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cholesterol metabolism: a potential therapeutic target in mycobacteria.tuberculosis (tb), although a curable disease, is still one of the most difficult infections to treat. mycobacterium tuberculosis infects 10 million people worldwide and kills 1.5 million people each year. reactivation of a latent infection is the major cause of tb. cholesterol is a critical carbon source during latent infection. catabolism of cholesterol contributes to the pool of propionyl-coa, a precursor that is incorporated into lipid virulence factors. the m. tuberculosis genome contains a ...201628002883
mycobacterium tuberculosis cell wall released fragments by the action of the human lung mucosa modulate macrophages to control infection in an il-10-dependent manner.mycobacterium tuberculosis (m.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. during infection, m.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (alf), an environment that m.tb encounters at different stages of the infection and disease. alf is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. here we demonstrate that alf hydrolases, at t ...201628000679
active tuberculosis patients have high levels of iga anti-alpha-crystallin and isocitrate lyase proteins.mexico city, mexico.201628000588
evaluation of omnigene®•sputum-stabilised sputum for long-term transport and xpert® mtb/rif testing in nepal.german nepal tb project, national tuberculosis reference laboratory, kathmandu, nepal.201628000586
ifn-γ promoter polymorphisms do not affect quantiferon® tb gold in-tube test results in a canadian population.several studies have shown polymorphisms within the interferon-gamma (ifn-γ) promoter influence cytokine expression. the interferon-gamma release assay (igra) relies on the ability to produce ifn-γ in response to tuberculosis (tb) specific antigens. this study determined the relationship between the ifn-γ +874 a/t promoter polymorphism and the performance of the quantiferon®-tb gold in-tube (qft-git) test in an ethnically diverse canadian population.201628000585
lyophilization of an adjuvanted mycobacterium tuberculosis vaccine in a single-chamber pharmaceutical cartridge.although substantial effort has been made in the development of next-generation recombinant vaccine systems, maintenance of a cold chain is still typically required and remains a critical challenge in effective vaccine distribution. the ability to engineer alternative containment systems that improve distribution and administration represents potentially significant enhancements to vaccination strategies. in this work, we evaluate the ability to successfully lyophilize a previously demonstrated ...201628000085
prothionamide susceptibility testing of mycobacterium tuberculosis using the resazurin microtitre assay and the bactecmgit 960 system.resazurin microtitre assay (rma) has been successfully used to detect minimal inhibitory concentrations (mics) of both first-line and several second-line drugs in drug susceptibility testing (dst) of mycobacterium tuberculosis (mtb). in this study, we firstly compared prothionamide (pth) susceptibility testing of mycobacterium tuberculosis (mtb) using resazurin microtitre assay (rma) and mgit. overall, the sensitivity and specificity of rma for detecting pth susceptibility was 96.5% [95% confide ...201628000029
a perspective of the diagnosis and management of congenital tuberculosis.tuberculosis continues to be a prevalent disease in the world and a global public health issue in many countries. the disease is more complicated in pregnant women because it imperils unborn offspring and results in congenital tuberculosis later if undiagnosed and untreated. congenital tuberculosis is rare entity and an uncommon disease along with a high mortality rate. congenital tuberculosis, a severe clinical type of tuberculosis caused by mycobacterium tuberculosis, is a serious and fatal di ...201627999684
immunogenicity of a dna vaccine encoding ag85a-tb10.4 antigens from mycobacterium tuberculosis.tuberculosis is a life threatening disease that is partially prevented by bcg vaccine. development of more effective vaccines is an urgent priority in tb control. ag85a and tb10.4 are the members of culture filter protein (cfp) of m. tuberculosis that have high immunogenicity.201627999240
drug-resistant tuberculosis in naples, 2008-2013.drug-resistant tuberculosis (tb) is a serious threat in industrialized countries, but information from southern italy is lacking. here, we present the results of a retrospective study of tb cases diagnosed in 2008-2013 in naples, the largest city in southern italy.201627999235
a clinic-epidemiological study of head and neck tuberculosis - a single-center experience.extrapulmonary tuberculosis (eptb) accounts for less than 6% of all tuberculosis (tb) cases in poland, although in other countries (european in particular) this proportion is much higher. the study was undertaken to evaluate the clinical and epidemiological differences in patients hospitalized in one of otolaryngology departments in poland during 36 years.201628009032
pathogenic mycobacteria achieve cellular persistence by inhibiting the niemann-pick type c disease cellular pathway.tuberculosis remains a major global health concern. the ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including mycobacterium tuberculosis, achieve long-term persistence within host cells. the mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from niemann-pick disease ...201628008422
targeting dendritic cells to accelerate t-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy.the development of a tuberculosis (tb) vaccine that induces sterilizing immunity to mycobacterium tuberculosis infection has been elusive. absence of sterilizing immunity induced by tb vaccines may be due to delayed activation of mucosal dendritic cells (dcs), and subsequent delay in antigen presentation and activation of vaccine-induced cd4(+) t-cell responses. here we show that pulmonary delivery of activated m. tuberculosis antigen-primed dcs into vaccinated mice, at the time of m. tuberculos ...201628004802
