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efficacy of serum chitotriosidase activity in early treatment of patients with active tuberculosis and a negative sputum smear.the results of sputum culture for mycobacterium tuberculosis must be awaited in most cases, which delays the start of treatment in patients with sputum smear-negative pulmonary tuberculosis. we investigated whether plasma chitotriosidase activity is a strong marker for early diagnosis of tuberculosis in patients for whom a bacillus smear is negative and tuberculosis culture is positive.201222956876
a simple recipe for the non-expert bioinformaticist for building experimentally-testable hypotheses for proteins with no known homologs.the study of the protein-protein interactions (ppis) of unique orfs is a strategy for deciphering the biological roles of unique orfs of interest. for uniform reference, we define unique orfs as those for which no matching protein is found after pdb-blast search with default parameters. the uniqueness of the orfs generally precludes the straightforward use of structure-based approaches in the design of experiments to explore ppis. many open-source bioinformatics tools, from the commonly-used to ...201222956349
structural basis for benzothiazinone-mediated killing of mycobacterium tuberculosis.the benzothiazinone btz043 is a tuberculosis drug candidate with nanomolar whole-cell activity. btz043 targets the dpre1 catalytic component of the essential enzyme decaprenylphosphoryl-β-d-ribofuranose-2'-epimerase, thus blocking biosynthesis of arabinans, vital components of mycobacterial cell walls. crystal structures of dpre1, in its native form and in a complex with btz043, reveal formation of a semimercaptal adduct between the drug and an active-site cysteine, as well as contacts to a neig ...201222956199
evaluation of coa biosynthesis proteins of mycobacterium tuberculosis as potential drug targets.coenzyme a biosynthesis pathway proteins are potential targets for developing inhibitors against bacteria including mycobacterium tuberculosis. we have evaluated two enzymes in this pathway: phosphopantetheine adenylyltransferase (coad) and dephospho coa kinase (coae) for essentiality and selectivity. based on the previous transposon mutagenesis studies, coad had been predicted to be a non-essential gene in m. tuberculosis. our bioinformatics analysis showed that there is no other functional hom ...201222954585
miru-vntr analysis of the mycobacterium tuberculosis isolates from three provinces of iran.iran borders 2 high-burden tuberculosis (tb) countries to the east, and has the highest rates of tb in one of its eastern provinces. limited information is available on the genetic diversity and transmission dynamics of mycobacterium tuberculosis (mtb) in iran. to examine the genetic diversity and transmission dynamics of mtb strains we genotyped a collection of isolates from different parts of iran.201322954102
activity of trifluoperazine against replicating, non-replicating and drug resistant m. tuberculosis.trifluoperazine, a known calmodulin antagonist, belongs to a class of phenothiazine compounds that have multiple sites of action in mycobacteria including lipid synthesis, dna processes, protein synthesis and respiration. the objective of this study is to evaluate the potential of tfp to be used as a lead molecule for development of novel tb drugs by showing its efficacy on multiple drug resistant (mdr) mycobacterium tuberculosis (m.tb) and non-replicating dormant m.tb. wild type and mdr m.tb we ...201222952939
rv2190c, an nlpc/p60 family protein, is required for full virulence of mycobacterium tuberculosis.mycobacterium tuberculosis, the etiologic agent of tuberculosis (tb) possesses at least five genes predicted to encode proteins with nlpc/p60 hydrolase domains, including the relatively uncharacterized rv2190c. as nlpc/p60 domain-containing proteins are associated with diverse roles in bacterial physiology, our objective was to characterize rv2190c in m. tuberculosis growth and virulence. our data indicate that lack of rv2190c is associated with impaired growth, both in vitro and during an in vi ...201222952680
dominant incidence of multidrug and extensively drug-resistant specific mycobacterium tuberculosis clones in osaka prefecture, japan.infection and transmission of multidrug-resistant mycobacterium tuberculosis (mdr-mtb) and extensively drug-resistant m. tuberculosis (xdr-mtb) is a serious health problem. we analyzed a total of 1,110 mtb isolates in osaka prefecture and neighboring areas from april 2000 to march 2009. a total of 89 mdr-mtb were identified, 36 (48.5%) of which were determined to be xdr-mtb. among the 89 mdr-mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspers ...201222952596
anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.a 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. a chest radiograph showed diffuse infiltration in the right lung field. laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. a kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of igg along the glomerular basement membrane (gbm). circulating igg anti-gbm antibody was not detected. because the findings of renal biopsy suggeste ...201222950833
cosubstrate tolerance of the aminoglycoside resistance enzyme eis from mycobacterium tuberculosis.we previously demonstrated that aminoglycoside acetyltransferases (aacs) display expanded cosubstrate promiscuity. the enhanced intracellular survival (eis) protein of mycobacterium tuberculosis is responsible for the resistance of this pathogen to kanamycin a in a large fraction of clinical isolates. recently, we discovered that eis is a unique aac capable of acetylating multiple amine groups on a large pool of aminoglycoside (ag) antibiotics, an unprecedented property among aac enzymes. here, ...201222948873
