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cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the brazilian unified health care system.we estimated the costs of a molecular test for mycobacterium tuberculosis and resistance to rifampin (xpert mtb/rif) and of smear microscopy, within the brazilian sistema único de saúde (sus, unified health care system). in sus laboratories in the cities of rio de janeiro and manaus, we performed activity-based costing and micro-costing. the mean unit costs for xpert mtb/rif and smear microscopy were r$35.57 and r$14.16, respectively. the major cost drivers for xpert mtb/rif and smear microscopy ...201626785963
pilot study of a rapid and minimally instrumented sputum sample preparation method for molecular diagnosis of tuberculosis.nucleic acid amplification testing (naat) enables rapid and sensitive diagnosis of tuberculosis (tb), which facilitates treatment and mitigates transmission. nucleic acid extraction from sputum constitutes the greatest technical challenge in tb naat for near-patient settings. this report presents preliminary data for a semi-automated sample processing method, wherein sputum is disinfected and liquefied, followed by purelyse(®) mechanical lysis and solid-phase nucleic acid extraction in a miniatu ...201626785769
mycobacterium tuberculosis-specific il-21+ifn-γ+cd4+ t cells are regulated by il-12.in the current study of mycobacterium tuberculosis (mtb)-specific t and b cells, we found that mtb-specific peptides from early secreted antigenic target-6 (esat-6) and culture filtrate protein-10 (cfp-10) induced the expression of il-21 predominantly in cd4(+) t cells. a fraction of il-21-expressing cd4(+) t cells simultaneously expressed th1 cytokines but did not secrete th2 or th17 cytokines, suggesting that mtb-specific il-21-expressing cd4(+) t cells were different from th1, th2 and th17 su ...201626785168
molecular principles behind pyrazinamide resistance due to mutations in pand gene in mycobacterium tuberculosis.the latest resurrection of drug resistance poses serious threat to the treatment and control of the disease. mutations have been detected in pand gene in the mycobacterium tuberculosis (mtb) strains. mutation of histidine to arginine at residue 21 (h21r) and isoleucine to valine at residue 29 (i49v) in the non-active site of pand gene has led to pza resistance. this study will help in reconnoitering the mechanism of pyrazinamide (pza) resistance caused due to double mutation identified in the pa ...201626784657
variable transcriptional adaptation between the laboratory (h37rv) and clinical strains (s7 and s10) of mycobacterium tuberculosis under hypoxia.tuberculosis continues to be a major public health problem in many parts of the world, despite intensified efforts taken to control the disease. the remarkable success of m. tuberculosis as a pathogen is largely due to its ability to persist within the host for long periods. to develop the effective intervention strategies, understanding the biology of persistence is highly required. accumulating evidences showed oxygen deprivation (hypoxia) as a potential stimulus for triggering the transition ...201626780642
characterization of mutations in streptomycin-resistant mycobacterium tuberculosis isolates in sichuan, china and the association between beijing-lineage and dual-mutation in gidb.mutations in rpsl, rrs, and gidb are well linked to streptomycin (str) resistance, some of which are suggested to be potentially associated with mycobacterium tuberculosis genotypic lineages in certain geographic regions. in this study, we aimed to investigate the mutation characteristics of streptomycin resistance and the relationship between the polymorphism of drug-resistant genes and the lineage of m. tuberculosis isolates in sichuan, china. a total of 227 m. tuberculosis clinical isolates, ...201626786661
novel mutations conferring resistance to kanamycin in mycobacterium tuberculosis clinical isolates from northern india.twenty-nine kanamycin resistant clinical isolates of mycobacterium tuberculosis from northern india were screened to evaluate genetic mutations in rrs gene, eis gene with its promoter, and whib7 gene along with its 5'utr. 14 strains (~48.0%) collectively exhibited mutations in rrs, eis or whib7 target regions. while the highest frequency of mutations was found in rrs gene, eis and whib7 loci displayed novel mutations. the novel mutations displayed by eis and whib7 loci were found to be associate ...201626786660
a novel role of yin-yang-1 in pulmonary tuberculosis through the regulation of the chemokine ccl4.mycobacterium tuberculosis (m. tb) is the etiological agent of pulmonary tuberculosis (tb); this disease remains a worldwide health problem. yin-yang-1 (yy1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. however, the role of yy1 in tb remains unknown. the aim of this study was to elucidate the role of yy1 in the regulation of ccl4 and its implication in tb. we determined whether yy1 regulates ccl4 using reporter plasmids, chip and ...201626786659
mtbvac vaccine is safe, immunogenic and confers protective efficacy against mycobacterium tuberculosis in newborn mice.development of novel more efficient preventive vaccines against tuberculosis (tb) is crucial to achieve tb eradication by 2050, one of the millennium development goals (mdg) for the current century. mtbvac is the first and only live attenuated vaccine based on a human isolate of mycobacterium tuberculosis developed as bcg-replacement strategy in newborns that has entered first-in-human adult clinical trials. in this work, we characterize the safety, immunogenicity and protective efficacy of mtbv ...201626786657
detection of igg1 antibodies against mycobacterium tuberculosis dosr and rpf antigens in tuberculosis patients before and after chemotherapy.diagnosis of tuberculosis (tb) remains challenging. serum igg1 antibodies against mycobacterium tuberculosis active growth phase antigens (esat-6/cfp-10, rv0717 and rv3353), dosr regulon-encoded proteins (rv1733, rv1737, rv2628 and rv2029), and resuscitation-promoting factors (rv0867 and rv2389) were evaluated in tb patients using elisa. active tb patients showed elevated levels of igg1 antibodies against esat-6/cfp-10, rv0717, rv3353, rv1733, rv2628, rv2029 and rv0867 in comparison to healthy c ...201626786656
irgm gene polymorphisms and haplotypes associate with susceptibility of pulmonary tuberculosis in chinese hubei han population.human immunity-related gtpase m (irgm) is found to play an important role in defense against intracellular pathogen mycobacterium tuberculosis (m. tuberculosis) in vitro by regulating autophagy. the objective of the study was to determine the association between irgm polymorphisms and susceptibility to pulmonary tuberculosis (ptb) in chinese hubei han population. in this study, 237 ptb patients and 269 healthy controls were screened for irgm promoter single nucleotide polymorphisms (snps) by gen ...201626786655