tubercular sialadenitis of parotid gland - an extremely rare case series.tuberculosis is a potentially fatal infectious disease caused by mycobacterium tuberculosis. it most commonly involves the lungs (pulmonary tuberculosis), although it can involve any organ system in the body. however even in a country like india which has high burden of this disease, the tubercular invasion of parotid gland is extremely rare. here we describe two such cases. both patients were immune competent and presented with fever and swelling in the parotid region. they were diagnosed as tu ...201627998500
abdominal tuberculosis: a retrospective analysis of 45 cases.abdominal tuberculosis is defined as infection of the peritoneum, hollow or solid abdominal organs with mycobacterium tuberculosis. the peritoneum and the ileocaecal region are the most likely sites of infection and are involved in the majority of the cases by haematogenous spread or through swallowing of infected sputum from primary pulmonary tuberculosis. pulmonary tuberculosis is apparent in less than half of the patients. patients usually present with abdominal pain, and the cause is usually ...201627998492
[application of whole genome sequencing technology in the epidemiology of tuberculosis].objective: to delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis. methods: from 2009 to 2012, nine mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (vntr) patterns were reported from two tb cases designated hospitals. both whole-genome sequencing analysis (wgs) and epidemiologic investigations were performed to describe the transmission patterns of these mycobacterium tuberculosis. results: by wgs analys ...201627998414
mycobacterium tuberculosis as a cause of mandibular osteomyelitis in a young woman: a case report.tuberculosis is considered an emerging disease worldwide; in the last 10 years, its incidence has increased to more than 9.6 million cases of active tuberculosis. in 2014, it resulted in 1.5 million patient deaths. however, oral presentation with bone involvement occurs in less than 3% of all reported cases and rarely arouses clinical suspicion on initial presentation.201627998317
mycobacterium tuberculosis infections in cynomolgus monkey transplant recipients and institution of a screening program for the prevention and control of tuberculosis.tuberculosis is a major health concern in not only humans, but also in non-human primates. in this paper, we report recent cases of mycobacterium tuberculosis in cynomolgus monkeys from cambodia used in transplantation research in a korean facility and describe a program instituted to prevent and control subsequent infections.201627998279
immunogenicity and protective efficacy of the dar-901 booster vaccine in a murine model of tuberculosis.the development of a novel tuberculosis vaccine is a leading global health priority. srl172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase iii trial in hiv-infected and bcg immunized adults in tanzania. here we describe the immunogenicity and protective efficacy of dar-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.201627997597
host immunity to mycobacterium tuberculosis and risk of tuberculosis: a longitudinal study among greenlanders.human immune responses to latent mycobacterium tuberculosis (mtb) infection (ltbi) may enable individuals to control mtb infection and halt progression to tuberculosis (tb), a hypothesis applied in several novel tb vaccines. we aimed to evaluate whether immune responses to selected ltbi antigens were associated with subsequent reduced risk of progression to tb.201627997344
transmissible mycobacterium tuberculosis strains share genetic markers and immune phenotypes.successful transmission of tuberculosis depends on the interplay of human behavior, host immune responses and mycobacterium tuberculosis virulence factors. previous studies have focused on identifying host risk factors associated with increased transmission, while the contribution of specific genetic variations in mycobacterial strains themselves are still unknown.201627997216
a first insight into the genetic diversity and drug susceptibility pattern of mycobacterium tuberculosis complex in zhejiang, china.in this study, our aim was to determine the predominant genotypes among the mycobacterium tuberculosis (mtb) strains circulating in zhejiang province. in addition, we also sought to determine the potential associations between mtb genotypes and susceptibility to first-line drugs. out of these isolates, 673 (71.6%) were classified into the beijing genotype, while the other 267 (28.4%) were from non-beijing families. the highest proportion of beijing genotype was found in huzhou (80.0%) and the lo ...201627995145
discovery and optimization of two eis inhibitor families as kanamycin adjuvants against drug-resistant m. tuberculosis.drug-resistant tuberculosis (tb) is a global threat and innovative approaches such as using adjuvants of anti-tb therapeutics are required to combat it. high-throughput screening yielded two lead scaffolds of inhibitors of mycobacterium tuberculosis (mtb) acetyltransferase eis, whose upregulation causes resistance to the anti-tb drug kanamycin (kan). chemical optimization on these scaffolds resulted in potent eis inhibitors. one compound restored the activity of kan in a kan-resistant mtb strain ...201627994767
correlation of rpob mutations with minimal inhibitory concentration of rifampin and rifabutin in mycobacterium tuberculosis in an hiv/aids endemic setting, south africa.treatment of tuberculosis (tb) and hiv co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. rifabutin (rfb) is an alternative to rifampin (rif) for tb regimens and is recommended for hiv patients concurrently receiving protease inhibitors because of reduced induction of cyp3a4. this study sought to determine the proportion of rfb susceptible isolates among rif-resistant strains in a high hiv prevalence setting in south africa. in ...201627994580
diagnosis of pulmonary tuberculosis and detection of resistance to rifampin and isoniazid through direct molecular methods in stool samples.tuberculosis (tb) is an infectious disease that is caused by mycobacterium tuberculosis (m.tb). tb has high morbidity and mortality around the world.201627993874
emerging resistant clone of mycobacterium tuberculosis in west asia. 201627998587
performance of the g4 xpert(®) mtb/rif assay for the detection of mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.the xpert(®) mtb/rif (xpert) assay is a rapid pcr-based assay for the detection of mycobacterium tuberculosis complex dna (mtbc) and mutations associated with rifampin resistance (rif). an updated version introduced in 2011, the g4 xpert, included modifications to probe b and updated analytic software.201627993132