synthesis and antitubercular activity evaluation of novel unsymmetrical cyclohexane-1,2-diamine derivatives.a library of unsymmetrical cyclohexane-1,2-diamine derivatives were synthesized and evaluated for their activity against mycobacterium tuberculosis h37rv in vitro. out of the 46 compounds synthesized, eight compounds (11h, 13a, 13e, 13f, 14a, 14c, 14d, and 15d) were found to be active at or below 6.25 µm concentration, with negligible toxicity to human red blood cells at a concentration much higher than the mic(99) . compound 13a was the best active compound showing inhibition at 3.125-6.25 µm, ...201222945019
functional characterization of the mycobacterium tuberculosis zinc metallopeptidase zmp1 and identification of potential substrates.zinc metallopeptidases of bacterial pathogens are widely distributed virulence factors and represent promising pharmacological targets. in this work, we have characterized zmp1, a zinc metallopeptidase identified as a virulence factor of mycobacterium tuberculosis and belonging to the neprilysin (nep; m13) family, whose x-ray structure has been recently solved. interestingly, this enzyme shows an optimum activity toward a fluorogenic substrate at moderately acidic ph values (i.e., 6.3), which co ...201222944667
drug resistance-conferring mutations in mycobacterium tuberculosis from madang, papua new guinea.monitoring drug resistance in mycobacterium tuberculosis is essential to curb the spread of tuberculosis (tb). unfortunately, drug susceptibility testing is currently not available in papua new guinea (png) and that impairs tb control in this country. we report for the first time m. tuberculosis mutations associated with resistance to first and second-line anti-tb drugs in madang, png. a molecular cluster analysis was performed to identify m. tuberculosis transmission in that region.201222943573
cyanovirin-n inhibits mannose-dependent mycobacterium-c-type lectin interactions but does not protect against murine tuberculosis.cyanovirin-n (cv-n) is a mannose-binding lectin that inhibits hiv-1 infection by blocking mannose-dependent target cell entry via c-type lectins. like hiv-1, mycobacterium tuberculosis expresses mannosylated surface structures and exploits c-type lectins to gain cell access. in this study, we investigated whether cv-n, like hiv-1, can inhibit m. tuberculosis infection. we found that cv-n specifically interacted with mycobacteria by binding to the mannose-capped lipoglycan lipoarabinomannan. furt ...201222942435
mycobacterium tuberculosis prokaryotic ubiquitin-like protein-deconjugating enzyme is an unusual aspartate amidase.deamidase of pup (dop), the prokaryotic ubiquitin-like protein (pup)-deconjugating enzyme, is critical for the full virulence of mycobacterium tuberculosis and is unique to bacteria, providing an ideal target for the development of selective chemotherapies. we used a combination of genetics and chemical biology to characterize the mechanism of depupylation. we identified an aspartate as a potential nucleophile in the active site of dop, suggesting a novel protease activity to target for inhibito ...201222942282
comprehensive analysis of methods used for the evaluation of compounds against mycobacterium tuberculosis.in drug development, there are typically a series of preclinical studies that must be completed with new compounds or regimens before use in humans. a sequence of in vitro assays followed by in vivo testing in validated animal models to assess the activity against mycobacterium tuberculosis, pharmacology and toxicity is generally used for advancing compounds against tuberculosis in a preclinical stage. a plethora of different assay systems and conditions are used to study the effect of drug cand ...201222940006
three new 12-carbamoylated streptothricins from streptomyces sp. i08a 1776.two new streptothricins (1 and 2) and a new streptothricin acid derivative (3), all with the carbamoyl group substituted at c-12 of the gulosamine moiety, together with the known n(β)-acetylstreptothricin d acid (4), have been isolated from the culture broth of streptomyces sp. i08a 1776. the structures of the new compounds were determined by ms, cd, and 1d and 2d nmr spectroscopic data analysis. the isolated compounds were evaluated for antibacterial and antifungal activities. streptothricin e ...201222939698
polymorphisms in the promoter of the cd14 gene and their associations with susceptibility to pulmonary tuberculosis.although the role of cd14 in recognizing mycobacterium tuberculosis is well-understood, the possible role of polymorphisms in susceptibility to develop tuberculosis remains unclear. this study evaluates whether there is an association of polymorphisms within the promoter of the cd14 gene with susceptibility to pulmonary tuberculosis. in a case-control study, we genotyped the eight known single nucleotide polymorphisms snps within the promoter of the cd14 gene of 698 han chinese subjects. statist ...201222937756
interaction of mycobacterium tuberculosis rsha and sigh is mediated by salt bridges.the alternate sigma factor sigh of mycobacterium tuberculosis is expressed under stress and acts as a major regulator of several genes, including some other sigma factors and redox systems. while it is auto-regulated by its own promoter at the transcriptional level, its regulation at the post-translational level is through its cognate protein, an anti-sigma factor, rsha. hither before rsha was believed to be a zinc-associated anti-sigma factor (zas) and the binding of rsha to sigh is redox depen ...201222937074
survey of the diagnostic retooling process in national tb reference laboratories, with special focus on rapid speciation tests endorsed by who in 2007.successful integration of new diagnostics in national tuberculosis (tb) control programs, also called 'retooling', is highly dependent on operational aspects related to test availability, accessibility and affordability. this survey aimed to find out whether recommendations to use new diagnostics lead to successful retooling in high tb endemic countries, using immunochromatographic tests (icts) for tb culture speciation as a case study. icts are recommended to accurately confirm the presence of ...201222937050
