused by mycobacterium tuberculosis (mtb), is an infection that is responsible for roughly 1.5 million deaths per year. the situation is further complicated by the wide-spread resistance to the existing first- and second-line drugs. as a result of this, it is urgent to develop new drugs to combat the resistant bacteria as well as have lower side effects, which can promote adherence to the treatment regimens. targeting the de novo synthesis of thymidylate (dtmp) is an i ...201728359706
diagnosis and treatment of drug-resistant tuberculosis.in the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. the diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. these guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, fr ...201728359606
gold - old drug with new potentials.research into gold-based drugs for a range of human diseases has seen a revival in recent years. this article reviews the most important applications of gold products in the different fields of human pathology. au(i) and au(iii) compounds have been re-introduced in clinical practice for targeting the cellular components involved in the onset and progression of viral and parasitic diseases, rheumatoid arthritis and cancer. this review, after some brief historical notes, takes into account the app ...201728359231
migration of small ligands in globins: xe diffusion in truncated hemoglobin n.in heme proteins, the efficient transport of ligands such as no or o2 to the binding site is achieved via ligand migration networks. a quantitative assessment of ligand diffusion in these networks is thus essential for a better understanding of the function of these proteins. for this, xe migration in truncated hemoglobin n (trhbn) of mycobacterium tuberculosis was studied using molecular dynamics simulations. transitions between pockets of the migration network and intra-pocket relaxation occur ...201728358830
advancing host-directed therapy for tuberculosis.tuberculosis (tb) drug-development strategies, a wide range of candidate host-directed therapies (hdt)s-including new and repurposed drugs, biologics, and cellular therapies-have been proposed to accelerate eradication of infection and overcome the problems associated with current treatment regimens. by investigating the interaction between macrophages and the intracellular parasite toxoplasma gondii (t. gondii), we uncovered that infection-induced signaling pathways suggest possibilities for th ...201728357397
depleting mycobacterium tuberculosis of the transcription termination factor rho causes pervasive transcription and rapid death.rifampicin, which inhibits bacterial rna polymerase, provides one of the most effective treatments for tuberculosis. inhibition of the transcription termination factor rho is used to treat some bacterial infections, but its importance varies across bacteria. here we show that rho of mycobacterium tuberculosis functions to both define the 3' ends of mrnas and silence substantial fragments of the genome. brief inactivation of rho affects over 500 transcripts enriched for genes of foreign dna eleme ...201728348398
quantification of circulating mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring.tuberculosis (tb) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active mycobacterium tuberculosis (mtb) infections in clinically diverse populations and quickly assess mtb treatment responses for emerging drug-resistant strains. we have identified mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nan ...201728348223
unphosphorylated stat1 represses apoptosis in macrophages during mycobacterium tuberculosis infection.in murine macrophages infected with mycobacterium tuberculosis (mtb), the level of phosphorylated stat1 (pstat1) driving the expression of many pro-apoptosis genes, increases quickly but then declines over a period of hours. on the contrary, there is a continued increase of unphosphorylated stat1 (ustat1) that persists for several days. similar trend is discovered between ustat1 level and the intracellular bacterial burden during late infection. to investigate the significance of high level of u ...201728348106
the enigmatic pe/ppe multi-gene family of mycobacteria and tb vaccination.the genome of mycobacterium tuberculosis (mtb), the bacteria responsible for the disease tuberculosis, contains an unusual family of abundant antigens (pe/ppes) . to date certain members of this multigene family occur only in mycobacteria that cause disease. it is possible that the numerous proteins encoded by these mycobacterial genes dictate the immune-pathogenesis of this bacterial pathogen. there is also evidence that some of these antigens are present at the cell surface and that they affec ...201728348055
structure determination of mycobacterium tuberculosis serine protease hip1 (rv2224c).the mycobacterium tuberculosis (mtb) serine protease hip1 (hydrolase important for pathogenesis; rv2224c) promotes tuberculosis (tb) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, mtb groel2. the cell surface localization of hip1 and its immunomodulatory functions make hip1 a good drug target for new adjunctive immune therapies for tb. here, we report the crystal structure of hip1 to a resolution of 2.6 å and the kinetic studies of the enzyme against ...201728346784
comparison of chest ct findings in nontuberculous mycobacterial diseases vs. mycobacterium tuberculosis lung disease in hiv-negative patients with cavities.this article focuses on the differences between ct findings of hiv-negative patients who have cavities with nontuberculous mycobacteria (ntm) disease and those with mycobacterium tuberculosis infections (tb).201728346488