first insight into the genetic population structure of mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in egypt.the present study aimed to assess the population structure of mycobacterium tuberculosis (mtb) isolates from egypt. a total of 230 mtb isolates were analysed using spoligotyping, large sequence polymorphism (lsps), mycobacterial interspersed repetitive unit-variable number tandem repeat (miru-vntr) typing and multi-locus sequence typing (mlst). the majority of isolates (93.0%) belonged to lineage 4, including 44.3, 13.4 and 10.8% of the ill-defined t clade, lam and haarlem families, respectively ...201626786649
ultra low dose aerosol challenge with mycobacterium tuberculosis leads to divergent outcomes in rhesus and cynomolgus macaques.well characterised animal models that can accurately predict efficacy are critical to the development of an improved tb vaccine. the use of high dose challenge for measurement of efficacy in non-human primate models brings the risk that vaccines with the potential to be efficacious against natural challenge could appear ineffective and thus disregarded. therefore, there is a need to develop a challenge regimen that is more relevant to natural human infection. this study has established that ultr ...201626786648
hypoxia promotes mycobacterium tuberculosis-specific up-regulation of granulysin in human t cells.oxygen tension affects local immune responses in inflammation and infection. in tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular mycobacterium tuberculosis (m.tb). the effect of oxygen restriction on t cell-mediated antimicrobial effector mechanisms is unknown. therefore we determined the influence of hypox ...201626613797
nod-2 and tlr-4 signaling reinforces the efficacy of dendritic cells and reduces the dose of tb drugs against mycobacterium tuberculosis.tuberculosis (tb) is one of the leading killer infectious diseases. tb patients are inflicted with devastating side effects and the toxicity of a lengthy drug regime, accentuating an urgent need to explore newer and safer treatment methods. recently, an improved understanding of host-pathogen interaction has opened new avenues for tb treatment, including immunotherapy. this has emboldened us to devise a novel strategy to restrict mycobacterium tuberculosis(mtb) growth by activating dendritic cel ...201626613532
a note on derivatives of isoniazid, rifampicin, and pyrazinamide showing activity against resistant mycobacterium tuberculosis.drug-resistant tuberculosis (dr-tb) is a serious problem that impedes the success of the tb control program. of note, multidrug-resistant (mdr)-tb and extensively drug-resistant (xdr)-tb have certainly complicated the scenario. one of the possible strategies to overcome drug resistance in an economic and simple manner would involve modification of existing anti-tb drugs to obtain derivatives that can work on resistant tb bacilli. these may have improved half-life and increased bioavailability, b ...201626613382
tuberculous liver abscess in an immunocompetent child with pulmonary tuberculosis as a cause of fever of unknown origin.infectious diseases are the leading cause of fuo. a case of prolonged fever with hepatic and pulmonary tuberculosis as a final diagnosis is herein presented. a 4-year-old, otherwise healthy boy presented with an axillary temperature of up to 39.5ºc for the previous 3 weeks. his medical history revealed an occasional increase in body temperature up to 38.5ºc for the last 6 months. physical examination revealed coarse breath sounds on the basal lung area. chest x-ray showed mediastinal lymphadenom ...201626613227
a comparative modeling and molecular docking study on mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis.an alarming rise of multidrug-resistant mycobacterium tuberculosis strains and the continuous high global morbidity of tuberculosis have reinvigorated the need to identify novel targets to combat the disease. the enzymes that catalyze the biosynthesis of peptidoglycan in m. tuberculosis are essential and noteworthy therapeutic targets. in this study, the biochemical function and homology modeling of muri, murg, mray, dape, dapa, alr, and ddl enzymes of the cdc1551 m. tuberculosis strain involved ...201626612108
not all the infected develop the disease - a "lotus and cactus" model.the immunogenetic dictum "not all the infected develop the disease" can best be explained by a "lotus and cactus" model. lotuses grow in ponds and cacti in deserts: analogously, we can say that tubercle patient's lung (genetic makeup) functions as an ideal 'broth' for mycobacterium tuberculosis (m.tb) germs to grow, but not the lungs of an endemic control. hla association studies from europe to asia since 1983 till date, have shown a persistent hla dr2 (15) association. further, hla dr2 and non- ...201626611827
b cells as multi-functional players during mycobacterium tuberculosis infection and disease.immunity to tuberculosis is still understood to be driven and maintained by t-cell derived immune responses. with a steady influx of data, it is becoming clear that b cells, the mediators of humoral immunity, have the capacity to function in roles not previously appreciated within the traditional b cell dogma. in this review we aim to discuss b cells, from its generation through to its functioning as effectors in both the innate and adaptive immune response, within the tuberculosis domain.201626611659
high-resolution ct findings of pulmonary mycobacterium tuberculosis infection in renal transplant recipients.renal transplantation recipients are at increased risk of mycobacterium tuberculosis infection because of immunosuppression. the aim of this study was to assess high-resolution ct (hrct) findings in renal transplantation recipients diagnosed with pulmonary tuberculosis (tb).201626607644
double staining of bacilli and antigen ag85b improves the accuracy of the pathological diagnosis of pulmonary tuberculosis.a pathological examination plays an important role in the confirmation of a diagnosis of tuberculosis, especially for smear- and culture-negative cases. however, conventional ziehl-neelsen staining and histological tests lack sensitivity and specificity.201626614787
transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (pbmc) that discriminate individuals with latent tuberculosis infection (ltbi) from those with pulmonary tuberculosis (ptb) in subjects with non-insulin-dependent diabetes mellitus (niddm) and in individuals without niddm. using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with mycobacterium tuberculosis (mtb) or a mutant (δsigh) representing a no ...201626628192
functional polymorphisms of monocyte chemoattractant protein-1 gene and pott's disease risk.monocyte chemoattractant protein-1 (mcp-1/ccl2), a key player in immune-mediated responses against mycobacterium tuberculosis, is encoded by a polymorphic gene. functionally relevant polymorphic variations in the mcp-1 gene have been associated with both susceptibility to and protection against tuberculosis-related disorders. here, we investigated the potential impact of some of these polymorphisms on pott's disease risk in a patient cohort from algeria.201626626202
resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from pakistan.201626626164
the marr family transcription factor rv1404 coordinates adaptation of mycobacterium tuberculosis to acid stress via controlled expression of rv1405c, a virulence-associated methyltransferase.coordinated regulation of gene expression is essential for pathogen adaptation in vivo. understanding the control of these virulence circuits in the tb pathogen mycobacterium tuberculosis is a key challenge if we are to increase our basic understanding of how this organism establishes infection. in this study we focused on the transcriptional regulator rv1404 that shows similarity to the marr family of transcriptional repressors. rv1404 derepresses a set of genes in vivo that have been implicate ...201626615221
an in silico approach for identification of potential anti-mycobacterial targets of vasicine and related chemical compounds.tuberculosis (tb) is known to mankind as one of the most pervasive and persistent of diseases since the early days of civilization. the growing resistance of the causative pathogen mycobacterium tuberculosis to the standard drug regimen for tb poses further difficulty in its treatment and control. screening of novel plant-derived compounds with promising anti-tubercular activity has been cited as a prospective route for new anti-tubercular drug discovery and design. justicia adhatoda l. is a per ...201626632438
comparative evaluation of several gene targets for designing a multiplex-pcr for an early diagnosis of extrapulmonary tuberculosis.diagnosis of extrapulmonary tuberculosis (eptb) poses serious challenges. a careful selection of appropriate gene targets is essential for designing a multiplex-polymerase chain reaction (m-pcr) assay.201626632387
synthesis of characteristic mycobacterium peptidoglycan (pgn) fragments utilizing with chemoenzymatic preparation of meso-diaminopimelic acid (dap), and their modulation of innate immune responses.peptidoglycan (pgn) is a major component of bacterial cell wall and is recognized as a potent immunostimulant. the pgn in the cell envelope of mycobacterium tuberculosis has been shown to possess several unique characteristics including the presence of n-glycolyl groups (in addition to n-acetyl groups) in the muramic acid residues, and amidation of the free carboxylic acid of d-glu or of meso-dap in the peptide chains. using a newly developed, highly stereoselective, chemoenzymatic approach for ...201626631868
the effect of hiv coinfection, haart and tb treatment on cytokine/chemokine responses to mycobacterium tuberculosis (mtb) antigens in active tb patients and latently mtb infected individuals.identification of mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for tb. levels of ifn-γ, il-2, il-17, il-10, ip-10 and mip-1α were measured in supernatants of whole blood stimulated with mtb specific fusion protein esat-6/cfp-10 using xmap technology. the study groups were hiv positive tb patients (hiv(+)tb(+)), hiv negative tb patients (hiv(-)tb(+)), hiv positive tuberculin skin test positive (tst+) (hiv(+)t ...201626631832
evaluation of host hsp(s) as potential biomarkers for the diagnosis of tuberculous meningitis.diagnosis of tuberculosis meningitis (tbm) remains challenging in tuberculosis (tb) endemic countries. the need for tb biomarkers arises, in part, from the difficulty of accurately diagnosing tbm with the available methods.201626638081
isoniazid and rifampin drug susceptibility testing: application of 2,3,5-triphenyl tetrazolium chloride assay and microscopic-observation drug-susceptibility assay directly on ziehl-neelsen smear positive sputum specimens.the current study was aimed to evaluate the performance of direct 2,3,5-triphenyl tetrazolium chloride assay and direct microscopic observation drug susceptibility assay with indirect löwenstein-jensen proportion method directly on ziehl-neelsen smear positive sputum specimens.201626638012
evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of mycobacterium species, nocardia species, and other aerobic actinomycetes.the value of matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) for the identification of bacteria and yeasts is well documented in the literature. its utility for the identification of mycobacteria and nocardia spp. has also been reported in a limited scope. in this work, we report the specificity of maldi-tof ms for the identification of 162 mycobacterium species and subspecies, 53 nocardia species, and 13 genera (totaling 43 species) of other aerobic a ...201626637381
mycobacterium tuberculosis whib3 responds to vacuolar ph-induced changes in mycothiol redox potential to modulate phagosomal maturation and virulence.the ability of mycobacterium tuberculosis to resist intraphagosomal stresses, such as oxygen radicals and low ph, is critical for its persistence. here, we show that a cytoplasmic redox sensor, whib3, and the major m. tuberculosis thiol, mycothiol (msh), are required to resist acidic stress during infection. whib3 regulates the expression of genes involved in lipid anabolism, secretion, and redox metabolism, in response to acidic ph. furthermore, inactivation of the msh pathway subverted the exp ...201626637353
mycobacterium tuberculosis-specific cd4+ t-cell response is increased, and treg cells decreased, in anthelmintic-treated patients with latent tb.in many settings, adults with active or latent tuberculosis will also be coinfected with helminths. our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. we investigated the potential impact of helminth infection on immune responses to mycobacterium tuberculosis (mtb) in patients with latent mtb infection with or without helminth infection (strongyloides or schistosoma), and tested t-cell response ...201626638865
synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent.in search of new active molecules against mycobacterium tuberculosis (mtb) h37ra and m. bovis bcg, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. several derivatives were found to be promising inhibitors of mtb and m. bovis bcg characterized by lower mic values (27.34-29.37μg/ml). among all the synthesized compounds, 6c and 6e is the most active compound against mtb and m. bovis bcg. the compounds were further tested f ...201626642768
sfrp1 variations influence susceptibility and immune response to mycobacterium tuberculosis in a chinese han population.sfrp1 acts as a well-established inhibitory regulator of the wnt signaling pathway, whose polymorphisms have been demonstrated to be associated with the risk of inflammation, infection as well as cancer. we verified the hypothesis that single nucleotide polymorphisms (snps) within sfrp1 gene are associated with susceptibility and clinical characteristics of tuberculosis disease in a chinese han population.201626643984
synthesis and evaluation of antibacterial and antitumor activities of new galactopyranosylated amino alcohols.three series of d-galactose derivatives linked to a lipophilic aminoalcohol moiety were synthesized and their antibacterial activity was evaluated against mycobacterium tuberculosis and representative species of gram positive and gram negative bacteria. five out of the thirteen tested compounds displayed activity against m. tuberculosis, with a minimal inhibitory concentration (mic) of 12.5 μg/ml and seven compounds were active against the four bacterial strains tested. the best results were obt ...201626649907
polymorphisms in the pe35 and ppe68 antigens in mycobacterium tuberculosis strains may affect strain virulence and reflect ongoing immune evasion.previous studies have demonstrated that the pro‑glu/pro‑pro‑glu (pe/ppe) genes in strains of mycobacterium tuberculosis exhibit high sequence variation and may be involved in antigenic variation and immune evasion. region of difference 1 (rd1), encoding genes from rv3871 to rv3879, was observed to be lost during the original derivation of bacillus calmette‑guérin between 1908 and 1921. it has been previously demonstrated that two pe/ppe proteins, pe35 (rv3872) and ppe68 (rv3873), are encoded by ...201626648016
age- and sex-specific social contact patterns and incidence of mycobacterium tuberculosis infection.we aimed to model the incidence of infection with mycobacterium tuberculosis among adults using data on infection incidence in children, disease prevalence in adults, and social contact patterns. we conducted a cross-sectional face-to-face survey of adults in 2011, enumerating "close" (shared conversation) and "casual" (shared indoor space) social contacts in 16 zambian communities and 8 south african communities. we modeled the incidence of m. tuberculosis infection in all age groups using thes ...201626646292
synthesis and bioactivity of antitubercular peptides and peptidomimetics: an update.mycobacterium tuberculosis is the causative agent of tuberculosis (tb), an infection that has been declared a global public health emergency by the world health organization. current anti-tb therapies are limited in their efficacy and have failed to prevent the spread of tb, due to the long term drug compliance required and the genesis of multidrug-resistant strains (mdr). the number of chemotherapeutic agents currently available to treat mdr is limited, therefore there is a great need for new a ...201626645944
detection of mycobacterium tuberculosis genome in subretinal fluid of patients with latent tuberculosis infection.to test our hypothesis that mycobacterium tuberculosis (mtb) dna may be present in retinal pigment epithelium (rpe) cells in individuals with latent tuberculosis (tb) infection.201626645647
mycobacterium tuberculosis copper-regulated protein socb is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer.multiple genes in mycobacterium tuberculosis (mtb) are regulated by copper including socab (small orf induced by copper a and b), which is induced by copper and repressed by ricr (regulated in copper repressor). soca and socb encode hypothetical proteins of 61 and 54 amino acids, respectively. here, we use biophysical and computational methods to evaluate the socb structure. we find that socb lacks evidence for secondary structure, with no thermal cooperative unfolding event, according to circul ...201626650755
mannose-capped lipoarabinomannan from mycobacterium tuberculosis induces cd4+ t cell anergy via grail.mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit cd4(+) t cell activation by downregulating the phosphorylation of key proximal tcr signaling molecules: lck, cd3ζ, zap70, and lat. inhibition of proximal tcr signaling can result in t cell anergy, in which t cells are inactivated following an ag encounter, yet remain viable and hyporesponsive. we tested whether mannose-capped lipoarabinomannan (lam)-induced inhibition of cd4(+) t cell activation resulted in cd4(+) t ...201626667170
genetic diversity of the mycobacterium tuberculosis beijing family based on multiple genotyping profiles.among the most prevalent mycobacterium tuberculosis (mtb) strains worldwide is the beijing genotype, which has caused large outbreaks of tuberculosis (tb). characteristics facilitating the dissemination of beijing family strains remain unknown, but they are presumed to have been acquired through evolution of the lineage. to explore the genetic diversity of the beijing family mtb and explore the discriminatory ability of mycobacterial interspersed repetitive units-variable number of tandem repeat ...201626667080
inhibition of tlr8 mediated signaling promotes bcg induced apoptosis in thp-1 cells.apoptosis was considered as one of the important host defense mechanisms against mycobacteria infection. in macrophage, the main target cell of mycobacterium tuberculosis, apoptosis after infection could help kill the bacillus inside and process the antigens for further presentation and proper immune response. here, we identified a role of tlr8 during the apoptosis induced by bacillus calmette guérin (bcg) infection in thp-1 cells. knockdown tlr8 further increased the apoptosis induced by bcg in ...201626657720
electrochemical biosensor for mycobacterium tuberculosis dna detection based on gold nanotubes array electrode platform.the template assisted electrochemical deposition technique was used for the synthesis of gold nanotubes array (auntsa). the morphological structure of the synthesized auntsa was observed by scanning electron microscopy and found that the individual nanotubes are around 1.5 μm in length with a diameter of 200 nm. nanotubes are vertically aligned to the au thick film, which is formed during the synthesis process of nanotubes. the electrochemical performance of the auntsa was compared with the bare ...201626657592
rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: physicochemical and in vitro studies.systemic administration of antitubercular drugs can be complicated by off-target toxicity to cells and tissues that are not infected by mycobacterium tuberculosis . delivery of antitubercular drugs via nanoparticles directly to the infected cells has the potential to maximize efficacy and minimize toxicity. the present work demonstrates the potential of solid lipid nanoparticles (sln) as a delivery platform for rifabutin (rfb). two different rfb-containing sln formulations were produced using gl ...201626656946
single nucleotide polymorphisms in cytokine mif gene promoter region are closely associated with human susceptibility to tuberculosis in a southwestern province of china.the gene encoding macrophage migration inhibitory factor (mif) has been proposed as candidate tuberculosis (tb) susceptibility gene. in order to elucidate whether mif gene variants are associated with susceptibility to retreatment cases of tb, and prevent drug-resistant tb prevalence, we conducted a study based on paired human population data. mif -173 g/c single nucleotide polymorphisms (rs755622) were genotyped using polymerase chain reaction-restriction fragment length polymorphism. mif level ...201626656832
mycobacterium tuberculosis pe27 activates dendritic cells and contributes to th1-polarized memory immune responses during in vivo infection.a gradual understanding of the proline-glutamate (pe) and proline-proline-glutamate (ppe) families, which compromise 10% of the coding regions in the mycobacterium tuberculosis (mtb) genome, has uncovered unique roles in host-pathogen interactions. however, the immunological function of pe27 (rv2769c), the largest pe member, remains unclear. here, we explored the functional roles and related signaling mechanisms of pe27 in the interaction with dendritic cells (dcs) to shape the t cell response. ...201626655143
evaluation of molecular detection of extrapulmonary tuberculosis and resistance to rifampicin with genexpert® mtb/rif.we aimed to evaluate the genexpert® mtb/rif test for the diagnosis of extrapulmonary tuberculosis. the test simultaneously detects mycobacterium tuberculosis complex and resistance to rifampicin.201626654321
diagnostic usefulness of the genotype mtbdrplus assay for detecting drug-resistant tuberculosis using afb smear-negative specimens with positive tb-pcr result.the aim of this study was to evaluate the diagnostic accuracy of the genotype mtbdrplus assay in detecting drug-resistant tuberculosis (dr-tb) by using acid-fast bacilli (afb) smear-negative specimens with positive tb-pcr results.201626654187
synthesis of mycobacterium tuberculosis sulfolipid-3 analogues and total synthesis of the tetraacylated trehaloglycolipid of mycobacterium paraffinicum.a novel methodology for the regioselective o6 acylation of the 2,3-diacyl trehaloses to access mycobacterium tuberculosis sulfolipid sl-3 and related 2,3,6-triester glycolipid analogues is reported for the first time. the methodology was successfully extended to achieve the first total synthesis of the tetraacylated trehalose glycolipid from mycobacterium paraffinicum. the corresponding 2,3,6'-triesters trehalose glycolipids were also synthesized starting from the common 2,3-diacyl trehalose. th ...201626652194
pharmacokinetics and dosing of levofloxacin in children treated for active or latent multidrug-resistant tuberculosis, federated states of micronesia and republic of the marshall islands.in the federated states of micronesia and then the republic of the marshall islands (rmi), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies.201626658531
performance characteristics of the new abbott real time mtb assay for detection of mycobacterium tuberculosis complex in respiratory specimens.the performance of the abbott real time mtb assay for detection of mycobacterium tuberculosis complex in respiratory specimens was evaluated using a standard culture as the reference. the overall concordance between both methods was 0.95. the assay displayed an excellent sensitivity (100% for smear-positive/92.3% for smear-negative specimens) and specificity (100%).201626658312
implementation of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci in mycobacterium tuberculosis molecular epidemiology.this study shows that the addition of a consensus 4-locus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem repeat (miru-vntr) loci to the spoligotyping-24-locus miru-vntr typing strategy is a well-standardized approach that can contribute to an improvement of the true cluster definition while retaining high typeability in non-beijing strains.201626659207
structural and biochemical insight into the mechanism of rv2837c from mycobacterium tuberculosis as a c-di-nmp phosphodiesterase.the intracellular infections of mycobacterium tuberculosis, which is the causative agent of tuberculosis, are regulated by many cyclic dinucleotide signaling. rv2837c from m. tuberculosis is a soluble, stand-alone dhh-dhha1 domain phosphodiesterase that down-regulates c-di-amp through catalytic degradation and plays an important role in m. tuberculosis infections. here, we report the crystal structure of rv2837c (2.0 å), and its complex with hydrolysis intermediate 5'-papa (2.35 å). our structur ...201626668313
stereoselective alkylation of the vinylketene silyl n,o-acetal and its application to the synthesis of mycocerosic acid.stereoselective alkylation of the vinylketene silyl n,o-acetal possessing a chiral auxiliary has been achieved by using activated alkyl halides including allyl iodides, benzyl iodides, and propargyl iodide with ag(i) ion in the presence of bf3·oet2. the reaction proceeded to give reduced polyketides in high stereoselectivity. the synthesis of mycocerosic acid, a component of the cell envelope of mycobacterium tuberculosis, has been accomplished by this methodology. during the synthetic studies, ...201626673532
a rapid pcr assay to characterize the intact pks15/1 gene, a virulence marker in mycobacterium tuberculosis.intact pks15/1 is involved in the biosynthesis of phenolic glycolipids and proposed as a marker for virulence and phylogeny in tuberculosis. identification of intact condition is achieved mainly by dna sequencing. for this reason the aim of this study was to develop a reproducible endpoint pcr-assay to characterize it.201626672684
