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interplay between mutations and efflux in drug resistant clinical isolates of mycobacterium tuberculosis.numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of mycobacterium tuberculosis is poorly understood and still is ignored by many. here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resis ...201728496433
the uniqueness of subunit α of mycobacterial f-atp synthases: an evolutionary variant for niche adaptation.the f1f0 -atp (f-atp) synthase is essential for growth of mycobacterium tuberculosis, the causative agent of tuberculosis (tb). in addition to their synthase function most f-atp synthases possess an atp-hydrolase activity, which is coupled to proton-pumping activity. however, the mycobacterial enzyme lacks this reverse activity, but the reason for this deficiency is unclear. here, we report that a mycobacterium-specific, 36-amino acid long c-terminal domain in the nucleotide-binding subunit α (m ...201728495884
role of apoptosis and autophagy in tuberculosis.tuberculosis (tb) is one of the oldest known human diseases and is transmitted by the bacteria mycobacterium tuberculosis (mtb). tb has a rich history with evidence of tb infections dating back to 5,800 bc tb is unique in its ability to remain latent in an individual for decades, with the possibility of later reactivation, causing widespread systemic symptoms. currently, it is estimated that more than one-third of the world's population (~2 billion people) are infected with mtb. prolonged period ...201728495854
small molecule efflux pump inhibitors in mycobacterium tuberculosis: a rational drug design perspective.drug resistance in mycobacterium tuberculosis (m. tuberculosis) complicates management of tuberculosis. efflux pumps contribute to low level resistance and acquisition of additional high level resistance mutations through sub-therapeutic concentrations of intracellular antimycobacterials. various efflux pump inhibitors (epis) have been described for m. tuberculosis but little is known regarding the mechanism of efflux inhibition. as knowledge relating to the mechanism of action and drug target i ...201728494730
recent developments of coumarin-containing derivatives and their anti-tubercular activity.tuberculosis (tb) is a lift-threatening chronic deadliest infectious disease caused predominantly by mycobacterium tuberculosis (mtb) which affects primarily the lungs (pulmonary tb) apart from other vital organs. the emergence of drug-resistant tb (dr-tb), multidrug-resistant tb (mdr-tb), extensively drug-resistant tb (xdr-tb) and the recently cases of totally drug resistant (tdr) towards currently accessible standard drugs was increased up to alarming level in the recent decades. in pursuit of ...201728494250
a rab20-dependent membrane trafficking pathway controls m. tuberculosis replication by regulating phagosome spaciousness and integrity.the intracellular pathogen mycobacterium tuberculosis (mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. the host pathways and mechanisms that contribute to maintaining mtb phagosome integrity have not been investigated. here, we examined the spatiotemporal dynamics of mtb-containing phagosomes and identified an interferon-gamma-stimulated and rab20-dependent membrane trafficking pathway in macrophages that maintains mtb in spacious proteolytic phagolysosomes ...201728494243
mest, a unique epoxide hydrolase, is essential for optimal growth of mycobacterium tuberculosis in the presence of styrene oxide.mest of mycobacterium tuberculosis, a hypothetical/putative epoxide hydrolase, is predicted to convert toxic epoxides to the more water-soluble and less toxic diols. detailed characterization of the protein was carried out.201728492351
the path of least antibiotic resistance.antibiotic combination therapy alters mycobacterium tuberculosis population dynamics in the human host.201728490666
evaluation of xpert mtb/rif assay in children with presumed pulmonary tuberculosis in papua new guinea.the gene xpert mtb/ rif assay (xpert) is used for rapid, simultaneous detection of mycobacterium tuberculosis (mtb) and rifampicin resistance. this study examined the accuracy of xpert in children with suspected pulmonary tuberculosis (ptb).201728490246
penetrating gastric ulcer as a manifestation of multisystemic tuberculosis.we present the case of a 30-year old female with a history of abdominal pain, fever, poor oral tolerance and weight loss for 6 months. an abdominal ct scan showed marked gastric dilatation due to extrinsic compression from lymphadenopathies around the second portion of the duodenum. the upper endoscopy revealed the presence of a penetrating gastric ulcer in the greater curvature. biopsies of the lesions showed hystiocytes with granulomatous features and acid fast bacilli (afb) positive, and the ...201728489844
risk factors associated with multidrug-resistant tuberculosis in espírito santo, brazil.to analyze the prevalence and factors associated with multidrug-resistant tuberculosis in espírito santo, brazil.201728489185
v67l mutation fills an internal cavity to stabilize reca mtu intein.inteins mediate protein splicing, which has found extensive applications in protein science and biotechnology. in the mycobacterium tuberculosis reca mini-mini intein (δδihh), a single valine to leucine substitution at position 67 (v67l) dramatically increases intein stability and activity. however, crystal structures show that the v67l mutation causes minimal structural rearrangements, with a root-mean-square deviation of 0.2 å between δδihh-v67 and δδihh-l67. thus, the structural mechanisms fo ...201728488863
involvement of the warburg effect in non-tumor diseases processes.warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. interestingly, increasing researchers show that warburg effect plays a crucial role in non-tumor diseases. for instance, inhibition of warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (ph). interference of warburg effect improves mitochondrial function and cardiac function in the process of cardiac hyper ...201728488732
abdominopelvic tuberculosis with a frozen section analysis consistent with ovarian cancer.pelvic tuberculosis is a type of extrapulmonary tuberculosis. the disease is accompanied by clinical and laboratory findings which may be unspecific and present aspects of other diseases, including gynecological malignancies. in this report, the authors presented a case of pelvic tuberculosis associated with peritoneal tuberculosis in a young woman exhibiting imaging and tumor markers consistent with ovarian neoplasm. an intraoperative frozen section analysis detected atypical cells that were su ...201728487789