retina and the tubercle bacillus: four decades of our journey and current understanding.tuberculosis continues to be a major pandemic with enormous public health implication. involvement of ocular tissues in the form of tubercles, tuberculomas, panophthalmitis, and iris granulomas are well recognized as definitive manifestations of tuberculosis. for these lesions, confirmatory evidence is available in the form of demonstration of acid-fast bacillus on ziehl-neelsen staining. for other retinochoroidal disorders such as central serous chorioretinopathy, retinal vasculitis, and presum ...201728345567
diagnostic significance of mycobacterium tuberculosis t-cell assays for active tuberculosis.active tuberculosis (tb) with negative results of sputum smear is difficult to be identified. till now, there is no effective and noninvasive diagnostic method. this study evaluated the diagnostic power of mycobacterium tuberculosis t-cell (t.spot®.tb) assays for active tb.201728345545
prevalence and risk factors of multi-drug resistant tuberculosis in dalian, china.objectives to investigate the prevalence and risk factors associated with multi-drug resistant tuberculosis (mdr-tb) in dalian, china. methods this was a retrospective review of data from patients attending a tb clinic in dalian, china between 2012 and 2015. demographic and drug susceptibility data were retrieved from tb treatment cards. univariate logistic analysis was used to assess the association between risk factors and mdr-tb. results among the 3552 patients who were smear positive for myc ...201728345426
splenic vein thrombosis as a rare complication of disseminated tuberculosis - imaging diagnosis and case report.venous thromboembolism is a known but rare complication associated with mycobacterium tuberculosis infection. the reported incidence of venous thromboembolism is 1.5-3.4% of infected patients, and it occurs due to a hypercoagulable state induced by the associated inflammation.201728344684
in vitro and in vivo fitness costs associated with mycobacterium tuberculosis rpob mutation h526d.there is controversy regarding the potential fitness costs of rifampicin (rif) resistance-conferring mutations in the mycobacterium tuberculosis (mtb) rpob gene. we characterized the pathogenicity of an mtb rpob h526d mutant.201728343421
association between parasitic infections and tuberculin skin test results in refugees.parasitic infections are known to modulate the immune response necessary for controlling mycobacterium tuberculosis infection. we sought to investigate species-specific effects of parasite infection on m. tuberculosis infection.201728342825
mutation analysis of the interactions between mycobacterium tuberculosis caseinolytic protease c1 (clpc1) and ecumicin.ecumicin is a well-known and potent inhibitor of mycobacterium tuberculosis. although the target of ecumicin is caseinolytic protease c1 (clpc1), the exact mechanism by which ecumicin inhibits clpc1 has not been identified. to analyze ecumicin's action on clpc1, site-directed mutagenesis was performed on its binding site. the estimated binding residues within clpc1 to ecumicin were selected via in silico analysis using molecular docking. the selected residues were mutated by site-directed mutage ...201728342755
sendai virus mucosal vaccination establishes lung-resident memory cd8 t cell immunity and boosts bcg-primed protection against tb in mice.accumulating evidence has shown the protective role of cd8(+) t cells in vaccine-induced immunity against mycobacterium tuberculosis (mtb) despite controversy over their role in natural immunity. however, the current vaccine bcg is unable to induce sufficient cd8(+) t cell responses, especially in the lung. sendai virus, a respiratory rna virus, is here engineered firstly as a novel recombinant anti-tb vaccine (sev85ab) that encodes mtb immuno-dominant antigens, ag85a and ag85b. a single mucosal ...201728342639
anti-tubercular drug discovery: in silico implications and challenges.tuberculosis (tb) has been reported as a major public health concern, especially in the developing countries. who report on tuberculosis 2016 shows a high mortality rate caused by tb leading to 1.8 million deaths worldwide (including deaths due to tb in hiv positive individuals), which is one of the top 10 causes of mortality in 2015. however, the main therapy used for the treatment of tb is still the direct observed therapy short-course (dots) that consists of four main first-line drugs. due to ...201728341614
the diverse family of mmpl transporters in mycobacteria: from regulation to antimicrobial developments.mycobacterial genomes contain large sets of loci encoding membrane proteins that belong to a family of multidrug resistance pumps designated resistance-nodulation-cell division (rnd) permeases. mycobacterial membrane protein large (mmpl) transporters represent a subclass of rnd transporters known to participate in the export of lipid components across the cell envelope. these surface-exposed lipids with unusual structures play key roles in the physiology of mycobacteria and/or can act as virulen ...201728340510
synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine mannich bases.in this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine mannich bases (7a-v). the mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in acoh. the chemical structures of the compounds were characterized by (1)h nmr, (13)c nmr, lc/ms and elemental analysis. single crystal x-ray diffraction has been recorded for com ...201728340368