characterization of a novel esterase rv1497 of mycobacterium tuberculosish37rv demonstrating β-lactamase activity.the rv1497 (lipl) of the mycobacterium tuberculosis h37rv was predicted to be similar to hypothetical esterases and penicillin binding proteins ofm. tuberculosis as well as to be involved in lipid metabolism. sequence alignment revealed that rv1497 protein contains characteristic consensus β-lactamase motif 'sxxk' in addition to a conserve pentapeptide -gxsxg-, characteristic of lipolytic enzymes, at the c-terminus of protein in contrast to its usual n-terminus location. for detailed characteriz ...201626672466
intra-cavitary masses: rare presentation of a common illness in saarc nation.cardiovascular tuberculosis (tb) is a relatively uncommon manifestation of mycobacterium tuberculosis infection. tb can affect all three layers of the heart; endocardial tuberculoma is the rarest form. endocardial tuberculoma, when it occurs, can easily be confused with other common causes of intracardiac mass lesions, especially in echocardiography. timely diagnosis and appropriate treatment is essential, as only this can lessen the associated morbidity and mortality. here, a case of cardiovasc ...201626670207
rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study.slow and cumbersome laboratory diagnostics for mycobacterium tuberculosis complex (mtbc) risk delayed treatment and poor patient outcomes. whole-genome sequencing (wgs) could potentially provide a rapid and comprehensive diagnostic solution. in this prospective study, we compare real-time wgs with routine mtbc diagnostic workflows.201626669893
whole-genome sequencing of mycobacterium tuberculosis for rapid diagnostics and beyond. 201626669892
identification of a novel class of quinoline-oxadiazole hybrids as anti-tuberculosis agents.a series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. the hybrid compounds synthesized were screened for biological activity against mycobacterium tuberculosis h37rv and for cytotoxicity in hepg2 cell line. several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed ...201626675440
the stimulating role of subunit f in atpase activity inside the a1-complex of the methanosarcina mazei gö1 a1ao atp synthase.a1ao atp synthases couple ion-transport of the ao sector and atp synthesis/hydrolysis of the a3b3-headpiece via their stalk subunits d and f. here, we produced and purified stable a3b3d- and a3b3df-complexes of the methanosarcina mazei gö1 a-atp synthase as confirmed by electron microscopy. enzymatic studies with these complexes showed that the m. mazei gö1 a-atp synthase subunit f is an atpase activating subunit. the maximum atp hydrolysis rates (vmax) of a3b3d and a3b3df were determined by sub ...201626682760
high levels of anti-tuberculin (igg) antibodies correlate with the blocking of t-cell proliferation in individuals with high exposure to mycobacterium tuberculosis.to determine the effect of anti-tuberculin antibodies in the t-cell proliferation in response to tuberculin and candida antigens in individuals with different levels of tuberculosis (tb) risk.201626686942
an orphaned mce-associated membrane protein of mycobacterium tuberculosis is a virulence factor that stabilizes mce transporters.mycobacterium tuberculosis proteins that are exported out of the bacterial cytoplasm are ideally positioned to be virulence factors; however, the functions of individual exported proteins remain largely unknown. previous studies identified rv0199 as an exported membrane protein of unknown function. here, we characterized the role of rv0199 in m. tuberculosis virulence using an aerosol model of murine infection. rv0199 appears to be a member of a mce-associated membrane (mam) protein family leadi ...201626712165
new insights into the survival mechanisms of rifampicin-resistant mycobacterium tuberculosis.rifampicin is considered the most important antibiotic for treating tb, but unfortunately mycobacterium tuberculosis is rapidly developing resistance to this drug. despite the fervent research efforts to date, tb is still a major global problem, and hence new approaches are necessary to better characterize this disease, especially the mechanisms relating to drug resistance.201626679254
what defines latent infection with mycobacterium tuberculosis in patients with autoimmune diseases? 201626678433
replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? mycobacterium tuberculosis novel bacterial topoisomerase inhibitors.recently numerous non-fluoroquinolone-based bacterial type ii topoisomerase inhibitors from both the gyra and gyrb classes have been reported as antibacterial agents. inhibitors of the gyra class include aminopiperidine-based novel bacterial type ii topoisomerase inhibitors (nbtis). however, inhibition of the cardiac ion channel remains a serious liability for the aminopiperidine based nbtis. in this paper we replaced central aminopiperidine linker with piperazine moiety and tested for its biolo ...201626678175
paradoxical anti-tnf-associated tb worsening: frequency and factors associated with iris.paradoxical tuberculosis (tb) worsening, an example of the immune reconstitution inflammatory syndrome (iris), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (tnf) discontinuation during biotherapy-induced tb. to better recognize it, we analyzed the frequency and factors associated with anti-tnf-induced tb-iris.201626677996
sensitivity of c-tb: a novel rd-1-specific skin test for the diagnosis of tuberculosis infection.c-tb, a novel mycobacterium tuberculosis and 6-kda early secretory antigenic target/10-kda culture filtrate protein (esat-6/cfp-10)-specific skin test, has high specificity in bacille calmette-guerin-vaccinated healthy controls. however, the sensitivity of c-tb has hitherto not been determined. the objective was to determine the sensitivity of c-tb in patients with active tuberculosis (tb) in comparison with the tuberculin skin test (tst) and quantiferon-tb gold in-tube (qft-git).c-tb and tst we ...201626677940
mycobacterium tuberculosis h37rv infected thp-1 cells induce epithelial mesenchymal transition (emt) in lung adenocarcinoma epithelial cell line (a549).chronic infections of mycobacterium tuberculosis (mtb) cause oxidative stress, tlr activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. in present study, we have shown for the first time that mtb infection in human monocytic cell line (thp-1) enhances invasion and induce ...201626677761
udp-glcnac pathway: potential target for inhibitor discovery against m. tuberculosis.in the past five years, an alarming increase in the number of patients with multidrug resistant tuberculosis (mdr tb) and extensively drug-resistant tuberculosis (xdr tb) has been reported, particularly in eastern europe, asia and southern africa. current situation has challenged the control and treatment of tuberculosis (tb) which sparked an emergent need to find new anti-tubercular agents with different chemical scaffolds and mechanisms of action. a very fruitful way to identify novel anti-tub ...201626690048