regulatory t cells and pro-inflammatory responses predominate in children with tuberculosis.following infection with mycobacterium tuberculosis (m.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. the exact mechanisms required for containment of m.tb are not known, but would be important to identify correlates of protection.201728487695
new insights in to the intrinsic and acquired drug resistance mechanisms in mycobacteria.infectious diseases caused by clinically important mycobacteria continue to be an important public health problem worldwide primarily due to emergence of drug resistance crisis. in recent years, the control of tuberculosis (tb), the disease caused by mycobacterium tuberculosis (mtb), is hampered by the emergence of multidrug resistance (mdr), defined as resistance to at least isoniazid (inh) and rifampicin (rif), two key drugs in the treatment of the disease. despite the availability of curative ...201728487675
digitally barcoding mycobacterium tuberculosis reveals in vivo infection dynamics in the macaque model of tuberculosis.infection with mycobacterium tuberculosis causes a spectrum of outcomes; the majority of individuals contain but do not eliminate the infection, while a small subset present with primary active tuberculosis (tb) disease. this variability in infection outcomes is recapitulated at the granuloma level within each host, such that some sites of infection can be fully cleared while others progress. understanding the spectrum of tb outcomes requires new tools to deconstruct the mechanisms underlying di ...201728487426
performance of mycobacterium growth indicator tube bactec 960 with lowenstein-jensen method for diagnosis of mycobacterium tuberculosis at ethiopian national tuberculosis reference laboratory, addis ababa, ethiopia.bacteriological confirmed active case detection remains the corner stone for diagnosing tuberculosis. non-radiometric liquid culture system mycobacterium growth indicator tube with automated interface had been recommended by expert groups in addition to conventional solid culture media such as lowenstein-jensen. however in high burden resource limited countries advanced non-radiometric based tuberculosis diagnostic methods such as mgit 960 is limited. therefore we have evaluated the performance ...201728486950
ileocaecal and transverse colonic tuberculosis mimicking colonic malignancy - a case report.gastrointestinal tuberculosis is common in the developing world especially in the lower socioeconomic groups. in elderly, it may mimic malignancy.201728486175
mechanistic principles behind molecular mechanism of rifampicin resistance in mutant rna polymerase beta subunit of mycobacterium tuberculosis.evolution of drug-resistant mycobacterium strains threatens the tb treatment and control programs globally. rifampicin (rif) is an important first line antitubercular drug. resistance to rifampicin is caused mainly by mutations in its target rna polymerase beta subunit protein (rpob). rpob contains a rifampicin resistance determining region (rrdr) and has several potent sites for mutations. in this study, we have investigated mutations of a single site (h451) to eight different amino acids, invo ...201728485504
impact of pe_pgrs33 gene polymorphisms on mycobacterium tuberculosis infection and pathogenesis.pe_pgrs33 is a surface-exposed protein of mycobacterium tuberculosis (mtb) which exerts its role in macrophages entry and immunomodulation. in this study, we aimed to investigate the polymorphisms in the pe_pgrs33 gene of mtb clinical isolates and evaluate their impact on protein functions. we sequenced pe_pgrs33 in a collection of 135 clinical strains, genotyped by 15-loci miru-vntr and spoligotyping and belonging to the mtb complex (mtbc). overall, an association between pe_pgrs33 alleles and ...201728484686
in-depth characterization and functional analysis of clonal variants in a mycobacterium tuberculosis strain prone to microevolution.the role of clonal complexity has gradually been accepted in infection by mycobacterium tuberculosis (mtb), although analyses of this issue are limited. we performed an in-depth study of a case of recurrent mtb infection by integrating genotyping, whole genome sequencing, analysis of gene expression and infectivity in in vitro and in vivo models. four different clonal variants were identified from independent intrapatient evolutionary branches. one of the single-nucleotide polymorphisms in the v ...201728484440
tuberculosis in migrants in low-incidence countries: epidemiology and intervention entry points.as tuberculosis (tb) rates continue to decline in native populations in most low tb incidence countries, the proportion of tb patients born outside their country of residence ('foreign-born') increases. some low-incidence countries have experienced a substantial increase in tb rates related to recent increases in the number of asylum seekers and other migrants from tb-endemic countries. however, average tb rates among the foreign-born in low-incidence countries declined moderately in 2009-2015. ...201728482956
risk and impact of tuberculosis in patients with multiple myeloma.we investigated the risk and impact of mycobacterium tuberculosis (tb) infection in patients with multiple myeloma (mm). we identified 3979 mm patients from taiwan's national health insurance database between 2000 and 2011 and compared the incidence rates of tb infection in these patients with 15,916 randomly selected age-, sex-, and comorbidity-matched subjects without mm. the risk of tb was higher in the myeloma cohort (adjusted hazard ratio [hr] 3.11, 95% confidence interval [ci] 2.41-4.02). ...201728482714
[molecular epidemiologic study on mycobacterium tuberculosis from drug resistance monitoring sites of guangdong province, 2015].objective: to understand the characteristics of mycobacterium tuberculosis (mtb) in epidemiology and distribution from guangdong province, and to explore the risk factors associated with drug resistance. methods: a total of 225 clinical strains of mtb collected from 5 drug resistance monitoring sites of guangdong province in 2015 were tested by regions of difference 105 (rd105) deletion test and 15 loci mycobacterial interspersed repetitive units (miru) were used for genotyping. gene clustering ...201728482417
new drugs for the treatment of mycobacterium tuberculosis infection.tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. following the breakthrough of first-line anti-tb medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. in order to address this issue, several novel possible candidates for tuberculosis therapy have ...201728482292