clonal expansion of both modern and ancient genotypes of mycobacterium tuberculosis in southern taiwan.we present the first comprehensive analysis of mycobacterium tuberculosis isolates circulating in the kaohsiung region of southern taiwan. the major spoligotypes found in the 224 isolates studied were beijing lineages (n = 97; 43.3%), eai lineages (n = 72; 32.1%) and haarlem lineages (n = 18; 8.0%). by 24 miru-vntr typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. the combination of spoligotyping and 12-miru-vntr revealed that 129 (57.6%) of the ...201222937008
adherence to and outcome of isoniazid chemoprophylaxis among household contact children of adults having pulmonary tuberculosis in alexandria, egypt.current international guidelines recommend 6-9 months of isoniazid (inh) preventive chemotherapy to prevent the development of active tuberculosis (tb) in susceptible children exposed to mycobacterium tuberculosis. however, this is dependent on good adherence, as shown by previous studies.201222936243
paradoxical mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an hiv-infected child.immune reconstitution inflammatory syndrome occurs in a subset of hiv-infected individuals as the immune system recovers secondary to antiretroviral therapy. an exaggerated and uncontrolled inflammatory response to antigens of viable or nonviable organisms is characteristic, with clinical deterioration despite improvement in laboratory indicators. we describe a fatal case of mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an hiv-infected child and review the ...201322935867
etiology of community-acquired pneumonia in hospitalized children in northern taiwan.pneumonia is the leading reason for hospitalization in children. the heptavalent pneumococcal conjugate vaccine was introduced in taiwan in october 2005. there has been no comprehensive study of the etiology of childhood community-acquired pneumonia (cap), either in the pre- or postpneumococcal conjugate vaccine era, in taiwan.201222935863
gene expression profiling of tuberculous meningitis co-infected with hiv.tuberculous meningitis (tbm) is a fatal form of mycobacterium tuberculosis infection of the central nervous system (cns). the similarities in the clinical and radiological findings in tbm cases with or without hiv make the diagnosis very challenging. identification of genes, which are differentially expressed in brain tissues of hiv positive and hiv negative tbm patients, would enable better understanding of the molecular aspects of the infection and would also serve as an initial platform to ev ...201227053842
epidemic of tuberculosis in a high school in northern sardinia.the aim of this study was to investigate the mycobacterium tuberculosis transmission among high school student and teacher populations in a high school in northern sardinia. tuberculin skin-test screening, chest-x-rays, quantiferon-tb gold, microbiological examination, spoligotyping and variable numbers of tandem repeats (vntr) analysis of m. tuberculosis isolates were performed. this study indicates the effectiveness of the epidemiological investigation.201226787215
retrieval of mycobacterium tuberculosis cultures suspended in phosphate buffered saline.one hundred and twenty-seven of 130 isolates of mycobacterium tuberculosis, suspended in phosphate buffered saline (pbs) and stored at ambient conditions in the laboratory for 14days, and another 55 of 60 cultures, suspended as above, transported from reference laboratories within 7days, were successfully retrieved on lj medium. considering the maximum retrieval of m. tuberculosis, use of pbs can be explored further for transportation of m. tuberculosis cultures across laboratories.201226787212
identification of mycobacterium tuberculosis complex by polymerase chain reaction of exact tandem repeat-d fragment from mycobacterial cultures.this study evaluated an in-house polymerase chain reaction (pcr) for rapid identification of the mycobacterium tuberculosis complex (mtbc) using the mtbc-specific exact tandem repeat d (etr-d) as the amplification target. in a prospective study, 801 clinical isolates identified as mtbc and 15 nontuberculous mycobacteria were analyzed. mycobacterial dna was extracted from automated broth cultures or from egg-based media. the amplification of the etr-d showed to a sensitivity of 99.6% and a specif ...201226787211
performance indicators of fluorescence microscopy for sputum samples in pulmonary tuberculosis.to get insight into the sensitivity of fluorescence microscopy for diagnostic and follow-up sputum samples from pulmonary tuberculosis patients in clinical trials, the yield of smear positivity - among culture positive sputum samples - encountered in diagnostic and follow-up samples was retrospectively analyzed from the data available in a mycobacteriology laboratory in india. the sensitivity of fluorescence microscopy for diagnostic and follow-up samples respectively was found to be 94.3% and 6 ...201226787210
risk factors for multidrug-resistant tuberculosis in urban pakistan: a multicenter case-control study.to evaluate risk factors for multidrug-resistant tuberculosis (mdr-tb) in an urban setting of pakistan.201226787209
multidrug and extensively drug-resistant tuberculosis in lisbon and vale do tejo, portugal, from 2008 to 2010.tuberculosis (tb) was explicitly recognized as a major global public health problem in the early 1990s and, if it is to be eliminated, it is essential that every country organize control activities in line with its own epidemiological situation. portugal still remains among the countries with intermediate incidence, with 2756 cases of tb diagnosed in 2009. the incidence of multidrug-resistant (mdr) tb has been decreasing, representing an average of 1.7% of the total number of tb cases, with abou ...201226787208