increased risk of latent tuberculous infection among persons with pre-diabetes and diabetes mellitus.although diabetes mellitus (dm) is an established risk factor for active tuberculosis (tb) disease, little is known about the association between pre-dm, dm, and latent tuberculous infection (ltbi).201626688531
mortality after anti-tuberculosis treatment completion: results of long-term follow-up.mycobacterium tuberculosis affects the lung parenchyma even after successful treatment.201626688527
clinical implications of molecular drug resistance testing for mycobacterium tuberculosis: a tbnet/resist-tb consensus statement.the emergence of drug-resistant strains of mycobacterium tuberculosis is a challenge to global tuberculosis (tb) control. although culture-based methods have been regarded as the gold standard for drug susceptibility testing (dst), molecular methods provide rapid information on mutations in the m. tuberculosis genome associated with resistance to anti-tuberculosis drugs. we ascertained consensus on the use of the results of molecular dst for clinical treatment decisions in tb patients. this docu ...201626688526
plan beta for tuberculosis: it's time to think seriously about poorly ventilated congregate settings.globally, the rates of decline in tuberculosis (tb) incidence are disappointing, but in line with model predictions regarding the likely impact of the dots strategy. here, we review evidence from basic epidemiology, molecular epidemiology and modelling, all of which suggest that, in high-burden settings, the majority of mycobacterium tuberculosis transmission may occur in indoor congregate settings. we argue that mass environmental modifications in these places might have a significant impact on ...201626688524
in vitro time-kill curves study of three antituberculous combinations against mycobacterium tuberculosis clinical isolates.the objective of this study was to examine the in vitro synergism of three-drug combinations against mycobacterium tuberculosis (levofloxacin/linezolid/ethambutol, levofloxacin/amikacin/ethambutol and levofloxacin/linezolid/amikacin) using the time-kill curves method. in total, 8 multidrug-resistant and 12 drug-susceptible m. tuberculosis isolates were used. minimum inhibitory concentrations (mics) of the isolates for each drug were determined by the proportions method. time-kill curves were stu ...201626691020
major loci on chromosomes 8q and 3q control interferon γ production triggered by bacillus calmette-guerin and 6-kda early secretory antigen target, respectively, in various populations.interferon γ (ifn-γ) release assays (igras) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for mycobacterium tuberculosis infection. igra outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown.201626690346
discovery of bicyclic inhibitors against menaquinone biosynthesis.menaquinone is used for transporting electrons and is essential for the aerobic and anaerobic respiratory systems of all pathogens and prokaryotes. many gram-positive bacteria use only menaquinone in the electron transport system. thus, menaquinone biosynthesis is a potential target for the development of inhibitors against bacteria including drug-resistant pathogens.201626699277
modified tb rapid test by proteinase k for rapid diagnosis of pleural tuberculosis.the diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional diagnostic methods. better and more rapid tests are needed for diagnosis of pleural tb. in this study, pleural fluids were tested with rapid test to determine mycobacterium tuberculosis (mtb antigen). affinity chromatography was used to purify specific polyclonal antibodies against mtb antigen. pleural samples after decontamination were treated with proteinase k. rapid test for pleural flu ...201626693840
a multistate tuberculosis pharmacometric model: a framework for studying anti-tubercular drug effects in vitro.mycobacterium tuberculosis can exist in different states in vitro, which can be denoted as fast multiplying, slow multiplying and non-multiplying. characterizing the natural growth of m. tuberculosis could provide a framework for accurate characterization of drug effects on the different bacterial states.201626702921
reactive oxygen species production by human dendritic cells involves tlr2 and dectin-1 and is essential for efficient immune response against mycobacteria.tuberculosis remains the single largest infectious disease with 10 million new cases and two million deaths that are estimated to occur yearly, more than any time in history. the intracellular replication of mycobacterium tuberculosis (mtb) and its spread from the lungs to other sites occur before the development of adaptive immune responses. dendritic cells (dc) are professional antigen-presenting cells whose maturation is critical for the onset of the protective immune response against tubercu ...201626709456
adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings.adenosine deaminase (ada) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (ptb) in high tuberculosis prevalence settings. we investigated the diagnostic utility of pleural ada using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with ptb, 70 with other diagnoses) were analy ...201626707067
design, synthesis and bioactivity evaluation of galf mimics as antitubercular agents.a series of novel galf mimics has been synthesized and characterized by ir, (1)h nmr, (13)c nmr, mass spectral and element analysis. all the newly prepared compounds were screened for their antitubercular activities. bioactivity assays manifested that most of galf mimics exhibited good antitubercular activities. especially compound 4d and 4e displayed remarkable antitubercular efficacies, which were comparable to ethambutol.201626706033
interferon-gamma release assay versus tuberculin skin test for latent tuberculosis infection among hiv patients in brazil.patients hiv+ attending in a reference clinic, southern brazil.201626706018
antitubercular lanostane triterpenes from cultures of the basidiomycete ganoderma sp. bcc 16642.sixteen new lanostane triterpenoids (1-16), together with 26 known compounds (17-42), were isolated from cultures of the basidiomycete ganoderma sp. bcc 16642. antitubercular activities of these ganoderma lanostanoids against mycobacterium tuberculosis h37ra were evaluated, and structure-activity relationships are proposed.201626716912