cmr is a redox-responsive regulator of dosr that contributes to m. tuberculosis virulence.mycobacterium tuberculosis (mtb) is the causative agent of pulmonary tuberculosis (tb). mtb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. transcriptional reprogramming is essential for tb pathogenesis. in vitro, cmr (a member of the crp/fnr super-family of transcription regulators) bound at a single dna site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. transcriptional pr ...201728482027
mycobacterium tuberculosis: what is the role of ppe2 during infection? 201728481123
interleukin-37: a new molecular target for host-directed therapy of tuberculosis. 201728481119
hydrogen/deuterium exchange mass spectrometry reveals mechanistic details of activation of nucleoside diphosphate kinases by oligomerization.most oligomeric proteins become active only after assembly, but why oligomerization is required to support function is not well understood. here, we address this question using the wild type (wt) and a destabilized mutant (d93n) of the hexameric nucleoside diphosphate kinase from the pathogen mycobacterium tuberculosis (mt-ndpk). the conformational dynamics and oligomeric states of each were analyzed during unfolding and/or folding by hydrogen/deuterium exchange mass spectrometry (hdx-ms) at pep ...201728481113
differential flap dynamics in l,d-transpeptidase2 from mycobacterium tuberculosis revealed by molecular dynamics.despite the advances in tuberculosis treatment, tb is still one the most deadly infectious diseases and remains a major global health quandary. mycobacterium tuberculosis (mtb) is the only known mycobacterium with a high content of 3→3 crosslinks in the biosynthesis of peptidoglycan, which is negligible in most bacterial species. an mtb lacking ldtmt2 leads to alteration of the colony morphology and loss of virulence which makes this enzyme an attractive target. regardless of the vital role of l ...201728480928
nanoemulsion for the effective treatment and management of anti-tubercular drug therapy.tuberculosis is considered as one of the deadliest diseases of human existence. since ancient age the treatment of tuberculosis has been highly challenging primarily owing to the pathogenic nature of the mycobacterium and its diverse spots of localization in human body including lungs, liver, spleen, eye, meninges and lymph nodes.201728480833
the rate of drug-resistant tuberculosis in korean children and adolescents since 2007.the incidence of drug-resistant tuberculosis (dr-tb) in pediatric populations is a critical indicator of national tb management and treatment strategies. limited data exist regarding the rate of pediatric dr-tb. in this study, we aimed to analyze the status of dr-tb in korean children from 2007 to 2013. we analyzed specimens submitted to the korean institute of tuberculosis using mycobacterium tuberculosis culture and drug susceptibility tests (dsts) from january 2007 through december 2013. spec ...201728480653
analysis of rrs gene mutations in amikacin resistant clinical isolates of mycobacterium tuberculosis from khyber pakhtunkhwa, pakistan.tuberculosis is a major infectious disease caused by mycobacterium tuberculosis complex. antimicrobial drugs are used to control tb infections. molecular mechanisms controlling resistance to second-line drugs are not completely understood and no endogenous information is available regarding these mechanisms. the present study reports mutational analysis of rrs gene in mycobacterium tuberculosis isolates collected from khyber pakhtunkhwa province of pakistan. a total of 499 mycobacterium tubercul ...201728479509
prokaryotic ubiquitin-like protein and its ligase/deligase enyzmes.prokaryotic ubiquitin-like protein (pup) and the modification enzymes involved in attaching pup to or removing it from target proteins present a fascinating example of convergent evolution with respect to eukaryotic ubiquitination. like ubiquitin (ub), pup is a small protein that can be covalently attached to lysine side chains of cellular proteins, and like ub, it can serve to recruit tagged proteins for proteasomal degradation. however, unlike ub, pup is conformationally highly dynamic, exhibi ...201728478282
"the impact of mycobacterium tuberculosis immune evasion on protective immunity: implications for tb vaccine design" - meeting report.tuberculosis (tb) is the major cause of death from infectious diseases around the world, particularly in hiv infected individuals. tb vaccine design and development have been focused on improving bacille calmette-guérin (bcg) and evaluating recombinant and viral vector expressed mycobacterium tuberculosis (mtb) proteins, for boosting bcg-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of bcg in protecting against infection or disease. o ...201728476627
a phenotypic based target screening approach delivers new antitubercular ctp synthetase inhibitors.despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. however, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. in this context, the newly validated drug target ctp synthetase pyrg was exploited to assess a target-based approach of already known, but untargeted, antim ...201728475832
impact of fluoroquinolone use on mortality among a cohort of suspected drug-resistant tuberculosis patients.previous retrospective and in vitro studies suggest that use of later generation fluoroquinolones may reduce mortality risk and improve treatment outcomes for drug-resistant tuberculosis patients, including individuals resistant to a fluoroquinolone. meta-analysis results are mixed and few studies have examined this relationship prospectively.201728475735
mhc ib molecule qa-1 presents mycobacterium tuberculosis peptide antigens to cd8+ t cells and contributes to protection against infection.a number of nonclassical mhc ib molecules recognizing distinct microbial antigens have been implicated in the immune response to mycobacterium tuberculosis (mtb). hla-e has been identified to present numerous mtb peptides to cd8+ t cells, with multiple hla-e-restricted cytotoxic t lymphocyte (ctl) and regulatory t cell lines isolated from patients with active and latent tuberculosis (tb). in other disease models, hla-e and its mouse homolog qa-1 can act as antigen presenting molecules as well as ...201728475642