changes in host cytokine patterns of tb patients with different bacterial loads detected using 16s rrna analysis.tuberculosis (tb) has overtaken hiv as the biggest infectious disease killer, with the majority of deaths occurring in sub-saharan africa. however it is unknown how differences in bacterial load alter host immune profiles in the sputum and blood of tb patients.201627992487
understanding nontuberculous mycobacterial lung disease: it's been a long time coming.with a surprising predictability, most studies and reviews addressing therapy for nontuberculous mycobacterial (ntm) lung disease either start or end by mentioning the paucity of data from randomized and controlled trials. that is a legitimate criticism for ntm lung disease therapy, but it also somehow seems to influence attitudes toward all aspects of ntm investigation. certainly the study of ntm diseases in general and ntm lung disease in particular is a recent development. previously, ntm wer ...201627990278
corrigendum: cell division in corynebacterineae.[this corrects the article on p. 132 in vol. 5, pmid: 24782835.].201627990143
conformational response of 30s-bound if3 to a-site binders streptomycin and kanamycin.aminoglycoside antibiotics are widely used to treat infectious diseases. among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (mdr) mycobacterium tuberculosis. both drugs bind the small ribosomal subunit (30s) and inhibit protein synthesis. genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30s subunit account for this inhibition. here, we use intramolecular fret between the c- a ...201627983590
multicenter evaluation of crystal violet decolorization assay (cvda) for rapid detection of isoniazid and rifampicin resistance in mycobacterium tuberculosis.the aim of this multicenter study was to evaluate the performance of the crystal violet decolorization assay (cvda) for detection of multidrug resistant tuberculosis (mdr-tb). this study was performed in 11 centers in two phases. a total of 156 isolates were tested for inh and rif resistance. in the phase i, 106 clinical isolates were tested in the center 1-7. in the phase 2, 156 clinical isolates were tested in the center 1-6, center 8-11. eighty six of 156 tested isolates were the same in phas ...201627982061
stereoselective synthesis, docking, and biological evaluation of difluoroindanediol-based mene inhibitors as antibiotics.a stereoselective synthesis has been developed to provide all four side-chain stereoisomers of difluoroindanediol 2, the mixture of which was previously identified as an inhibitor of the o-succinylbenzoate-coa synthetase mene in bacterial menaquinone biosynthesis, having promising in vitro activity against methicillin-resistant staphylococcus aureus and mycobacterium tuberculosis. only the (1r,3s)-diastereomer inhibited the biochemical activity of mene, consistent with computational docking stud ...201627978658
new evidence for the complexity of the population structure of mycobacterium tuberculosis increases the diagnostic and biologic challenges. 201627976945
mycobacterial cell wall biosynthesis: a multifaceted antibiotic target.mycobacterium tuberculosis (mtb), the etiological agent of tuberculosis (tb), is recognized as a global health emergency as promoted by the world health organization. over 1 million deaths per year, along with the emergence of multi- and extensively-drug resistant strains of mtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-tb chemotherapeutic agents. the essential mycobacterial cell wall, sharing some common fea ...201627976597
within host evolution selects for a dominant genotype of mycobacterium tuberculosis while t cells increase pathogen genetic diversity.molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. here, ...201627973588
microarray analysis of long noncoding rna and mrna expression profiles in human macrophages infected with mycobacterium tuberculosis.macrophages play a crucial role in the control and elimination of invading mycobacterium tuberculosis (mtb), and also serve as the major residence for mtb. however, the interaction between macrophages and mtb remains to be clearly determined. although long noncoding rnas (lncrnas) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. here, we applied microarray analysis to examine lncrna and mrna expressio ...201627966580
determination of genotypic varieties and genotyping of multiple drug-resistant tuberculosis by the rflp and spoligotyping methods.the purpose of the present study was to determine the distribution and epidemiological features of mycobacteria with molecular methods.201627966321
experimental evolution of mycobacterium tuberculosis in human macrophages results in low-frequency mutations not associated with selective advantage.isolates of the human pathogen mycobacterium tuberculosis recovered from clinical samples exhibit genetic heterogeneity. such variation may result from the stressful environment encountered by the pathogen inside the macrophage, which is the host cell tubercle bacilli parasitize. to study the evolution of the m. tuberculosis genome during growth inside macrophages, we developed a model of intracellular culture in which bacteria were serially passaged in macrophage-like thp-1 cells for about 80 b ...201627959952
diagnostic test accuracy of loop-mediated isothermal amplification assay for mycobacterium tuberculosis: systematic review and meta-analysis.diagnostic test accuracy of the loop-mediated isothermal amplification (lamp) assay for culture proven tuberculosis is unclear. we searched electronic databases for both cohort and case-control studies that provided data to calculate sensitivity and specificity. the index test was any lamp assay including both commercialized kits and in-house assays. culture-proven m. tuberculosis was considered a positive reference test. we included 26 studies on 9330 sputum samples and one study on 315 extra-p ...201627958360