drug resistance-related mutations in multidrug-resistant mycobacterium tuberculosis isolates from diverse geographical regions.drug resistance in mycobacterium tuberculosis is associated with chromosomal mutations in selected genes. these mutations can be screened for an early warning system for drug-resistant tuberculosis. the prevalence of individual mutations differs geographically, which must be considered in developing globally applicable screening tests.201226787207
multidrug resistant mycobacterium tuberculosis amongst category i & ii failures and category ii relapse patients from pakistan.to determine the prevalence of multidrug-resistant tuberculosis (mdr-tb) among previously treated tb patients in khyber pakhtunkhwa (kp) province, pakistan.201226787206
division-cycle in mycobacterium tuberculosis. 201226787205
incidence of multidrug resistance in mycobacterium tuberculosis in a tertiary care hospital in south india--a prospective study.multidrug resistant tuberculosis (mdr-tb) is one worrisome element in this era of pandemic antibiotic resistance. this demands a need for diagnosis, and incidence of primary and acquired resistance to help in better management. smear positive respiratory samples collected over a period of one year were processed for detection of m. tuberculosis, using biochemical methods and susceptibility to p-nitro benzoic acid. finally, strains detected by the above method were subjected to susceptibility for ...201225145062
prevalence of non-tuberculous mycobacterium in a tertiary care hospital from south india.tuberculosis is a wide spread infectious disease all over the world as well as in india. other than tuberculosis complex, more than 30 different non-tuberculous mycobacteria (ntm) are responsible for various diseases, i.e. cervical lymphadelopathy, cutaneous abscess, pulmonary diseases, post-operative infections, etc. these ntms are resistant to commonly used antimicrobial and anti-tubercular agents, jeopardizing the dots and dots plus program in the country. the accurate diagnosis of mycobacter ...201225145059
recent advances in the diagnosis of mycobacterium tuberculosis.molecular technologies offer the greatest potential for laboratories in resource-rich countries because they have the highest sensitivity and specificity. continued use of new technologies will be crucial in elucidating the true epidemiology and pathogenesis of a disease, including the less well studied diseases. continued development of affordable, sensitive, and specific diagnostic tools will be required for use in resource-poor settings, where the incidence of disease is highest.201224432271
russian "successful" clone b0/w148 of mycobacterium tuberculosis beijing genotype: a multiplex pcr assay for rapid detection and global screening.we describe a multiplex pcr assay to detect the mycobacterium tuberculosis beijing genotype variant b0/w148, which is considered a "successful" clone of m. tuberculosis, widespread in russia. specificity and sensitivity of the assay were 100% based on the analysis of a collection of 516 m. tuberculosis isolates of different genotypes and origins. this assay may be used for accurate and simple detection and surveillance of this clinically and epidemiologically important variant of m. tuberculosis ...201222933595
hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.one of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. a small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. a commonly used screening protocol used for this task is high-throughput screening (hts). however, the performance of hts against antibacterial targets has generally been unsatisfactory, with high costs and ...201222933186
[sequence analysis on drug-resistant gene of rpob in mdr-tb among pneumoconiosis patients complicated with tuberculosis in huainan mining district].to study the characteristics of drug-resistant genetic mutation of rpob in multiple drugs resistant bacillus tuberculosis (mdr-tb) among patients of pneumoconiosis complicated with pulmonary tuberculosis.201222931875
[advances in research for resistance mechanisms of aminoglycoside and cyclic peptide antibiotic to mycobacterium tuberculosis]. 201222931808
identification of less lipophilic riminophenazine derivatives for the treatment of drug-resistant tuberculosis.clofazimine (cfz), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (mdr-tb). cfz has several side effects which can be attributed to its extremely high lipophilicity. a series of novel riminophenazine analogues bearing a c-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against mycobacterium tuberculosis (m. tuberculosis) while improving upon its safety profile by lowe ...201222931472
prevalence of pulmonary tuberculosis among hiv infected persons in pokhara, nepal.tuberculosis (tb) is a major public health problem in nepal. hiv co-infection has further added a serious challenge to control tb. an early diagnosis and treatment of tb in hiv infected individuals can help reduce not only the morbidity and mortality associated in this high risk group but also to control the tb burden in nepal.201222929634
computational genomics-proteomics and phylogeny analysis of twenty one mycobacterial genomes (tuberculosis & non tuberculosis strains). 201222929624
synthesis and evaluation of a selective fluorogenic pup derived assay reagent for dop, a potential drug target in mycobacterium tuberculosis.a litter of pups: the synthesis and in vitro evaluation of new pup-based fluorogenic substrates for dop, the mycobacterial depupylase, are described. a full-length pup-amidomethylcoumarin conjugate as well as an amino-terminus-truncated analogue exhibited high sensitivity and specificity towards hydrolysis by dop. the substrates developed here might find application as high-throughput screening assay reagents for the identification of dop inhibitors.201222927162