first-time detection and identification of the mycobacterium tuberculosis complex members in extrapulmonary tuberculosis clinical samples in south tunisia by a single tube tetraplex real-time pcr assay.tunisia has one of the highest burdens of extrapulmonary tuberculosis (eptb) among tuberculosis (tb) cases but the contribution of mtbc-mediated human eptb is unknown. eptb diagnosis is challenging due to the paucibacillary nature of clinical samples. therefore, a need of a simplified molecular method for sensitive and specific tb detection and differentiation of mtbc members caused eptb remains a priority to an early diagnosis, optimize successful anti-tb treatment and minimize transmission. we ...201728475618
correction: intracellular growth of mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells. 201728475039
risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.mycobacterium tuberculosis (tb) is one of the world's most devastating public health threats. our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (nsaids) affect the risk of new incident active tb disease.201728472944
type-ii nadh dehydrogenase (ndh-2): a promising therapeutic target for antitubercular and antibacterial drug discovery.tuberculosis (tb) is highly dangerous due to the development of resistance to first-line drugs. moreover, mycobacterium tuberculosis (mtb) has also developed resistance to newly approved antitubercular drug bedaquiline. this necessitates the search for drugs acting on newer molecular targets. the energy metabolism of mycobacteria is the prime focus for the discovery of novel antitubercular drugs. targeting type-2 nadh dehydrogenase (ndh-2) involved in the production of respiratory atp could, the ...201728472892
clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis regimen.drug-resistant tuberculous meningitis (tbm) is difficult to diagnose and treat. mortality is high and optimal treatment is unknown. we compared clinical outcomes of drug-resistant and -susceptible tbm treated with either standard or intensified antituberculosis treatment.201728472255
copy number variation of fcgr genes in etiopathogenesis of sarcoidosis.we have previously revealed that, in contrast to polymorphism of fcgr2b and fcgr3b, polymorphism of fcgr2a, fcgr2c and fcgr3a genes, encoding receptors for fc fragment of immunoglobulin g (fcγ receptors), play a role in increased level of circulating immune complexes with occurrence of mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis. however, this immunocomplexemia might also be caused by decreased clearance by immune cells due to a changed copy number of fcgr genes. ...201728472129
performance of taqman array card to detect tb drug resistance on direct specimens.culture based phenotypic drug susceptibility testing (dst) for mycobacterium tuberculosis (tb) is time consuming therefore rapid genotypic methods are increasingly being utilized. we previously developed and evaluated on tb isolates a rapid genotypic taqman array card (tac) that detects mutations in several resistance-associated genes using dozens of primer pairs, probes, and high resolution melt analysis, with >96% accuracy versus sanger sequencing. in this study we examined the performance of ...201728472124
transcription factor rv0081 from mycobacterium tuberculosis: purification, crystallization and initial crystallographic analysis.because of its high infectivity and pathogenicity, mycobacterium tuberculosis is a serious threat to human health. while the transcription-regulatory system of m. tuberculosis remains incompletely understood, rv0081, an essential regulatory hub, is known to mediate the initial response to hypoxia in the long-term survival of m. tuberculosis. here, the production, crystallization and initial x-ray crystallographic analysis of rv0081 are reported. the crystals of rv0081 belonged to space group p62 ...201728471360
mycobacterium tuberculosis found at both skin lesions and mantoux testing site in a patient with erythema induratum of bazin.mycobacterium tuberculosis is very rarely found in erythema induratum of bazin; recently, we found an unusual case with positive acid-fast bacilli and polymerase chain reaction for detecting m. tuberculosis in both skin lesions of the extremities and the site of mantoux test.201728470727
novel adjuvant for immunization against tuberculosis: dna vaccine expressing mycobacterium tuberculosis antigen 85a and interleukin-15 fusion product elicits strong immune responses in mice.to investigate the potential of interleukin (il)-15 as a novel adjuvant for mycobacterium tuberculosis (mtb) antigen 85a (ag85a) vaccine.201728470626
clinical impact of nucleic acid amplification testing in the diagnosis of mycobacterium tuberculosis: a 10-year longitudinal study.nucleic acid amplification (naa) testing for mycobacterium tuberculosis (mtb) offers improved diagnostic accuracy, compared with smear microscopy, in differentiating mtb from other mycobacteria. we aimed to evaluate the reliability and projected impact of naa testing in patients with acid-fast bacilli (afb) smear-positive respiratory samples.201728470022
crystal structure of the essential biotin-dependent carboxylase acca3 from mycobacterium tuberculosis.biotin-dependent acetyl-coa carboxylases catalyze the committed step in type ii fatty acid biosynthesis, the main route for production of membrane phospholipids in bacteria, and are considered a key target for antibacterial drug discovery. here we describe the first structure of acca3, an essential component of the acetyl-coa carboxylase system in mycobacterium tuberculosis (mtb). the structure, sequence comparisons, and modeling of ligand-bound states reveal that the atp cosubstrate-binding sit ...201728469974
a chest wall mass after breast carcinoma surgery: a simple diagnosis?tuberculosis affects pulmonary and extra-pulmonary sites with a multitude of differing presentations. the involvement of thoracic wall is a rare entity. we report the case of a patient who had a tumefaction on the right chest wall 6 months after a right breast mastectomy. after an initial radiological suspicion of malignancy, we detected intraoperatively an abscess in which histologic examination revealed granulomas with multinucleated giant cells.201728469918
construction and analysis of the transcription factor-microrna co-regulatory network response to mycobacterium tuberculosis: a view from the blood.mycobacterium tuberculosis (mtb) infection has been regional outbreak, recently. the traditional focus on the patterns of "reductionism" which was associated with single molecular changes has been unable to meet the demand of early diagnosis and clinical application when current tuberculosis infection happened. in this study, we employed a systems biology approach to collect large microarray data sets including mrnas and micrornas (mirnas) to identify the differentially expressed mrnas and mirna ...201728469803