a healthy young woman with acute respiratory distress syndrome: an unfamiliar face of a familiar disease.the presented case features a rare manifestation of pulmonary tuberculosis in a previously healthy young woman who had acute presentation of tuberculous pneumonia complicated by acute respiratory distress syndrome. in developing countries, mycobacterium tuberculosis is an important cause of community-acquired pneumonia (cap). tb can present as an acute process and should be included in the differential diagnosis of cap. this case is special in its manifestation from several clinical perspectives ...201627957312
choroidal tuberculoma as a presenting sign of tuberculosis.choroidal tuberculoma is a rare ocular form of tuberculosis (tb) that raises both a diagnostic and a therapeutical challenge, especially when occurring without other manifestations of the disease. this study reports the case of a 27-year-old woman who had a unilateral drop of vision (20/100) with ocular pain. her fundus examination revealed an elevated juxtapapillary choroidal mass measuring 892 µm in diameter, as calculated by optical coherence tomography (oct), and associated with a serous ret ...201627956845
hydrophobic shielding drives catalysis of hydride transfer in a family of f420h2-dependent enzymes.a family of flavin/deazaflavin-dependent oxidoreductases (fdors) from mycobacteria has been recently characterized and found to play a variety of catalytic roles, including the activation of prodrugs such as the candidate anti-tuberculosis drug pretomanid (pa-824). however, our understanding of the catalytic mechanism used by these enzymes is relatively limited. to address this, we have used a combination of quantum mechanics and molecular dynamics calculations to study the catalytic mechanism o ...201627951661
rapid detection of rifampicin- and isoniazid-resistant mycobacterium tuberculosis using real-time pcr.accurate and rapid detection of drug-resistant mycobacterium tuberculosis is fundamental for the successful treatment of tuberculosis (tb).201627942356
role of toll-like receptors in tuberculosis infection.one-third of the world's population is infected with mycobacterium tuberculosis. investigation of toll-like receptors (tlrs) has revealed new information regarding the immunopathogenesis of this disease. toll-like receptors can recognize various ligands with a lipoprotein structure in the bacilli. toll-like receptor 2 and tlr-4 have been identified in association with tuberculosis infection.201627942355
blr1 and fcgr1a transcripts in peripheral blood associate with the extent of intrathoracic tuberculosis in children and predict treatment outcome.biomarkers reflecting the extent of mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (att) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. therefore, in a cohort of 99 indian children with intrathoracic tuberculosis (tb), we performed blood transcriptome kinetic analysis during att to explore 1) the association between transcriptional biomarkers in whole blood (wb) and the e ...201627941850
clinical impact and cost-effectiveness of xpert mtb/rif testing in hospitalized patients with presumptive pulmonary tuberculosis in the united states.microscopic examination of acid-fast stained sputum smears is the current standard of care in the united states to determine airborne infection isolation (aii) of inpatients with presumptive pulmonary tuberculosis (ptb). however, nucleic acid amplification testing (naat) with the xpert® mtb/rif assay (xpert) may be more efficient and less costly.201627940948
discovery of mycobacterium tuberculosis inha inhibitors by binding sites comparison and ligands prediction.drug discovery is usually focused on a single protein target; in this process, existing compounds that bind to related proteins are often ignored. we describe probis plugin, extension of our earlier probis-ligands approach, which for a given protein structure allows prediction of its binding sites and, for each binding site, the ligands from similar binding sites in the protein data bank. we developed a new database of precalculated binding site comparisons of about 290000 proteins to allow fast ...201627936766
trehalose-6-phosphate-mediated toxicity determines essentiality of otsb2 in mycobacterium tuberculosis in vitro and in mice.trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including mycobacterium tuberculosis. the most common biosynthetic route involves trehalose-6-phosphate (t6p) synthase otsa and t6p phosphatase otsb that generate trehalose from adp/udp-glucose and glucose-6-phosphate. in order to assess the drug target potential of t6p phosphatase, we generated a conditional mutant of m. tuberculosis allowing the reg ...201627936238
microglia activation in a pediatric rabbit model of tuberculous meningitis.central nervous system (cns) tuberculosis (tb) is the most severe form of extra-pulmonary tb and disproportionately affects young children where the developing brain has a unique host response. new zealand white rabbits were infected with mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologi ...201627935825
alteration in the gut microbiota provokes susceptibility to tuberculosis.the microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. in particular, they regulate immune homeostasis. recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. tuberculosis (tb) is the most devastating disease, inflicting mortality and morbidity. it remains unexplored, whether changes in the gut microbiota can provoke or prevent tb. in the current study, we have demons ...201627965663
importance of specimen pretreatment for the low-level detection of mycobacterial lipoarabinomannan in human serum.patient care and prevention of disease outbreaks rely heavily on the performance of diagnostic tests. these tests are typically carried out in serum, urine, and other complex sample matrices, but are often plagued by a number of matrix effects such as nonspecific adsorption and complexation with circulating proteins. this paper demonstrates the importance of sample pretreatment to overcome matrix effects, enabling the low-level detection of a disease marker for tuberculosis (tb). the impact of p ...201627934985
sulfonamide-based inhibitors of aminoglycoside acetyltransferase eis abolish resistance to kanamycin in mycobacterium tuberculosis.a two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. by high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of mycobacterium tuberculosis acetyltransferase eis, whose upregulation causes resistance to the aminoglycoside (ag) antibiotic kanamycin a (kan) in mycobacteri ...201627933949