a nonsynonymous snp catalog of mycobacterium tuberculosis virulence genes and its use for detecting new potentially virulent sublineages.mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as is-elements, vntr, and snps are used for lineage identification. we propose an m. tuberculosis classification approach based on functional polymorphisms in virulence genes. an m. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antit ...201728338924
clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic-resistant mycobacterium tuberculosis infections.first extensive reformulation of clofazimine (clz) in nanoporous silica particles (nsps) for tackling antibiotic-resistant tuberculosis (tb) infections.201728338408
resuscitation-promoting factors are important determinants of the pathophysiology in mycobacterium tuberculosis infection.resuscitation promoting factors (rpf) are peptidoglycan-hydrolyzing enzymes that are pivotal in the resuscitation of quiescent actinobacteria including mycobacterium tuberculosis. from the published data, it is clear that rpf are required for the resuscitation of non-replicating bacilli and pathogenesis in murine infection model of tuberculosis, although their direct influence on human mycobacterium tuberculosis infection is ill-defined. in this review, we describe the progress in the understand ...201728338360
acid-fast positive and acid-fast negative mycobacterium tuberculosis: the koch paradox.acid-fast (af) staining, also known as ziehl-neelsen stain microscopic detection, developed over a century ago, is even today the most widely used diagnostic method for tuberculosis. herein we present a short historical review of the evolution of af staining methods and discuss koch's paradox, in which non-af tubercle bacilli can be detected in tuberculosis patients or in experimentally infected animals. the conversion of mycobacterium tuberculosis from an actively growing, af-positive form to a ...201728337966
genotypic diversity of mycobacterium tuberculosis clinical isolates in the multiethnic area of the xinjiang uygur autonomous region in china.objectives. we studied the genetic diversity of clinical isolates from patients with tuberculosis in the multiethnic area of xinjiang autonomous region in china. a total of 311 clinical m. tuberculosis isolates were collected in 2006 and 2011 and genotyped by two genotyping methods. all isolates were grouped into 68 distinct spoligotypes using the spoligotyping method. the beijing family was dominant, followed by t1 and cas. miru-vntr results showed that a total of 195 different vntr types were ...201728337447
3-substituted n-benzylpyrazine-2-carboxamide derivatives: synthesis, antimycobacterial and antibacterial evaluation.a series of substituted n-benzyl-3-chloropyrazine-2-carboxamides were prepared as positional isomers of 5-chloro and 6-chloro derivatives, prepared previously. during the aminolysis of the acyl chloride, the simultaneous substitution of chlorine with benzylamino moiety gave rise to n-benzyl-3-(benzylamino)pyrazine-2-carboxamides as side products, in some cases. although not initially planned, the reaction conditions were modified to populate this double substituted series. the final compounds we ...201728335571
combination effect of antituberculosis drugs and ethanolic extract of selected medicinal plants against multi-drug resistant mycobacterium tuberculosis isolates.adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. this research aimed to find the combination effect of standard antituberculosis drugs with hibiscus sabdariffa l., kaempferia galanga l., and piper crocatum n.e. br against multi-drug resistant (mdr) mycobacterium tuberculosis isolates. two mdr strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of m. tuberculosis were inoculated in löwenstein-jen ...201728335544
statistical analysis of genetic interactions in tn-seq data.tn-seq is an experimental method for probing the functions of genes through construction of complex random transposon insertion libraries and quantification of each mutant's abundance using next-generation sequencing. an important emerging application of tn-seq is for identifying genetic interactions, which involves comparing tn mutant libraries generated in different genetic backgrounds (e.g. wild-type strain versus knockout strain). several analytical methods have been proposed for analyzing t ...201728334803
swga: a primer design toolkit for selective whole genome amplification.population genomic analyses are often hindered by difficulties in obtaining sufficient numbers of genomes for analysis by dna sequencing. selective whole-genome amplification (swga) provides an efficient approach to amplify microbial genomes from complex backgrounds for sequence acquisition. however, the process of designing sets of primers for this method has many degrees of freedom and would benefit from an automated process to evaluate the vast number of potential primer sets.201728334194
relapse, re-infection and mixed infections in tuberculosis disease.tuberculosis (tb) disease can be characterized by genotypic and phenotypic complexity in mycobacterium tuberculosis bacilli within a single patient. this microbiological heterogeneity has become an area of intense study due its perceived importance in drug tolerance, drug resistance and as a surrogate measure of transmission rates. this review presents a descriptive analysis of research describing the prevalence of mixed strain tb infections in geographically distinct locations. despite signific ...201728334088