lineage-specific snps for genotyping of mycobacterium tuberculosis clinical isolates.tuberculosis (tb) is a severe infectious disease worldwide. genetic variation of the causative agent, mycobacterium tuberculosis (mtb), determines the outcomes of infection and anti-tb treatment. until recently, there has been no effective and convenient way for classifying clinical isolates based on the dna sequences of the divergent lineages of mtb infecting human populations. here, we identified single nucleotide polymorphisms (snps) of six representative strains from taiwan by whole-genome s ...201728469152
pyopericardium with cardiac tamponade in a nigerian child with acute osteomyelitis.in pyopericardium, pus accumulates in the pericardial space as a result of infection by pyogenic organisms, most common of which are staphylococcus aureus and mycobacterium tuberculosis. these patients are at risk of cardiac tamponade. apart from pericardiocentesis in the management of these patients, definitive drug treatment may pose a formidable challenge in a setting of coinfection as in patients with tuberculosis who are predisposed to secondary bacterial infections. this was the case of ou ...201728465998
endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron.the iron-regulatory hormone hepcidin is induced early in infection, causing iron sequestration in macrophages and decreased plasma iron; this is proposed to limit the replication of extracellular microbes, but could also promote infection with macrophage-tropic pathogens. the mechanisms by which hepcidin and hypoferremia modulate host defense, and the spectrum of microbes affected, are poorly understood. using mouse models, we show that hepcidin was selectively protective against siderophilic ex ...201728465342
transcription facilitated genome-wide recruitment of topoisomerase i and dna gyrase.movement of the transcription machinery along a template alters dna topology resulting in the accumulation of supercoils in dna. the positive supercoils generated ahead of transcribing rna polymerase (rnap) and the negative supercoils accumulating behind impose severe topological constraints impeding transcription process. previous studies have implied the role of topoisomerases in the removal of torsional stress and the maintenance of template topology but the in vivo interaction of functionall ...201728463980
novel copper(ii) complexes with hydrazides and heterocyclic bases: synthesis, structure and biological studies.five new copper(ii) complexes of the type [cu(no)(nn)(clo4)2], in which no=4-fluorophenoxyacetic acid hydrazide (4-fh) or 4-nitrobenzoic hydrazide (4-nh) and nn=1,10-phenanthroline (phen), 4-4'-dimethoxy-2-2'-bipyridine (dmb) or 2,2-bipyridine (bipy) were synthesized and characterized using various spectroscopic methods. the x-ray structural analysis of one representative compound indicates that the geometry around the copper ion is distorted octahedron, in which the ion is coordinated to hydraz ...201728463762
early detection of the growth of mycobacterium tuberculosis using magnetophoretic immunoassay in liquid culture.tuberculosis (tb) is an often neglected, epidemic disease that remains to be controlled by contemporary techniques of medicine and biotechnology. in this study, a nanoscale sensing system, referred to as magnetophoretic immunoassay (mpi) was designed to capture culture filtrate protein (cfp)-10 antigens effectively using two different types of nanoparticles (nps). two specific monoclonal antibodies against cfp-10 antigen were used, including gold nps for signaling and magnetic particles for sepa ...201728463738
a functional toll-interacting protein variant is associated with bacillus calmette-guérin-specific immune responses and tuberculosis.the molecular mechanisms that regulate tuberculosis susceptibility and bacillus calmette-guérin (bcg)-induced immunity are mostly unknown. however, induction of the adaptive immune response is a critical step in host control of mycobacterium tuberculosis. toll-interacting protein (tollip) is a ubiquitin-binding protein that regulates innate immune responses, including toll-like receptor signaling, which initiate adaptive immunity. tollip variation is associated with susceptibility to tuberculosi ...201728463648
6-nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases.as part of a quest for backups to the antitubercular drug pretomanid (pa-824), we investigated the unexplored 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]-thiazoles and related -oxazoles. the nitroimidazothiazoles were prepared in high yield from 2-bromo-4-nitroimidazole via heating with substituted thiiranes and diisopropylethylamine. equivalent examples of these two structural classes provided broadly comparable mics, with 2-methyl substitution and extended aryloxymethyl side chains preferred; albei ...201728462832
building a full-atom model of l,dtranspeptidase 2 from mycobacterium tuberculosis for screening new inhibitors.l,d-transpeptidase 2 from mycobacterium tuberculosis plays a key role in the formation of the cell wall of a pathogen and catalyzes the cross-linking of growing peptidoglycan chains by non-classical 3-3 bonds, which causes resistance to a broad spectrum of penicillins. molecular modeling of enzyme interactions with the n- and c-terminal tetrapeptide fragments of growing peptidoglycan chains has been performed for the first time and has allowed us to highlight the peculiarities of their binding a ...201728461973
proteomics for the investigation of mycobacteria.the physiology of mycobacterium tuberculosis, the causative agent of tuberculosis, is being studied with intensity. however, despite the genomic and transcriptomic data available today, the pathogenic potential of these bacteria remains poorly understood. therefore, proteomic approaches seem relevant in studying mycobacteria. this review covers the main stages in the proteomic analysis methods used to study mycobacteria. the main achievements in the area of m. tuberculosis proteomics are describ ...201728461970
effect of tuberculosis treatment on leptin levels, weight gain, and percentage body fat in indonesian children.tuberculosis (tb) remains a problem in the community. tb patients usually experience malnutrition, which is characterized by both decreased body weight (bw) and body fat percentage (bfp). leptin, an important regulator of bw, also plays an important role in cellular immunity, which is integral to defense against mycobacterium tuberculosis infection. we analyzed the effect of an anti-tb treatment regimen on the leptin level, bw, and bfp of children with tb.201728461825