biosynthesis and regulation of sulfomenaquinone, a metabolite associated with virulence in mycobacterium tuberculosis.sulfomenaquinone (smk) is a recently identified metabolite that is unique to the mycobacterium tuberculosis (m. tuberculosis) complex and is shown to modulate its virulence. here, we report the identification of the smk biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome p450 gene (cyp128) and a gene of unknown function, rv2269c. we demonstrate that cyp128 and stf3 are sufficient for the biosynthesis of smk from menaquinone and r ...201627933784
systemic expression of notch ligand delta-like 4 during mycobacterial infection alters the t cell immune response.the notch ligand delta-like 4 (dll4) is known to fine-tune the cd4(+) t cell cytokine response. dll4 is expressed on the surface of antigen-presenting cells (apcs) in a myd88-dependent manner. we found that dll4 expression was upregulated on bone marrow progenitor cells and apcs in mice infected with bcg mycobacterium. transfer of dll4(+) progenitor cells from infected hosts resulted in an increase dll4(+) myeloid cells in the spleen, indicating that expression of the dll4 gene is propagated thr ...201627933064
risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/aids-coinfected patients under tuberculosis treatment.tuberculosis (tb) is a worldwide public health problem. it is a contagious and grave disease caused by mycobacterium tuberculosis. current drugs such as isoniazid, pyrazinamide, and rifampicin used for the treatment of tuberculosis are potentially hepatotoxic and can lead to drug hepatitis. in order to improve the follow-up of tb patients in cameroon, we carried out a study which aimed to evaluate the hepatotoxicity risk factors associated with anti-tb drugs.201627931691
evaluation of the genotype mtbdrplus assay for detection of rifampicin- and isoniazid-resistant mycobacterium tuberculosis isolates in central ethiopia.multidrug-resistant tuberculosis (mdr-tb) is growing globally and becoming a major challenge for national tb control programs. therefore, rapid identification of mdr strains of mycobacterium tuberculosis and monitoring their transmission could contribute significantly to the control of tb. the genotype mtbdrplus assay has been recommended by the world health organization to identify rifampicin (rif)- and isoniazid (inh)-resistant m. tuberculosis isolates. this study was carried out to evaluate t ...201627931690
rapid drug-susceptibility testing of mycobacterium tuberculosis clinical isolates to first-line antitubercular drugs by nitrate reductase assay: a comparison with proportion method.early initiation of therapy in patients with tuberculosis is imperative for its control. conventional methods of susceptibility testing such as the proportion method (pm) require visual detection and counting of colonies that takes up to 6weeks. rapid and simple phenotypic methods that have been endorsed by the world health organization can serve as alternatives.201627931689
l-form transformation phenomenon in mycobacterium tuberculosis associated with drug tolerance to ethambutol.cell wall-deficient bacterial forms (l-forms) may occur along with resistance to factors that trigger their appearance. it is of interest to study the relationship between the l-form transformation of mycobacterium tuberculosis and the exhibition of drug tolerance to ethambutol (emb), an inhibitor of cell wall synthesis.201627931687
inhibition of apoptosis by rv2456c through nuclear factor-κb extends the survival of mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. apoptosis has been shown to be mycobactericidal, to activate cd8(+) t cells, and to be modulated by mycobacterial proteins. since few mycobacterial proteins have so far been directly implicated in the interactions between m. tuberculosis and host cell apoptosis, we screened m. tuberculosis h37rv transposon mutants to identify m ...201627931684
mycobacterial contamination of bronchoscopes: challenges and possible solutions in low resource settings.the use of bronchoscopes has increased in tuberculosis (tb) diagnostics to circumvent the diagnostic challenges that are associated with low sputum volume and smear-negative tb. in healthcare facilities situated in low income countries that have a high burden of tb, adequate decontamination of bronchoscopes is a challenge and often overlooked to save on time and costs. this amplifies the risk of outbreaks and pseudo-outbreaks due to mycobacterium tuberculosis and nontuberculosis mycobacteria. in ...201627931681
diagnosing tuberculosis in the 21st century - dawn of a genomics revolution?tuberculosis (tb) ranks alongside hiv as the leading cause of death worldwide, killing 1.5million people in 2014. traditional laboratory techniques do not provide sufficiently rapid results to inform clinicians on appropriate treatment, especially in the face of increasingly prevalent drug-resistant tb. rapid molecular methods such as pcr and lamp are vital tools in the fight against tb, however, rapid advances in next generation sequencing (ngs) technology are allowing increasingly rapid and ac ...201627931678
assuming the role of mitochondria in mycobacterial infection.tuberculosis is one of the leading causes of death by mycobacterium tuberculosis (mtb) affecting millions of people worldwide. mycobacterium species enter host macrophages during infection and target various cellular organelles and their function for their own benefit. mitochondria appear to be among the important targets for bacterial pathogens. mtb and other pathogenic bacteria secrete various proteins that initiate structural changes in mitochondria to modulate its function. additionally, vir ...201627931677
pyrazinamide susceptibility testing: proposed new standard with the bactectm mgittm 960 system.the susceptibility of 253 mycobacterium tuberculosis complex isolates to pyrazinamide (pza) was assessed using the bactectm mgittm 960 (m960) system. resistant strains underwent paired repeat testing using 1) a critical concentration of 200 g/ml (pza-200), and 2) a reduced inoculum of 0.25 ml. they were also examined using the bactec 460 (b460) reference method and investigated for pnca mutations. on m960, 37 isolates were resistant. in the pza-200 assay, 20 of these were resistant and 17 suscep ...201627931346