mannose-capped lipoarabinomannan from mycobacterium tuberculosis induces soluble tumor necrosis factor receptor production through tumor necrosis factor alpha-converting enzyme activation.primary mycobacterium tuberculosis infection results in granuloma formation in lung tissue. a granuloma encapsulates mycobacterium-containing cells, thereby preventing dissemination and further infection. tumor necrosis factor alpha (tnf-α) is a host-protective cytokine during m. tuberculosis infection due to its role in promoting and sustaining granuloma formation. tnf activity is regulated through the production of soluble tnf receptors (stnfri and stnfrii). therefore, we examined the potentia ...201222927046
new onset diabetes in a patient with active tuberculosis.the present report describes the coincidence of pulmonary tuberculosis (tb) and metabolic disorder such as diabetes. a patient's bronchoalveolar lavage was found to be positive for acid-fast bacilli (afb) with following growth of mycobacterium tuberculosis and complete sensitivity to first line anti-tb drugs. at the same time, the patient presented with typical diabetes manifestation and subsequently required insulin therapy. combined treatment resulted in significant clinical improvement and gr ...201222926909
in vitro combination studies of benzothiazinone lead compound btz043 against mycobacterium tuberculosis.benzothiazinones (btz) are a new class of drug candidates to combat tuberculosis that inhibit decaprenyl-phosphoribose epimerase (dpre1), an essential enzyme involved in arabinan biosynthesis. using the checkerboard method and cell viability assays, we have studied the interaction profiles of btz043, the current lead compound, with several antituberculosis drugs or drug candidates against mycobacterium tuberculosis strain h37rv, namely, rifampin, isoniazid, ethambutol, tmc207, pa-824, moxifloxac ...201222926573
influence of vehicles used for oral dosing of test molecules on the progression of mycobacterium tuberculosis infection in mice.preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. we studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of mycobacterium tuberculosis infection in mice. infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. compared with water, corn oil significantly improved both set ...201222926571
streptomycin-starved mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis.mycobacterium tuberculosis 18b, a streptomycin (str)-dependent mutant that enters a viable but nonreplicating state in the absence of str, has been developed as a simple model for drug testing against dormant bacilli. here, we further evaluated the str-starved 18b (ss18b) model both in vitro and in vivo by comparing the behavior of 22 approved and experimental tuberculosis drugs. using the resazurin reduction microplate assay (rema), rifampin (rif), rifapentine (rpt), tmc207, clofazimine (cfm), ...201222926567
influence of htlv-1 on the clinical, microbiologic and immunologic presentation of tuberculosis.htlv-1 is associated with increased susceptibility to mycobacterium tuberculosis infection and severity of tuberculosis. although previous studies have shown that htlv-1 infected individuals have a low frequency of positive tuberculin skin test (tst) and decreasing in lymphoproliferative responses compared to htlv-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of m. tuberculosis infection. therefore the reasons why htlv-1 infection ...201222925731
human phagosome processing of mycobacterium tuberculosis antigens is modulated by interferon-γ and interleukin-10.intracellular pathogens, such as mycobacterium tuberculosis, reside in the phagosomes of macrophages where antigenic processing is initiated. mycobacterial antigen-mhc class ii complexes are formed within the phagosome and are then trafficked to the cell surface. interferon-γ (ifn-γ) and interleukin-10 (il-10) influence the outcome of m. tuberculosis infection; however, the role of these cytokines with regard to the formation of m. tuberculosis peptide-mhc-ii complexes remains unknown. we analys ...201322924705
bcg-specific igg-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in hiv negative and hiv positive patients.diagnosis of active tuberculosis (tb) among sputum-negative cases, patients with hiv infection and extra-pulmonary tb is difficult. in this study, assessment of bcg-specific igg-secreting peripheral plasmablasts, was used to identify active tb in these high-risk groups.201322923457
the mechanism of redox sensing in mycobacterium tuberculosis.tuberculosis epidemics have defied constraint despite the availability of effective treatment for the past half-century. mycobacterium tuberculosis, the causative agent of tb, is continually exposed to a number of redox stressors during its pathogenic cycle. the mechanisms used by mtb to sense redox stress and to maintain redox homeostasis are central to the success of mtb as a pathogen. careful analysis of the mtb genome has revealed that mtb lacks classical redox sensors such as fnr, fixl, and ...201222921590
synthesis and anti-tubercular activity of novel alkyl substituted riminophenazine derivatives.a series of novel riminophenazine derivatives bearing an alkyl substituent attached to n-5 and imino nitrogen at c-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. all target compounds were prepared by utilizing simple and flexible synthetic route and evaluated against mycobacterium tuberculosis h37rv and screened for mammalian cytotoxicity. the results demonstrated that compoun ...201222919722
acid-fast bacilli other than mycobacteria in tuberculosis patients receiving directly observed therapy short course in cross river state, nigeria.the information on the contribution of non tuberculous mycobacteria (ntm) to mycobacterial infections in africa is scarce due to limited laboratory culture for its isolation and identification. one hundred and thirty-seven sputum smear positive patients were recruited into a study on the molecular epidemiology of mycobacterium tuberculosis in cross river state. following sputum culture, 97 pure isolates were obtained and identified using capilia tb-neo and further confirmed by the genotype mycob ...201222919477