pulmonary responses to pathogen-specific antigens in latent mycobacterium tuberculosis infection.in this study, we used elispot to quantify frequencies of bronchoalveolar lavage (bal) and peripheral blood t cells capable of producing ifnγ in response to ppd, antigen 85b, and mtb-specific antigens cfp-10 and esat-6 in individuals with latent tuberculosis infection (ltbi) and mtb-naïve controls. compared to peripheral blood, bal cells of ltbi subjects displayed significant enrichment for t cells responding to ppd, antigen 85b, and cfp-10, but not to esat-6. baseline bal cells of ltbi subjects ...201626732045
host-directed therapy targeting the mycobacterium tuberculosis granuloma: a review.infection by the intracellular bacterial pathogen mycobacterium tuberculosis (mtb) is a major cause of morbidity and mortality worldwide. slow progress has been made in lessening the impact of tuberculosis (tb) on human health, especially in parts of the world where mtb is endemic. due to the complexity of tb disease, there is still an urgent need to improve diagnosis, prevention, and treatment strategies to control global spread of disease. active research targeting avenues to prevent infection ...201626510950
crystal structure of mycobacterium tuberculosis o6-methylguanine-dna methyltransferase protein clusters assembled on to damaged dna.mycobacterium tuberculosis o(6)-methylguanine-dna methyltransferase (mtogt) contributes to protect the bacterial gc-rich genome against the pro-mutagenic potential of o(6)-methylated guanine in dna. several strains of m. tuberculosis found worldwide encode a point-mutated o(6)-methylguanine-dna methyltransferase (ogt) variant (mtogt-r37l), which displays an arginine-to-leucine substitution at position 37 of the poorly functionally characterized n-terminal domain of the protein. although the impa ...201626512127
time-resolved studies of isdg protein identify molecular signposts along the non-canonical heme oxygenase pathway.isdgs are heme monooxygenases that break open the tetrapyrrole, releasing the iron, and thereby allowing bacteria expressing this protein to use heme as a nutritional iron source. little is currently known about the mechanism by which isdgs degrade heme, although the products differ from those generated by canonical heme oxygenases. a synthesis of time-resolved techniques, including in proteo mass spectrometry and conventional and stopped-flow uv/visible spectroscopy, was used in conjunction wit ...201626534961
design, synthesis, and antimycobacterial activity of novel theophylline-7-acetic acid derivatives with amino acid moieties.the theophylline-7-acetic acid (7-taa) scaffold is a promising novel lead compound for antimycobacterial activity. here, we derive a model for antitubercular activity prediction based on 14 7-taa derivatives with amino acid moieties and their methyl esters. the model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-taa. the best three predicted compounds are synthesized and tested against mycobacterium tuberculosis h37rv. all of them are stable ...201626502828
structural insight into dihydrodipicolinate reductase from corybebacterium glutamicum for lysine biosynthesis.dihydrodipicolinate reductase is an enzyme that converts dihydrodipicolinate to tetrahydrodipicolinate using an nad(p)h cofactor in l-lysine biosynthesis. to increase the understanding of the molecular mechanisms of lysine biosynthesis, we determined the crystal structure of dihydrodipicolinate reductase from corynebacterium glutamicum (cgdapb). cgdapb functions as a tetramer, and each protomer is composed of two domains, an nterminal domain and a c-terminal domain. the n-terminal domain mainly ...201626502738
microrna 17-5p regulates autophagy in mycobacterium tuberculosis-infected macrophages by targeting mcl-1 and stat3.autophagy plays a crucial role in the control of bacterial burden during mycobacterium tuberculosis infection. micrornas (mirnas) are small non-coding rnas that regulate immune signalling and inflammation in response to challenge by pathogens. appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the role of mirnas in regulating m. tuberculosis-induced autophagy in macrophages. here, we demonstrate that m. tuberculosis i ...201626513648
construction of au-ide/cfp10-esat6 aptamer/dna-aunps mspqc for rapid detection of mycobacterium tuberculosis.au-ide/cfp10-esat6 aptamer/dna-aunps mspqc for rapid detection of mycobacterium tuberculosis was constructed based on specific detection of specific fused antigen cfp10-esat6 which secreted only by pathogenic m. tuberculosis in its early culture time. cfp10-esat6 aptamer was used as sensor specific probe of cfp10-esat6 antigen. au nanoparticles (nps) was employed to increase sensor senstivity. the au-ide/cfp10-esat6 aptamer/dna-aunps electrode probe was prepared by modifying of the complementary ...201626513286
a case of empyema necessitatis in a child with mycobacterium tuberculosis. 201626519294
ifn-γ and iga against non-methylated heparin-binding hemagglutinin as markers of protective immunity and latent tuberculosis: results of a longitudinal study from an endemic setting.heparin-binding hemagglutinin (hbha) is a surface protein involved in epithelial attachment and extrapulmonary dissemination of mycobacterium tuberculosis. hbha is attracting increasing attention for its vaccine and diagnostic potential. in a longitudinal study, we investigated non-methylated, recombinant hbha-specific cytokine and antibody profiles in cohorts of tb patients, their contacts and community controls in an endemic setting.201626518056
d-alanine metabolism is essential for growth and biofilm formation of streptococcus mutans.part of the d-alanine (d-ala) metabolic pathway in bacteria involves the conversion of l-alanine to d-ala by alanine racemase and the formation of d-alanyl-d-alanine by d-alanine-d-alanine ligase, the product of which is involved in cell wall peptidoglycan synthesis. at present, drugs that target the metabolic pathway of d-ala are already in clinical use - e.g. d-cycloserine (dcs) is used as an antibiotic against mycobacterium tuberculosis. streptococcus mutans is the main cariogenic bacterium i ...201626526529
game of 'somes: protein destruction for mycobacterium tuberculosis pathogenesis.the proteasome system of mycobacterium tuberculosis is required for causing disease. proteasomes are multisubunit chambered proteases and, until recently, were only known to participate in adenosine triphosphate (atp)-dependent proteolysis in bacteria. in this review, we discuss the latest advances in understanding how both atp-dependent and atp-independent proteasome-regulated pathways contribute to m. tuberculosis virulence.201626526503
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