association between genotype and drug resistance profiles of mycobacterium tuberculosis strains circulating in china in a national drug resistance survey.we describe the population structure of a representative collection of 3,133 mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in china. genotyping data indicate that the epidemic strains in china can be divided into seven major complexes, of which 92% belonged to the east asian (mainly beijing strains) or the euro-american lineage. the epidemic beijing strains in china are closely related to the beijing b0/w148 strain earlier described ...201728333978
activity of faropenem with and without rifampicin against mycobacterium tuberculosis: evaluation in a whole-blood bactericidal activity trial.faropenem has in vitro activity against mycobacterium tuberculosis (mtb) and shows synergy with rifampicin. we tested this in a whole-blood bactericidal activity (wba) trial.201728333342
susceptibilities of mdr mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters.the second-line drugs recommended to treat drug-resistant tb are toxic, expensive and difficult to procure. given increasing resistance, the need for additional anti-tb drugs has become more urgent. but new drugs take time to develop and are expensive. some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse.201728333192
toll-like receptor-2 arg753gln and arg677trp polymorphisms and susceptibility to pulmonary and peritoneal tuberculosis.recent evidence suggests that toll-like receptor-2 (tlr2) is important for host defense against mycobacterium tuberculosis (mtb). tlr2 polymorphisms have shown significant impact on susceptibility or resistance to tuberculosis (tb). this case-control study aims to determine the influence of tlr2 (arg753gln and arg677trp) polymorphisms on the susceptibility to develop pulmonary or peritoneal tb. genotyping of tlr2 (arg753gln and arg677trp) polymorphisms was carried out on 52 patients with pulmona ...201728332241
public health relevance of non-tuberculous mycobacteria among afb positive sputa.sputum smear microscopy for acid fast bacilli (afb) is used by most public health programmes to detect tuberculosis. while most afb in countries endemic for tuberculosis are mycobacterium tuberculosis (mtb), some may also be non-tuberculous mycobacteria (ntm). the inability to differentiate ntm from mtb by sputum smear microscopy may lead to erroneous diagnoses of tuberculosis, leading in turn to inappropriate therapy.201728331837
molecular detection of multidrug-resistant tuberculosis among smear-positive pulmonary tuberculosis patients in jigjiga town, ethiopia.molecular methods that target drug resistance mutations are suitable approaches for rapid drug susceptibility testing to detect multidrug-resistant tuberculosis (mdr-tb). the aim of the study was to determine mdr-tb cases and to analyze the frequency of gene mutations associated with rifampicin (rif) and/or isoniazid (inh) resistance of mycobacterium tuberculosis among smear-positive pulmonary tuberculosis patients.201728331348
direct detection of rifampicin and isoniazid resistance in sputum samples from tuberculosis patients by high resolution melt curve analysis.drug-resistant tuberculosis (tb) is a major threat for tb control worldwide. globally, only 40% of the 340,000 notified tb patients estimated to have multidrug resistant-tb (mdr-tb) were detected in 2015. this study was carried out to evaluate the utility of high resolution melt curve analysis (hrm) for the rapid and direct detection of mdr-tb in mycobacterium tuberculosis (m. tb) in sputum samples. a reference plasmid library was first generated of the most frequently observed mutations in the ...201728330890
revaccination of guinea pigs with the live attenuated mycobacterium tuberculosis vaccine mtbvac improves bcg's protection against tuberculosis.the need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. novel live attenuated vaccines are being developed that promise greater safety and efficacy than bcg against tuberculosis. we combined bcg with the vaccine mtbvac to evaluate whether the efficacy of either vaccine would be affected upon revaccination.201728329234
bacterial immunostat: mycobacterium tuberculosis lipids and their role in the host immune response.the lipid-rich cell wall of mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. it is therefore postulated to contribute to the long-term bacterial survival in an infected human host. accumulating evidence suggests that m. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. some of these lipid species (treh ...201728327797
risk factors for latent tuberculosis infection (ltbi) in health profession's students of the university of parma.nowadays tuberculosis (tb) is one of the major public health problems for several professional categories. according to italian law, university students are compared to workers: the main risk for them is represented by biological risk, in particular by blood-transmitted or by air-transmitted agents. as for tb, many scientific studies demonstrated that prevalence of latent tuberculosis infection (ltbi) in medicine and surgery students was lower than those in health workers and in general populati ...201728327495