evaluation of omnigenesputum-stabilised sputum for long-term transport and xpert mtb/rif testing in nepal.german nepal tb project, national tuberculosis reference laboratory, kathmandu, nepal.201627931343
ifn- promoter polymorphisms do not affect quantiferon tb gold in-tube test results in a canadian population.several studies have shown polymorphisms within the interferon-gamma (ifn-) promoter influence cytokine expression. the interferon-gamma release assay (igra) relies on the ability to produce ifn- in response to tuberculosis (tb) specific antigens. this study determined the relationship between the ifn- +874 a/t promoter polymorphism and the performance of the quantiferon-tb gold in-tube (qft-git) test in an ethnically diverse canadian population.201627931341
impact of contact investigation and tuberculosis screening among high-risk groups in denmark.the objective of tuberculosis (tb) screening in low-incidence countries is to identify tb patients earlier, ideally to improve health outcomes and reduce mycobacterium tuberculosis transmission. in this retrospective study, we compare hospitalisation (morbidity) and smear positivity rates (infectiousness) in tb patients identified through active case finding (acf) with patients identified through passive case finding (pcf).201627931331
rapid detection of mycobacterium tuberculosis strains resistant to isoniazid and/or rifampicin: standardization of multiplex polymerase chain reaction analysis.drug susceptibility testing using molecular techniques can enhance the identification of drug-resistant mycobacterium tuberculosis two multiplex real-time polymerase chain reaction (qpcr) assays were developed to detect the most common resistance-associated mutations to isoniazid (katgs315t, inha-15c → t), and rifampicin (rpobh526y and rpobs531l). to assess the species specificity of the qpcr, we selected 31 nontuberculous mycobacteria (ntm) reference strains belonging to 17 species from the pub ...201627928076
cerebral tuberculomas in a patient with hairy cell leukaemia treated with cladribine.a 67-year-old man was treated with cladribine for hairy cell leukaemia. a few weeks later, he presented with persistent headaches, intermittent hypoesthesia of the right upper limb and language impairment. brain ct scan showed 3 contrast-enhancing lesions. mri revealed infracentimetric nodular lesions with restricted diffusion. one of the lesions was surgically removed and tested positive for acid-fast bacilli. moreover, mycobacterium tuberculosis was confirmed by pcr. antituberculous drugs were ...201627927706
frequency and distribution patterns of opportunistic infections associated with hiv/aids in uganda.we conducted a study to assess the frequency and distribution patterns of selected opportunistic infections (ois) and opportunistic cancers (ocs) in different geographical areas before and after haart in uganda.201627927247
does calcium channel blockade have a role in prevention of expression of sepsis in renal transplant recipients?many antihypertensive agents have been demonstrated to assist in preservation of kidney function, among them those that modulate calcium channels. calcium channel blockers may also be of value in protecting hemodialysis patients from complications of sepsis. in diabetic recipients of kidney transplant allografts treated with cyclosporine, calcium channel blockade has been retrospectively linked to improved graft preservation and to fewer episodes of sepsis. this brief review outlines clinical an ...201627920569
mycobacterium tuberculosis esxh inhibits escrt-dependent cd4(+) t-cell activation.mycobacterium tuberculosis (mtb) establishes a persistent infection, despite inducing antigen-specific t-cell responses. although t cells arrive at the site of infection, they do not provide sterilizing immunity. the molecular basis of how mtb impairs t-cell function is not clear. mtb has been reported to block major histocompatibility complex class ii (mhc-ii) antigen presentation; however, no bacterial effector or host-cell target mediating this effect has been identified. we recently found th ...201627918526
recombinant lipoprotein rv1016c derived from mycobacterium tuberculosis is a tlr-2 ligand that induces macrophages apoptosis and inhibits mhc ii antigen processing.tlr2-dependent cellular signaling in mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class ii major histocompatibility complex (mhc-ii) molecules antigen processing, leading to evasion of surveillance. mycobacterium tuberculosis (mtb) lipoproteins are an important class of toll-like receptor (tlr) ligand, and identified as specific components that mediate these effects. in this study, we identified and characterized mtb lipoprotein rv1016c (lpqt) as a cell wall asso ...201627917375
detection of the tuberculosis antigenic marker mannose-capped lipoarabinomannan in pretreated serum by surface-enhanced raman scattering.the ability to detect tuberculosis (tb) continues to be a global health care priority. this paper describes the development and preliminary assessment of the clinical accuracy of a heterogeneous immunoassay that integrates a serum pretreatment process with readout by surface-enhanced raman scattering (sers) for the low-level detection of mannose-capped lipoarabinomannan (manlam). manlam is a major virulence factor in the infectious pathology of mycobacterium tuberculosis (mtb) that has been foun ...201627924983
il-21-dependent expansion of memory-like nk cells enhances protective immune responses against mycobacterium tuberculosis.natural killer (nk) cells are traditionally considered as innate cells, but recent studies suggest that nk cells can distinguish antigens, and that memory nk cells expand and protect against viral pathogens. limited information is available about the mechanisms involved in memory-like nk cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. in the current study, using a mouse model of tuberculosis (tb) infection, we found that interferon-gamma pr ...201627924822
cd36-mediated uptake of surfactant lipids by human macrophages promotes intracellular growth of mycobacterium tuberculosis.mycobacterium tuberculosis imposes a large global health burden as the airborne agent of tuberculosis. mycobacterium tuberculosis has been flourishing in human populations for millennia and is therefore highly adapted to the lung environment. alveolar macrophages, a major host cell niche for m. tuberculosis, are not only phagocytose inhaled microbes and particulate matter but are also crucial in catabolizing lung surfactant, a lipid-protein complex that lines the alveolar spaces. because macroph ...201627913648
targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates.the ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against mycobacterium tuberculosis and other infectious agents. antifolates are an underutilized drug class in tuberculosis (tb) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. based on the observation that exogenously supplied p-aminobenzoic acid (paba) can antagonize the action of antifolates that interact with dihydropteroate synth ...201627905500
effect of common and experimental anti-tuberculosis treatments on mycobacterium tuberculosis growing as biofilms.much is known regarding the antibiotic susceptibility of planktonic cultures of mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (tb). as planktonically-grown m. tuberculosis are unlikely to be entirely representative of the bacterium during infection, we set out to determine how effective a range of anti-mycobacterial treatments were against m. tuberculosis growing as a biofilm, a bacterial phenotype known to be more resistant to antibiotic treatment. ligh ...201627904808
a comparison of the sensititre mycotb plate, the bactec mgit 960, and a microarray-based molecular assay for the detection of drug resistance in clinical mycobacterium tuberculosis isolates in moscow, russia.the goal of this study was to compare the consistency of three assays for the determination of the drug resistance of mycobacterium tuberculosis (mtb) strains with various resistance profiles isolated from the moscow region.201627902737
heterozygote advantage of the rs3794624 polymorphism in cyba for resistance to tuberculosis in two chinese populations.phagocyte nicotinamide adenine dinucleotide phosphate (nadph) oxidase complex is a key enzyme that catalyzes the production of reactive oxygen species, which mediate oxygen-dependent killing of microorganisms, such as mycobacterium tuberculosis. p22phox, encoded by cyba, is the key regulatory subunit of nadph oxidase. our study aimed to investigate the association of cyba polymorphisms with susceptibility to tuberculosis. three snps (rs9932581, rs3794624 and rs4673) were genotyped in the discove ...201627901128
rifampicin-induced adrenal crisis in a patient with tuberculosis: a therapeutic challenge.a 55-year-old indian man presented with productive cough and a large left pleural effusion. pleural fluid culture grew mycobacterium tuberculosis, and he was started on antituberculosis therapy. one week later, the patient presented to hospital with drowsiness, dehydration and hypotension. he was transferred to critical care and only improved after starting hydrocortisone and stopping rifampicin. his short synacthen test subsequently confirmed primary adrenal insufficiency, and a ct of the abdom ...201627899384
title: role of matrix metalloproteinase -9 in progression of tuberculous meningitis: a pilot study in patients at different stages of the disease.tbm (tuberculous meningitis) is severe form of tuberculosis causing death of one third of the affected individuals or leaving two-third of the survivors disabled. mmp-9 (matrix metalloproteinase-9) is produced by the central nervous system in a variety of inflammatory conditions and has a role in the breakdown of extracellular matrix and blood-brain barrier.201627899068
radioprotective effects of heat-killed mycobacterium tuberculosis in cultured cells and radiosensitive tissues.exposure to ionizing radiation (ir) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. novel safe and effective radioprotectant is urgently required. it has been reported toll like receptor 2 (tlr2) plays a critical role in radioresistance. in this study, we demonstrated the protective effects of heat-killed mycobacterium tuberculosis (hkmt), a potent tlr2 agonist, against ir.201627898411
human host range of mycobacterium tuberculosis.a new study demonstrates that the most widespread lineage of the causative agent of tuberculosis consists of both globally distributed and geographically restricted sublineages. the geographically restricted sublineages are likely able to infect only specific human populations, whereas the globally distributed ones likely have a broader human host range.201627898082
changes in the membrane-associated proteins of exosomes released from human macrophages after mycobacterium tuberculosis infection.tuberculosis (tb) is the deadliest infectious disease worldwide. one obstacle hindering the elimination of tb is our lack of understanding of host-pathogen interactions. exosomes, naturally loaded with microbial molecules, are circulating markers of tb. changes in the host protein composition of exosomes from mycobacterium tuberculosis (mtb)-infected cells have not been described, can contribute to our understanding of the disease process, and serve as a direct source of biomarkers or as capture ...201627897233
cytosolic proteome profiling of aminoglycosides resistant mycobacterium tuberculosis clinical isolates using maldi-tof/ms.emergence of extensively drug resistant tuberculosis (xdr-tb) is the consequence of the failure of second line tb treatment. aminoglycosides are the important second line anti-tb drugs used to treat the multi drug resistant tuberculosis (mdr-tb). main known mechanism of action of aminoglycosides is to inhibit the protein synthesis by inhibiting the normal functioning of ribosome. primary target of aminoglycosides are the ribosomal rna and its associated proteins. various mechanisms have been pro ...201627895634
nontuberculous mycobacteria lymphadenitis: a case report.atypical mycobacteria, also known as nontuberculous mycobacteria (ntm) includes acid-fast bacteria other than mycobacterium tuberculosis. ntm can be isolated from a variety of environmental sources including water, food products, domestic animals, and soil; human exposure is typically from soil to the oral cavity and respiratory tract. diagnosis of ntm is suspected in children less than five years old with subacute, unilateral, non-tender cervicofacial lymphadenitis in combination with a history ...201627909634