modulation of mycobacterium tuberculosis-specific humoral immune responses is associated with strongyloides stercoralis co-infection.helminth infections are known to influence t cell responses in latent tuberculosis (ltbi). whether helminth infections also modulate b cell responses in helminth-tuberculosis co-infection is not known.201728459817
peripancreatic tuberculous lymphadenitis diagnosed via endoscopic ultrasound-guided fine-needle aspiration and polymerase chain reaction.we performed endoscopic ultrasound-guided fine-needle aspiration (eus-fna) on a patient presenting with an asymptomatic peripancreatic mass-like lesion. the aspiration cytologic finding was class ii. on positron emission tomography-computed tomography (pet-ct), there were hot spots in the left supra-clavicular lymph node and the peripancreatic lesion. a whole biopsy of the left supra-clavicular lymph node revealed tuberculous lymphadenitis. polymerase chain reaction (pcr) using tissue obtained v ...201728458310
targeting isocitrate lyase for the treatment of latent tuberculosis.tuberculosis (tb) is an infectious disease caused by mycobacterium tuberculosis that can remain dormant for many years before becoming active. one way to control and eliminate tb is the identification and treatment of latent tb, preventing infected individuals from developing active tb and thus eliminating the subsequent spread of the disease. isocitrate lyase (icl) is involved in the mycobacterial glyoxylate and methylisocitrate cycles. icl is important for the growth and survival of m. tubercu ...201728458043
mycobacterium tuberculosis infection at pacemaker implantation site.expanding clinical indications of cardiac rhythm management have led to an increased use of pacemaker implantation which is associated with increased incidence of pacemaker infections. staphylococcus aureus and epidermidis account for the majority of pacemaker infections. infection of implantable cardiac devices by mycobacterium species, particularly mycobacterial tuberculosis is rare. we present a case of delayed pacemaker pocket infection with tuberculosis and review of literature of pacemaker ...201728457043
qsar based therapeutic management of m. tuberculosis.mycobacterium tuberculosis is responsible for severe mortality and morbidity worldwide but, under-developed and developing countries are more prone to infection. in search of effective and wide-spectrum anti-tubercular agents, interdisciplinary approaches are being explored. of the several approaches used, computer based quantitative structure activity relationship (qsar) have gained momentum. structure-based drug design and discovery implies a combined knowledge of accurate prediction of ligand ...201728456911
positive epistasis of major low-cost drug resistance mutations rpob531-ttg and katg315-acc depends on the phylogenetic background of mycobacterium tuberculosis strains.mycobacterium tuberculosis beijing genotype strains increasingly circulate in different world regions, either as historical endemic, e.g. in east asia, or recently imported, e.g. in south america, and this family is regarded as the most successful lineage of the global tuberculosis (tb) epidemic. here we analysed the transmission capacity of these strains in the context of their phylogenetic background and drug resistance mutations. the study collection included all multidrug resistant (mdr) str ...201728456705
selection and identification of specific glycoproteins and glycan biomarkers of macrophages involved in mycobacterium tuberculosis infection.macrophages are the primary host target cells of mycobacterium tuberculosis (m.tb). however, little is known about the changes of membrane glycopatterns of macrophages in response to m. tb infection. using lectin microarrays we compared the differential expression of glycopatterns of macrophages upon stimulation with the heat-inactivated virulent m.tb h37rv or attenuate m.tb h37ra. we found that widespread alteration of macrophage membrane glycopatterns were induced by the heat-inactivated virul ...201728454656
the diacylglycerol acyltransferase rv3371 of mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations.triacylglycerol (tag) is important to mycobacteria both as cell envelope component and energy reservoir. mycobacterium tuberculosis (mtb) genome encodes at least 15 putative tag synthase (tgs)s. we report that one of these genes, rv3371, specific to pathogenic mycobacteria, when expressed in m. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated tag levels. rv3371 was found to largely localize in the cell membrane. the rv3371 promot ...201728454654
strains of mycobacterium tuberculosis transmitting infection in brazilian households and those associated with community transmission of tuberculosis.molecular epidemiologic studies have shown that the dynamics of tuberculosis transmission varies geographically. we sought to determine which strains of mycobacterium tuberculosis (mtb) were infecting household contacts (hhc), and which were causing clusters of tuberculosis (tb) disease in vitoria-es, brazil. a total of 741 households contacts (445 tst +) and 139 index cases were characterized according to the proportion of contacts in each household that had a tuberculin skin test positive: low ...201728454653
selection, characterization, and application of dna aptamers for detection of mycobacterium tuberculosis secreted protein mpt64.rapid detection of mycobacterium tuberculosis (mtb), an etiological agent of tuberculosis (tb), is important for global control of this disease. aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. the aim of the current study was to select and characterize single-stranded dna aptamers against mpt64 protein, one of the predominant secreted proteins of mtb pathogen. aptamers specific to mpt64 protein were sele ...201728454652
clinical evaluation of the abbott realtime mtb assay for direct detection of mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.rapid and reliable diagnosis is crucial for correct management of tuberculosis. the abbott realtime mtb assay represents a novel qualitative real-time pcr assay for direct detection of m. tuberculosis-complex (mtb) dna from respiratory samples. the test targets two highly conserved sequences, the multi-copy insertion element is6110 and the protein antigen b (pab) gene of mtb, allowing even the detection of is6610-deficient strains. we evaluated this commercial diagnostic test by analyzing 200 re ...201728454651