mir-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through tlr2/myd88/nf-κb pathway by targeting tlr2.autophagy plays a pivotal role in activating the antimicrobial host defense against mycobacterium tuberculosis (m.tb.). the emerging roles of micrornas (mirnas) in regulating immune responses have attracted increasing attention in recent years. appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of mir-23a-5p on the activation of macrophage autophagy during m.tb. infection in bone marrow-derived macrophag ...201728327409
preliminary evaluation of anti-tuberculosis potential of siderophores against drug-resistant mycobacterium tuberculosis by mycobacteria growth indicator tube-drug sensitivity test.alternative treatment strategies have become essential in overcoming the problem of drug-resistant mycobacterium tuberculosis (mtb). in this preliminary in vitro study, the anti-tuberculosis (anti-tb) activity of exogenous iron chelators (xenosiderophores) such as exochelin-ms (exo-ms) and deferoxamine-b (dfo-b) was evaluated against ten multi-drug-resistant (mdr) and seven pyrazinamide-resistant (pza (r) ) mtb isolates.201728327117
chitosan gold nanoparticles for detection of amplified nucleic acids isolated from sputum.a platform for nucleic acid detection employing chitosan and chitosan coated gold nanoparticles (aunps) was developed. mycobacterium tuberculosis (mtb) was used as a model target. mtb dna was extracted from sputum using simple total nucleic acid extraction. following amplification of mtb dna, chitosan and aunps were added to samples. free chitosan conjugated non-target dna in negative samples, avoiding aunp-dna interaction and hence negative samples remained red. in positive samples, amplified d ...201728325344
letter to the editor concerning: garg p. comparison of histopathology and real-time polymerase chain reaction (rt-pcr) for detection of mycobacterium tuberculosis in fistula-in-ano (int j colorectal dis. 2017 feb 16. doi: 10.1007/s00384-017-2783-y. [epub ahead of print]). 201728324137
expression, maturation and turnover of drrs, an unusually stable, dosr regulated small rna in mycobacterium tuberculosis.mycobacterium tuberculosis depends on the ability to adjust to stresses encountered in a range of host environments, adjustments that require significant changes in gene expression. small rnas (srnas) play an important role as post-transcriptional regulators of prokaryotic gene expression, where they are associated with stress responses and, in the case of pathogens, adaptation to the host environment. in spite of this, the understanding of m. tuberculosis rna biology remains limited. here we ha ...201728323872
systematic expression profiling analysis mines dys-regulated modules in active tuberculosis based on re-weighted protein-protein interaction network and attract algorithm.about 90% of tuberculosis (tb) patients latently infected with mycobacterium tuberculosis (mtb) show no symptoms, yet have a 10% chance in lifetime to progress active tb. nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. the objective of this work was to detect potential signatures for active tb to further improve the understanding of the biological roles of functional modules involved in this disease. first, targeted networks of active tb and control gro ...201728323150
modulation of central carbon metabolism by acetylation of isocitrate lyase in mycobacterium tuberculosis.several enzymes involved in central carbon metabolism such as isocitrate lyase and phosphoenolpyruvate carboxykinase are key determinants of pathogenesis of mycobacterium tuberculosis (m. tb). in this study, we found that lysine acetylation plays an important role in the modulation of central carbon metabolism in m. tb. mutant of m. tb defective in sirtuin deacetylase exhibited improved growth in fatty acid-containing media. global analysis of lysine acetylome of m. tb identified three acetylate ...201728322251
primary clofazimine and bedaquiline resistance among isolates from patients with multidrug-resistant tuberculosis.clofazimine has been repurposed for the treatment of tuberculosis especially for mdr-tb. to test the susceptibility to clofazimine for mycobacterium tuberculosis clinical isolates, mics of clofazimine were determined using the microplate alamar blue assay (maba) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. five clofazimine-resistant strains isolated from previously treated pre-xdr and xdr-tb patients without prior exposure to clofazimine or bedaquiline h ...201728320727
prevalence of tuberculous lesion in cattle slaughtered in mubende district, uganda.the aim of this study was to estimate the prevalence of gross pathology suggestive of bovine tuberculosis (tb-like lesions) and evaluate animal's characteristics associated with the risk of having bovine tb-like lesions among cattle slaughtered in mubende district in the uganda cattle corridor.201728320401
diagnostic accuracy, incremental yield and prognostic value of determine tb-lam for routine diagnostic testing for tuberculosis in hiv-infected patients requiring acute hospital admission in south africa: a prospective cohort.we previously reported that one-third of hiv-positive adults requiring medical admission to a south african district hospital had laboratory-confirmed tuberculosis (tb) and that almost two-thirds of cases could be rapidly diagnosed using xpert mtb/rif-testing of concentrated urine samples obtained on the first day of admission. implementation of urine-based, routine, point-of-care tb screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, s ...201728320384