ischemic colitis during interferon-ribavirin therapy for chronic hepatitis c: a case report.ischemic colitis is a rare complication of interferon administration. only 9 cases in 6 reports have been described to-date. this report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis c, and includes a review of the relevant literature. a 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis c, genotype ib. after 19 wk of treatment, the patient complained of severe afebrile abdominal pain w ...201222919260
tuberculosis diagnostics: challenges and opportunities.tuberculosis (tb) has been a disease affecting almost all parts of the world since ages. lot many efforts came in the past for improving diagnosis and treatment. also, an effective vaccine has been sought after for long. with the emergence of resistant strains of mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. be it the better m ...201222919166
drug resistance profiles of mycobacterium tuberculosis isolates to first line anti-tuberculous drugs: a five years study.drug resistance is a major problem in the treatment of tuberculosis (tb). an estimate of drug resistance is extremely important in the epidemiology and control of tb. however, an assessment of the magnitude of drug resistance in tb is not very well described globally and data remains scantier for india. in view of this, we reviewed our data over last five years.201222919160
specific function of the met-tyr-trp adduct radical and residues arg-418 and asp-137 in the atypical catalase reaction of catalase-peroxidase katg.catalase activity of the dual-function heme enzyme catalase-peroxidase (katg) depends on several structural elements, including a unique adduct formed from covalently linked side chains of three conserved amino acids (met-255, tyr-229, and trp-107, mycobacterium tuberculosis katg numbering) (myw). mutagenesis, electron paramagnetic resonance, and optical stopped-flow experiments, along with calculations using density functional theory (dft) methods revealed the basis of the requirement for a rad ...201222918833
oral immunogenicity of potato-derived antigens to mycobacterium tuberculosis in mice.the novel use of transgenic plants as vectors for the expression of viral and bacterial antigens has been increasingly tested as an alternative methodology for the production and delivery of experimental oral vaccines. here, we examined the immunogenicity of combined plant-made vaccines that include four genes encoding immune-dominant antigens from mycobacterium tuberculosis. compared with the wild type and other control groups, mice treated with the combined plant-made vaccines showed significa ...201222917938
combined species identification, genotyping, and drug resistance detection of mycobacterium tuberculosis cultures by mlpa on a bead-based array.the population structure of mycobacterium tuberculosis is typically clonal therefore genotypic lineages can be unequivocally identified by characteristic markers such as mutations or genomic deletions. in addition, drug resistance is mainly mediated by mutations. these issues make multiplexed detection of selected mutations potentially a very powerful tool to characterise mycobacterium tuberculosis. we used multiplex ligation-dependent probe amplification (mlpa) to screen for dispersed mutations ...201222916230
modern lineages of mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages.strains of mycobacterium tuberculosis vary in virulence. strains that have caused outbreaks in the united states and united kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. there is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of m. tuberculosis.201222916219
[specific spondylitis].tuberculosis of the spine usually occurs with a latency period after primary infection with tuberculosis (tb) and the most frequent agent is mycobacterium tuberculosis. the rate of tb has increased due to the impact of acquired immunodeficiency syndrome (aids) and more than 50% of skeletal tuberculosis is localized in the spine. spinal tuberculosis was discovered by pott in 1776. magnetic resonance imaging (mri) with gadolineum is the most sensitive imaging method. diagnostic accuracy is given b ...201222914915
reduced frequency of memory t cells and increased th17 responses in patients with active tuberculosis.phenotypic and functional alterations in mycobacterium tuberculosis t cell subsets have been reported in patients with active tuberculosis. a better understanding of these alterations will increase the knowledge about immunopathogenesis and also may contribute to the development of new diagnostics and prophylactic strategies. here, the ex vivo phenotype of cd4(+) and cd8(+) t cells and the frequency and phenotype of gamma interferon (ifn-γ)- and interleukin 17 (il-17)-producing cells elicited in ...201222914361
the first synthesis of an epidiselenodiketopiperazine.epidithiodiketopiperazines (etps) are natural products (e.g., gliotoxin) with varied and important biological activity, which often is attributed to the redox properties of the disulfide moiety. as such, analogs with altered redox properties and similar structural characteristics would be of value to biological investigations. the use of an etp as the point of departure in the first synthesis of an epidiselenodiketopiperazine (esep) and its activity against mycobacterium tuberculosis (mtb) is re ...201222913407
risk stratification of latent tuberculosis defined by combined interferon gamma release assays.most individuals infected with mycobacterium tuberculosis develop latent tuberculosis infection (ltbi). some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. here, we provide an approach to stratify ltbi based on ifn-γ responses to two antigens, the recombinant early-secreted antigen target-6 (resat-6) and the latency antigen heparin-binding haemagglutinin (hbha).201222912846