the siglec14 null allele is associated with mycobacterium tuberculosis- and bcg-induced clinical and immunologic outcomes.humans exposed to mycobacterium tuberculosis (mtb) have variable susceptibility to tuberculosis (tb) and its outcomes. siglec-5 and siglec-14 are members of the sialic-acid binding lectin family that regulate immune responses to pathogens through inhibitory (siglec-5) and activating (siglec-14) domains. the siglec14 coding sequence is deleted in a high proportion of individuals, placing a siglec5-like gene under the expression of the siglec14 promoter (the siglec14 null allele) and causing expre ...201728454648
activity of rifampicin and linezolid combination in mycobacterium tuberculosis.linezolid (lzd) is not commonly used for treating tuberculosis (tb), but in some patients with drug-resistant tb it is being used. however, the in vitro lzd activity, in combination with rifampicin (rif) against mycobacterium tuberculosis has not been fully elucidated.201728454646
revisiting the hunter gaston discriminatory index: note of caution and courses of change.hunter gaston discriminatory index (hgdi) is a widely used estimator of discriminatory power of genotyping methods and diversity of molecular markers in bacterial pathogens, including mycobacterium tuberculosis. in my opinion, the index is somewhat misleading: a closer look at common practice and particular studies reveals that values in the range of 0.6-0.9 are modest but uncritically perceived as high. i propose and discuss three courses of change: (i) to continue using hgdi but be aware of th ...201728454645
genetic diversity of immune-related antigens in region of difference 2 of mycobacterium tuberculosis strains.region of difference 2 (rd2) was lost during the ongoing propagation of bcg between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. some data demonstrate that rd2 plays a role in mycobacterial virulence, and that its deletion from mycobacterium tuberculosis leads to a decrease in bacterial growth in both a macrophage and a murine model. human t-cell epitopes of m. tuberculosis are evolutionarily hyperconserved and thus it was deduced that m. tuberculo ...201728454644
multi-subunit bcg booster vaccine gamtbvac: assessment of immunogenicity and protective efficacy in murine and guinea pig tb models.new innovative vaccines are highly needed to combat the global threat posed by tuberculosis. efficient components-antigens and adjuvants-are crucial for development of modern recombinant tb vaccines. this study describes a new vaccine (gamtbvac) consisting of two mycobacterial antigen fusions (ag85a and esat6-cfp10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of deae-dextran core, and with cpg oligodeoxynucleotides (tlr9 agonists). gamtbvac and its co ...201728453555
expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors.the global incidence of tuberculosis is increasing at an alarming rate, and mycobacterium tuberculosis (mtb) is the causative agent for tuberculosis, a disease with high mortality. lipoarabinomannan (lam) is one of the major components of the mtb cellular envelope and is an attractive scaffold for developing anti-tubercular drugs, vaccines and diagnostics. herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time. the arabinomannan synthe ...201728451321
fundus findings in a series of patients with extrapulmonary tuberculosis in thailand.the aim of this study was to determine the frequency of fundus abnormalities among patients who are undergoing or have recently completed treatment for extrapulmonary tuberculosis (etb).201728450377
system for efficacy and cytotoxicity screening of inhibitors targeting intracellular mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis (tb), is a leading cause of morbidity and mortality worldwide. with the increased spread of multi drug-resistant tb (mdr-tb), there is a real urgency to develop new therapeutic strategies against m. tuberculosis infections. traditionally, compounds are evaluated based on their antibacterial activity under in vitro growth conditions in broth; however, results are often misleading for intracellular pathogens like m. tuberculosis since ...201728448028
mitigation of discordant rifampicin-susceptibility results obtained by xpert mycobacterium tuberculosis/rifampicin and mycobacterium growth indicator tube.simultaneous use of genotypic and phenotypic diagnostic tools for detection of rifampicin (rif) susceptibility may yield discrepant results.201728447869
mtbvac from discovery to clinical trials in tuberculosis-endemic countries.bcg remains the only vaccine against tuberculosis (tb) in use today and despite its impressive global coverage, the nature of bcg protection against the pulmonary forms of tb remains subject to ongoing debate. because of the limitations of bcg, novel tb vaccine candidates have been developed and several have reached the clinical pipeline. one of these candidates is mtbvac, the first and only tb vaccine in the clinical pipeline to date based on live-attenuated mycobacterium tuberculosis that has ...201728447476
structural investigations on orotate phosphoribosyltransferase from mycobacterium tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis.the mycobacterium tuberculosis orotate phosphoribosyltransferase (mtoprt) catalyses the conversion of α-d-5-phosphoribosyl-1-pyrophosphate (prpp) and orotate (oa) in pyrophosphate and orotidine 5'-monophosphate (omp), in presence of mg(2+). this enzyme is the only responsible for the synthesis of orotidine 5'-monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway, making mtoprt an attractive drug target for the development of antitubercular agents. we report the crystal st ...201728446777
use of genexpert remnants for drug resistance profiling and molecular epidemiology of tuberculosis in libreville, gabon.multidrug-resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis pose major problems for global health. the genexpert mtb/rif (xpert) assay rapidly detects resistance to rifampin (rif(r)), but for detection of the additional resistance that defines mdr-tb (mdr tuberculosis) and xdr-tb, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. we sought to determine whether the remnants of sputa prepared for the xper ...201728446574