multidrug resistant tuberculosis in ethiopian settings and its association with previous history of anti-tuberculosis treatment: a systematic review and meta-analysis.efforts to control the global burden of tuberculosis (tb) have been jeopardized by the rapid evolution of multi-drug resistant mycobacterium tuberculosis (mtb), which is resistant to at least isoniazid and rifampicin. previous studies have documented variable prevalences of multidrug-resistant tuberculosis (mdr-tb) and its risk factors in ethiopia. therefore, this meta-analysis is aimed, firstly, to determine the pooled prevalence of mdr-tb among newly diagnosed and previously treated tb cases, ...201728320336
vision loss in tuberculous meningitis.vision loss is a disabling complication of tuberculous meningitis. approximately, 15% of survivors are either completely or partially blind. all structures of the visual pathway may be affected in tuberculous meningitis. optic nerve and optic chiasma are most frequently and dominantly affected. thick-gelatinous exudates lying over the base of brain, are the pathological hallmark of tuberculous meningitis and are responsible for almost all of its major complications, including vision loss. strang ...201728320145
ventriculo-peritoneal shunt surgery for tuberculous meningitis: a systematic review.ventriculo-peritoneal shunt surgery is one of the most commonly performed surgery for the management of tuberculous hydrocephalus. there is decreased clarity on issues regarding the indication as well as timing of cerebrospinal fluid diversion procedures in tuberculous meningitis. we systematically analysed published literature on this subject with an objective to assess the value of cerebrospinal fluid diversion procedures in tuberculous meningitis.201728320142
antibody response against phop efficiently discriminates among healthy individuals, tuberculosis patients and their contacts.tuberculosis continues to be one of the most devastating global health problem. its diagnosis will benefit in timely initiation of the treatment, cure and therefore reduction in the transmission of the disease. tests are available, but none can be comprehensively relied on for its diagnosis; especially in tb-endemic zones. phop is a key player in mycobacterium tuberculosis virulence but nothing has been known about its role in the diagnosis of tb. we monitored the presence of anti-phop antibodie ...201728319170
rapid diagnosis of tuberculosis. detection of drug resistance mechanisms.tuberculosis is still a serious public health problem, with 10.8 million new cases and 1.8 million deaths worldwide in 2015. the diversity among members of the mycobacterium tuberculosis complex, the causal agent of tuberculosis, is conducive to the design of different methods for rapid diagnosis. mutations in the genes involved in resistance mechanisms enable the bacteria to elude the treatment. we have reviewed the methods for the rapid diagnosis of m. tuberculosis complex and the detection of ...201728318570
hemophagocytic syndrome secondary to tuberculosis at 24-week gestation.hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. a 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°f of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for mycobacterium tuberculosis. ...201728317816
the medicinal plants in the control of tuberculosis: laboratory study on medicinal plants from the northern area of pakistan.tuberculosis (tb) ranks as the second leading cause of deaths due to infectious diseases. although global efforts have been made to control tb, still, this is a serious threat as mycobacterium tuberculosis (mtb) produced resistance against both the first- and second-line drugs. the increasing incidence of multidrug-resistant, extremely drug resistant, and totally drug-resistant tb worldwide requires extra efforts to search for new anti-tb drugs.201728317814
association between pulmonary tuberculosis and type 2 diabetes in sudanese patients.tuberculosis (tb) and diabetes mellitus (dm) are both important health issues, and the association between dm and tb may be the next challenge for global tb control worldwide, type 2 dm (t2dm) responsible for 90% of dm cases. persons with diabetes have a significantly increased risk of active tb, which is two to three times higher than in persons without diabetes. the aim of this study was to determine the association between pulmonary tuberculosis (ptb) and t2dm among sudanese patients and also ...201728317813
performance of the xpert mtb/rif assay in the diagnosis of tuberculosis in formalin-fixed, paraffin-embedded tissues.extrapulmonary tuberculosis (eptb), which accounts for 10%-40% of the global burden of tb, with the highest incidence in sub-saharan africa, is strongly associated with human immunodeficiency virus infection. diagnosing eptb is challenging, and recently, there has been a concerted effort to evaluate the latest molecular diagnostics for diagnosing tb in a range of specimen types. the xpert mtb/rif assay (cepheid, sunnyvale, ca, usa) is one such technology, which simultaneously detects mycobacteri ...201728317811