increased transmission of mycobacterium tuberculosis beijing genotype strains associated with resistance to streptomycin: a population-based study.studies have shown that the mycobacterium tuberculosis beijing genotype is an emerging pathogen that is frequently associated with drug resistance. this suggests that drug resistant beijing strains have a relatively high transmission fitness compared to other drug-resistant strains.201222912700
mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent il-1β and il-18 secretion but not to pyroptosis.interleukin-1β (il-1β) is important for host resistance against mycobacterium tuberculosis (mtb) infections. the response of the dendritic cell inflammasome during mtb infections has not been investigated in detail.201222911706
tuberculosis testing among populations with high hiv risk in tijuana, baja california, mexico.to assess the prevalence of prior tuberculin skin testing (tst) among populations at risk for hiv infection in tijuana, mexico, and to identify factors associated with tst.201222910722
skin biopsy: a pillar in the identification of cutaneous mycobacterium tuberculosis infection.the present study aimed to establish the frequency and clinical characteristics of cutaneous tuberculosis among mexican adult patients.201222910569
early secretory antigenic target-6 of mycobacterium tuberculosis: enigmatic factor in pathogen-host interactions.t helper (th) 1 and 17 cells play important roles in host protective responses against tuberculosis. early secretory antigenic target 6; a region of difference 1 (rd1) encoded protein, mounts th17-responses in the lung. therefore, lack of rd-1 region makes bacillus calmette-guérin (bcg) less vaccine efficacious than parent strains.201222909901
tubercular sclerouveitis masquerading as an ocular tumor: a case report.to report the diagnosis of a case of tubercular sclerouveitis, which masqueraded as an ocular tumor.201222909287
early control of mycobacterium tuberculosis infection requires il12rb1 expression by rag1-dependent lineages.il12rb1 is essential for human resistance to mycobacterium tuberculosis infection. in the absence of a functional il12rb1 allele, individuals exhibit susceptibility to disseminated, recurrent mycobacterial infections that are associated with defects in both rag1-dependent and rag1-independent hematopoietic lineages. despite this well-established association, a causal relationship between m. tuberculosis susceptibility and il12rb1 deficiency in either rag1-dependent or rag1-independent lineages h ...201222907814
protective efficacy of a recombinant bcg secreting antigen 85b/rv3425 fusion protein against mycobacterium tuberculosis infection in mice.in this study, the protective efficacy of a novel recombinant bcg strain co-expressing ag85b and rv3425 against mycobacterium tuberculosis h37rv was evaluated in mice. this rbcg::ag85b-rv3425 strain could provide similar or even better protective efficacy against m. tuberculosis challenge compared with bcg, as shown by no weight loss, significantly reduced lung:body weight ratios and lung bacteria load only at early time of infection. the results suggest that rbcg::ag85b-rv3425 could be a potent ...201222906934
meropenem inhibits d,d-carboxypeptidase activity in mycobacterium tuberculosis.carbapenems such as meropenem are being investigated for their potential therapeutic utility against highly drug-resistant tuberculosis. these β-lactams target the transpeptidases that introduce interpeptide cross-links into bacterial peptidoglycan thereby controlling rigidity of the bacterial envelope. treatment of mycobacterium tuberculosis (mtb) with the β-lactamase inhibitor clavulanate together with meropenem resulted in rapid, polar, cell lysis releasing cytoplasmic contents. in mtb it has ...201222906310
value of the tuberculin skin testing and of an interferon-gamma release assay in haemodialysis patients after exposure to m. tuberculosis.patients with end-stage renal disease (esrd) and mycobacterium tuberculosis infection pose a high risk of developing active tb disease. it is therefore important to detect latent tb infection (ltbi) to be able to offer treatment and prevent progression to tb disease. we assessed the value of the tuberculin skin test (tst) and of an interferon-gamma release assay (quantiferon®-tb gold in-tube, qft) for diagnosing ltbi in esrd patients, after prolonged exposure to a highly contagious tb case in a ...201222905901
detection of is6110 and hupb gene sequences of mycobacterium tuberculosis and bovis in the aortic tissue of patients with takayasu's arteritis.takayasu's arteritis (ta) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. in individuals suffering from ta, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. relation of ta with mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. the is6110 sequence identifies the mycobacterium tuberculosis complex an ...201222905864
detonation nanodiamonds for rapid detection of clinical isolates of mycobacterium tuberculosis complex in broth culture media.routinely used molecular diagnostic methods for mycobacterium identification are expensive and time-consuming. to tackle this problem, we develop a method to streamline identification of mycobacterium tuberculosis complex (mtbc) in broth culture media by using detonation nanodiamonds (dnds) as a platform to effectively capture the antigen secreted by mtbc which is cultured in bactec mgit 960, followed by the analysis of matrix-assisted laser desorption/ionization mass spectrometry (maldi-tof ms) ...201222905748