distinct prevalence of drug-resistant tuberculosis in gansu, china: a retrospective study on drug susceptibility profiles between 2010 and 2014.limited knowledge is available on regional distribution of antituberculosis (tb) drug resistance and on province-specific time-trends in tb drug susceptibility in china. to obtain the latest information about the dynamics of drug-resistant tb in gansu province, we conducted a retrospective study and analyzed data on drug resistance among new tb cases diagnosed between june 2010 and may 2014 in gansu, china. the data were collected from the only tb surveillance and treatment hospital in gansu and ...201728445109
current approaches and future prospects of nanomedicines in tuberculosis therapy.tuberculosis (tb), which is caused by the mycobacterium tuberculosis, is a serious threat and one of the major health problems worldwide. in recent years, an estimated of 9.6 million tb cases occurred and 1.5 million death occurred due to tb worldwide. the present review is an attempt to introduce this disease focusing on the pathophysiology of the disease, the current approachesand the related patents for treatment and the future planningfor combating this disease.201728443511
evaluation of a new ifn-γ release assay for rapid diagnosis of active tuberculosis in a high-incidence setting.blood-based interferon-gamma (ifn-γ) release assays (igras) have been proven to be useful in the diagnosis of mycobacterium tuberculosis (mtb) infection. however, igras have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. the established t-spot. tb assay containing mtb-specific antigens esat-6 and cfp10 are widely used for immunodiagonsis of mtb infection, but the high cost is one of the restricting ...201728443247
estimating tuberculin skin test reactions among children and teenagers who received the bacillus calmette-guerin vaccination at birth: a meta-analysis.tuberculin skin reaction size is one indicator of bacillus calmette-guérin (bcg) vaccine efficacy and a way to diagnose latent infection. several primary studies have examined this issue. combining the results of these studies using a meta-analysis will provide reliable evidence regarding this indicator for policymakers. this study aimed to estimate the total frequency of different tuberculin skin test reactions among iranian children and teenagers who received the bcg vaccination at birth.201728443219
the exit strategy: an approach for identifying bacterial proteins exported during host infection.exported proteins of bacterial pathogens function both in essential physiological processes and in virulence. past efforts to identify exported proteins were limited by the use of bacteria growing under laboratory (in vitro) conditions. thus, exported proteins that are exported only or preferentially in the context of infection may be overlooked. to solve this problem, we developed a genome-wide method, named exit (exported in vivotechnology), to identify proteins that are exported by bacteria d ...201728442606
complex multifractal nature in mycobacterium tuberculosis genome.the mutifractal and long range correlation (c(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. in this study c(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria mycobacterium tuberculosis. genomic sequences of m. tuberculosis isolates displayed significant variations in c(r) and f(α) reflecting inherent differences in sequences among iso ...201728440326
latently and uninfected healthcare workers exposed to tb make protective antibodies against mycobacterium tuberculosis.the role of igs in natural protection against infection by mycobacterium tuberculosis (mtb), the causative agent of tb, is controversial. although passive immunization with mabs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in b cell-depleted animals only showed modest phenotypes. we do not know if humans make protective antibody responses. here, we investigated whether healthcare workers in a beijing tb hospital-who, although expos ...201728438994
pyrazinoic acid inhibits a bifunctional enzyme in mycobacterium tuberculosis.pyrazinamide (pza), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. while the mechanism of activation of this prodrug into pyrazinoic acid (poa) by mycobacterium tuberculosis has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. here, we report how a new pza resistance determinant, the asp67asn substitution in rv2783, confers m. tuberculosis resistance to pza. expression of th ...201728438933
effects on the qt interval of a gatifloxacin-containing regimen versus standard treatment of pulmonary tuberculosis.the effects on ventricular repolarization-recorded on the electrocardiogram (ecg) as lengthening of the qt interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. a correction factor (qtc) is introduced to make the qt independent of the heart rate, translating into the slope of the regression line between qt and heart rate being close to zero. ecgs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) ...201728438924
convenient pcr method for variable-number tandem-repeat typing of mycobacterium tuberculosis clinical isolates.variable-number tandem-repeat typing for mycobacterium tuberculosis clinical isolates contributes to evidence-based tuberculosis control. however, cumbersome pcr procedures for the typing have disturbed routine analyses. we proposed a convenient pcr method for the typing using a pcr master mix that provides rapidity and long-term stability of the frozen pcr cocktail.201728438643
isolated splenic tuberculosis with subsequent paradoxical deterioration: a case report.isolated tuberculosis of the spleen has been described occasionally in literature, mostly in immunosuppressed individuals with various risk factors. sequestration in the spleen makes such mycobacterium tuberculosis infection difficult to diagnose. this report describes an extremely rare case of isolated splenic tuberculosis in an immunocompetent individual.201728438221
early detection of multidrug- and pre-extensively drug-resistant tuberculosis from smear-positive sputum by direct sequencing.emergence of multidrug- and extensively drug-resistant tuberculosis (m/xdr-tb) is a major hurdle for tb control programs especially in developing countries like china. resistance to fluoroquinolones is high among mdr-tb patients. early diagnosis of mdr/pre-xdr-tb is essential for lowering transmission of drug-resistant tb and adjusting the treatment regimen.201728438132
reproducibility of african giant pouched rats detecting mycobacterium tuberculosis.african pouched rats sniffing sputum samples provided by local clinics have significantly increased tuberculosis case findings in tanzania and mozambique. the objective of this study was to determine the reproducibility of rat results.201728438117
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