prevalence and genetic determinant of drug-resistant tuberculosis among patients completing intensive phase of treatment in a tertiary referral center in nigeria.drug-resistant tuberculosis (dr-tb) continues to be a challenge in developing countries with poor resources. despite the high prevalence of primary dr-tb, its routine screening prior to the treatment is not performed in public hospitals in nigeria. data regarding drug resistance and its genetic determinant among follow-up patients with tb are lacking in nigeria. hence, the aim of this study was to determine the prevalence and genetic determinant of drug resistance among the follow-up patients wi ...201728317805
a first insight into the genetic diversity of mycobacterium tuberculosis in veracruz, mexico.tuberculosis (tb) remains one of the most important infectious diseases. although mexico is one of the latin american countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of tb. the aim of this study was to use the miru-vntr-24 loci to analyze the genetic diversity of m. tuberculosis circulating in the state of veracruz, mexico.201728317799
nontuberculous mycobacterial species and mycobacterium tuberculosis complex coinfection in patients with pulmonary tuberculosis in dr. soetomo hospital, surabaya, indonesia.the aim of this study was to analyze the detection of nontuberculous mycobacterial (ntm) species derived from sputum specimens of pulmonary tuberculosis (tb) suspects. increasing prevalence and incidence of pulmonary infection by ntm species have widely been reported in several countries with geographical variation.201728317798
molecular characteristics of ofloxacin mono-resistant mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients.ofloxacin (ofx) resistant mycobacterium tuberculosis (mtb) isolates have been increasingly observed and are a major concern in recent years. this study investigated the genetic mutations associated with ofx resistance among clinical ofx mono-resistant mtb isolates from new and previously treated tuberculosis patients.201728317169
sequence-based hla-a, b, c, dp, dq, and dr typing of 100 luo infants from the boro area of nyanza province, kenya.one hundred healthy infants enrolled as controls in a tuberculosis vaccine study in nyanza province, kenya provided anonymized samples for dna sequence-based typing at the hla-a, -b, -c, -dpb1, -dqa1, -dqb1, -drb1, and -drb3/4/5 loci. the purpose of the study was to characterize allele frequencies in the local population, to support studies of t cell immunity against pathogens, including mycobacterium tuberculosis. there are no detectable deviations from hardy weinberg proportions for the hla-b, ...201728315719
comparative analysis of internalisation, haemolytic, cytotoxic and antibacterial effect of membrane-active cationic peptides: aspects of experimental setup.cationic peptides proved fundamental importance as pharmaceutical agents and/or drug carrier moieties functioning in cellular processes. the comparison of the in vitro activity of these peptides is an experimental challenge and a combination of different methods, such as cytotoxicity, internalisation rate, haemolytic and antibacterial effect, is necessary. at the same time, several issues need to be addressed as the assay conditions have a great influence on the measured biological effects and t ...201728314993
secretory proteome analysis of streptomycin-resistant mycobacterium tuberculosis clinical isolates.tuberculosis still remains one of the most fatal infectious diseases. streptomycin (sm) is the drug of choice, especially for patients with multidrug-resistant tuberculosis or category ii patients, because it targets the protein synthesis machinery by interacting with steps of translation. several mechanisms have been proposed to explain the resistance, but our knowledge is inadequate. secretome often plays an important role in pathogenesis and is considered an attractive reservoir for the devel ...201728314116
fragment-sized ethr inhibitors exhibit exceptionally strong ethionamide boosting effect in whole-cell mycobacterium tuberculosis assays.small-molecule inhibitors of the mycobacterial transcriptional repressor ethr have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. fragment-based drug discovery approaches have been used in the past to make highly potent ethr inhibitors with ethionamide boosting activity both in vitro and ex vivo. herein, we report the development of fragment-sized ethr ligands with nanomolar minimum effective concentration values for boosting the ethionamide activi ...201728314097
hypervirulent mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant c57bl/6 mice.tuberculosis (tb) is a chronic infectious disease caused by mycobacterium tuberculosis (mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. the murine model of tb in resistant c57bl/6 mice infected with reference mtb strains is widely used in tb studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. recently, we demonstrated that necrotic lung lesions coul ...201728306733
elevation of fumarate levels compromise redox control and viability in mycobacterium tuberculosis.in this issue of cell chemical biology, ruecker et al. (2017) show that fumarase depletion in mycobacterium tuberculosis leads to fumarate, a tca cycle intermediate, accumulation, causing succination of a range of thiol-containing metabolites and proteins. fumarate is bactericidal to the pathogen, and its accumulation may enhance the bactericidal effector mechanisms of other tca cycle intermediates that accumulate due to activation of infected macrophages.201728306498