tuberculosis drug resistance in bamako, mali, from 2006 to 2014.although drug resistance tuberculosis is not a new phenomenon, mali remains one of the "blank" countries without systematic data.201627894266
virulence of mycobacterium tuberculosis after acquisition of isoniazid resistance: individual nature of katg mutants and the possible role of ahpc.in the last decade, there were 10 million new tuberculosis cases per year globally. around 9.5% of these cases were caused by isoniazid resistant (inhr) mycobacterium tuberculosis (mtb) strains. although isoniazid resistance in mtb is multigenic, mutations in the catalase-peroxidase (katg) gene predominate among the inhr strains. the effect of these drug-resistance-conferring mutations on mtb fitness and virulence is variable. here, we assessed differences in bacterial growth, immune response an ...201627893795
new genome-wide algorithm identifies novel in-vivo expressed mycobacterium tuberculosis antigens inducing human t-cell responses with classical and unconventional cytokine profiles.new strategies are needed to develop better tools to control tb, including identification of novel antigens for vaccination. such mtb antigens must be expressed during mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. using genome-wide transcriptomics of mtb infected lungs we developed data sets and methods to identify ive-tb (in-vivo expressed mtb) antigens expressed in the lung. quantitative expression analysis of 2,068 mtb genes from t ...201627892960
mycobacterium tuberculosis beijing genotype in western iran: distribution and drug resistance.mycobacterium tuberculosis beijing genotype is gaining importance all over the world because this genotype is highly prevalent in several areas and is also frequently associated with drug resistance.201627891336
analysis of the immune response of human dendritic cells to mycobacterium tuberculosis by quantitative proteomics.the cellular immune response for mycobacterium tuberculosis (m. tuberculosis) infection remained incompletely understood. to uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (lc-ms/ms) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed m. tub ...201626957948
phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents.multi- and extensively drug-resistant tuberculosis (tb) is a global threat to human health. it requires immediate action to seek new antitubercular compounds and devise alternate strategies. nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. in view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria.201627217751
preparation of monoclonal antibodies against mannosylated lipoarabinomannan (manlam), a surface antigen of bcg vaccine produced in iran.bacille calmette-guerin (bcg) vaccine is the only vaccine that is used against mycobacterium tuberculosis, but its efficacy is limited in mycobacterium-endemic regions. one of the major antigens present on the cell envelope of the vaccine that suppresses the immune system is mannosylated lipoarabinomannan (manlam).201626962517
towards new tb vaccines: what are the challenges?new and effective tuberculosis (tb) vaccines are urgently needed to control pulmonary tb, and in particular to prevent the spread of drug-resistant strains of mycobacterium tuberculosis. these drug-resistant strains can range from those resistant to first-line drugs to those that are almost impossible to treat. to develop new and effective vaccines for hiv and malaria has been difficult and it is proving to be just as challenging for tb. tb is a complicated disease with a spectrum from apparentl ...201626960944
expressions of antimicrobial peptides ll-37, human beta defensin-2 and -3 in the lesions of cutaneous tuberculosis and tuberculids.antimicrobial peptides, including cathelicidin ll-37, human beta defensin (hbd)-2, and hbd-3, are important elements of the innate immune response and involved in modulation of the adaptive immunity, and they also play an important role in cutaneous defense against mycobacterium tuberculosis.201626960373
epidemiology and clinical characteristics of pediatric drug-resistant tuberculosis in chongqing, china.to gain insight into the epidemiology of childhood drug resistant tuberculosis (dr-tb) in china that has the second largest burden of tb and the largest number of multidrug resistant (mdr) tb cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-tb drugs (isoniazid, rifampicin, streptomycin and ethambutol) using mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric tb cases diagnosed in the children's hospital of chon ...201626959480
a mycobacterial perspective on tuberculosis in west africa: significant geographical variation of m. africanum and other m. tuberculosis complex lineages.phylogenetically distinct mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity. consequently, understanding mycobacterial population structures phylogeographically is essential for design, interpretation and generalizability of clinical trials. comprehensive efforts are lacking to date to establish the west african mycobacterial population structure on a sub-continental scale, which has diagnostic implications and can inform the design of clinical tb trials.201626964059
neuroimaging in tuberculous meningitis.tuberculous meningitis is a serious infection caused by mycobacterium tuberculosis. early diagnosis is the key to success of treatment. neuroimaging plays a crucial role in the early and accurate diagnosis of tuberculous meningitis and its disabling complications. magnetic resonance imaging is considered superior to computed tomography. neuroimaging characteristics include leptomeningeal and basal cisternal enhancement, hydrocephalus, periventricular infarcts, and tuberculoma. partially treated ...201626954796
role of the cys154arg substitution in ribosomal protein l3 in oxazolidinone resistance in mycobacterium tuberculosis.we expressed the wild-type rplc and mutated rplc (cys154arg) genes, respectively, in mycobacterium tuberculosis h37ra and h37rv in an attempt to delineate the role of rplc (cys154arg) regarding oxazolidinone resistance. an increase of the mics of linezolid (lzd) and sutezolid (pnu-100480, pnu) against the recombinant mycobacteria with overexpressed rplc mutation (cys154arg) was found, suggesting the rplc gene is a determinant of bacillary susceptibilities to lzd and pnu.201626953211
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