rational design, synthesis and biological evaluation of heterocyclic quinolones targeting the respiratory chain of mycobacterium tuberculosis.a high-throughput screen (hts) was undertaken against the respiratory chain dehydrogenase component, nadh:menaquinone oxidoreductase (ndh) of mycobacterium tuberculosis (mtb). 11,000 compounds were selected for the hts based on the known phenothiazine ndh inhibitors, trifluoperazine and thioridazine. combined hts (11,000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified ~100 hits and four distinct chemotypes, the most promising of which contained the q ...201728304162
diagnostic dilemma of granulomatous inflammation in cancer patients.to determine the frequency of granulomatous inflammation on histopathological findings amongst cancer patients and correlating them with tuberculosis.201728303990
trends in spoligotype patterns of mycobacterium tuberculosis strains in central india.this study aims to understand trends in spoligotype patterns of mycobacterium tuberculosis (mtb) in central india. elucidation of these trends may provide baseline information to understand the transmission dynamics of strains of mtb in the region. spoligotyping was carried out on 340 mtb strains isolated from clinical samples received from 2007 to 2011. the prevalence of st26/cas1_del, st11/eai3_ind, st288/cas2, st25/cas1_del and beijing lineages showed waxing and waning trends. st26/cas1_del a ...201728303834
detection of ofloxacin resistance by nitrate reductase assay in mycobacterium tuberculosis isolates from extrapulmonary tuberculosis.increased use of fluoroquinolones to treat community-acquired infections has led to the decreased susceptibility to mycobacterium tuberculosis. there is a paucity of data on ofloxacin (ofx) resistance detection by nitrate reductase assay (nra). hence, the present study was carried out to find the efficacy of nra for detection of ofx resistance in m. tuberculosis isolated from extrapulmonary tuberculosis (eptb) cases.201728303821
spoligotype defined lineages of mycobacterium tuberculosis and drug resistance: merely a casual correlation?drug-resistant tuberculosis (tb) is a major challenge to tb control strategy worldwide. analysis of genetic polymorphism among drug resistant mycobacterium tuberculosis (mtb) strains may help provide some insight into the transmission dynamics of these strains. spoligotyping is a widely used technique to identify genetic polymorphism, based on 43 known spacers interspersed between direct repeat regions. considerable work has been done in various parts of the world using this technique to identif ...201728303814
delays in diagnosis and treatment of pulmonary tuberculosis in afb smear-negative patients with pneumonia.<h2>background:</h2><p>diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (ptb). this study aimed to evaluate tb diagnostic and treatment delays in acid-fast bacilli (afb) smear-negative patients.</p><h2>methods:</h2><p>this was a retrospective observational study. patients with positive afb culture of <i>mycobacterium tuberculosis</i> complex (mtc) were selected from among hospitalised patients with a diagnosis of pneumonia. admission ward, anti-tub ...201728303781
mutations in catalase-peroxidase katg from isoniazid resistant mycobacterium tuberculosis clinical isolates: insights from molecular dynamics simulations.the current multidrug therapy for tuberculosis (tb) is based on the use of isoniazid (inh) in combination with other antibiotics such as rifampin, ethambutol and pyrazinamide. literature reports have shown that mycobacterium tuberculosis, the causative agent of tb, has become resistant to this treatment by means of point mutations in the target enzymes of these drugs, such as catalase-peroxidase (katg). by means of equilibrium molecular dynamics in the presence of the ligand, this work evaluated ...201728303436
reversion of antibiotic resistance in mycobacterium tuberculosis by spiroisoxazoline smart-420.antibiotic resistance is one of the biggest threats to human health globally. alarmingly, multidrug-resistant and extensively drug-resistant mycobacterium tuberculosis have now spread worldwide. some key antituberculosis antibiotics are prodrugs, for which resistance mechanisms are mainly driven by mutations in the bacterial enzymatic pathway required for their bioactivation. we have developed drug-like molecules that activate a cryptic alternative bioactivation pathway of ethionamide in m. tube ...201728302858
alternative quantiferon cytokines for diagnosis of children with active tuberculosis and hiv co-infection in ghana.ifn-γ release assays (igras) often present false-negative or indeterminate results in children with tuberculosis. hiv co-infection may contribute to decreased sensitivity of igras by impairing t-cell ifn-γ expression. measurement of alternative cytokines in quantiferon(®) (qft) supernatants can circumvent the ifn-γ-dependency and may improve qft sensitivity. we aimed to identify additional cytokines from qft supernatants for detection of mycobacterium tuberculosis infection in children with tube ...201728299430
effects of ifn-β1a and ifn-β1b treatment on the expression of cytokines, inducible nos (nos type ii), and myelin proteins in animal model of multiple sclerosis.the aim of this study was to investigate the effects of interferon (ifn)-β1a and ifn-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the lewis rat experimental autoimmune encephalomyelitis (eae), animal model of multiple sclerosis. to induce eae, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an ...201728299403
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