performance characteristics of the cepheid xpert mtb/rif test in a tuberculosis prevalence survey.xpert mtb/rif ("xpert") is a molecular test for detection of mycobacterium tuberculosis (mtb) in sputum. performance characteristics have been established for its use during passive tuberculosis (tb) case detection in symptomatic tb suspects, but xpert performance has not been assessed in other settings. objectives were to determine xpert performance and costs in the context of a tb prevalence survey.201222905254
early secreted antigenic target of 6-kda protein of mycobacterium tuberculosis primes dendritic cells to stimulate th17 and inhibit th1 immune responses.early secreted antigenic target of 6 kda (esat-6) of mycobacterium tuberculosis is a t cell ag that is a potential vaccine candidate, but it is also a virulence factor that mediates pathogenicity. to better understand the effects of esat-6 on the immune response, we studied the effect of esat-6 on human dendritic cells (dcs). peripheral blood monocytes were treated with gm-csf and il-4 to yield immature dcs, which were matured by addition of lps and cd40 ligand (cd40l), with or without esat-6. e ...201222904313
a modified acid-fast staining method for rapid detection of mycobacterium tuberculosis.a modified acid-fast staining method was developed for rapid detection of mycobacterium tuberculosis and its l forms, wherein carbol fuchsin and dioxogen were mixed into the sputum smear. with this method, the dyeing time is shortened and heating is not required. the sensitivity, specificity, positive predictive value, negative predictive value, positive rate, and diagnostic efficiency of the new method were compared to those obtained by pcr using 50 clinical samples. further, 468 clinical sampl ...201222902528
diagnosis of tuberculosis infection based on synthetic peptides from mycobacterium tuberculosis antigen 85 complex.the laboratory diagnosis of pulmonary tuberculosis (tb) and tuberculous meningitis (tbm) is particularly challenging. the aim of the present work is to develop an immunoassay for the diagnosis of tb infection, using synthetic peptides of antigen (ag) 85 complex of m. tuberculosis (mtb) h37rv.201322902080
extracellular m. tuberculosis dna targets bacteria for autophagy by activating the host dna-sensing pathway.eukaryotic cells sterilize the cytosol by using autophagy to route invading bacterial pathogens to the lysosome. during macrophage infection with mycobacterium tuberculosis, a vacuolar pathogen, exogenous induction of autophagy can limit replication, but the mechanism of autophagy targeting and its role in natural infection remain unclear. here we show that phagosomal permeabilization mediated by the bacterial esx-1 secretion system allows cytosolic components of the ubiquitin-mediated autophagy ...201222901810
detection and confirmation of alkaloids in leaves of justicia adhatoda and bioinformatics approach to elicit its anti-tuberculosis activity.the extraction and determination of alkaloids was performed and confirmed by phytochemical analysis. six different quinazoline alkaloids (vasicoline, vasicolinone, vasicinone, vasicine, adhatodine and anisotine) were found in the leaf of justicia adhatoda (j. adhatoda). the presence of the peaks obtained through hplc indicated the diverse nature of alkaloid present in the leaf. the enzyme β-ketoacyl-acyl-carrier protein synthase iii that catalyses the initial step of fatty acid biosynthesis (fab ...201222899014
molecular dynamics simulation of the last step of a catalytic cycle: product release from the active site of the enzyme chorismate mutase from mycobacterium tuberculosis.the protein chorismate mutase mtcm from mycobacterium tuberculosis catalyzes one of the few pericyclic reactions known in biology: the transformation of chorismate to prephenate. chorismate mutases have been widely studied experimentally and computationally to elucidate the transition state of the enzyme catalyzed reaction and the origin of the high catalytic rate. however, studies about substrate entry and product exit to and from the highly occluded active site of the enzyme have to our knowle ...201222898919
[retrospective study of dysfunction transplant nephrectomy from a single-center within 10 years].to find the reasons for dysfunction in renal graft.201222898849
syntheses of mycobactin analogs as potent and selective inhibitors of mycobacterium tuberculosis.three analogs of mycobactin t, the siderophore secreted by mycobacterium tuberculosis (mtb) were synthesized and screened for their antibiotic activity against mtb h(37)rv and a broad panel of gram-positive and gram-negative bacteria. the synthetic mycobactins were potent (mic(90) 0.02-0.88 μm in 7h12 media) and selective mtb inhibitors, with no inhibitory activity observed against any other of the microorganisms tested. the maleimide-containing analog 40 represents a versatile platform for the ...201222895786
gene sequencing for routine verification of pyrazinamide resistance in mycobacterium tuberculosis: a role for pnca but not rpsa.pyrazinamide (pza) is an important component of first-line therapy for the treatment of tuberculosis. here, we evaluate targeted gene sequencing as a supplement to phenotypic pza susceptibility testing of mycobacterium tuberculosis. routine sequencing of pnca, but not rpsa, is effective for verification of pza susceptibility results.201222895038
evaluation of the sensititre mycotb plate for susceptibility testing of the mycobacterium tuberculosis complex against first- and second-line agents.the sensititre mycotb plate (trek diagnostic systems, cleveland, oh) uses a microtiter plate mic format for susceptibility testing of mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. categorical agreement versus the agar proportion method for 122 m. tuberculosis complex isolates was 94% to 100%.201222895034
the preparation of hl-60 cells vaccine expressing bcg heat shock protein 70 and detection of its immunogenicity in vitro.gene-modified cell vaccines are the best way to achieve the immunotherapy for all types of acute leukemia. in this study, the recombinant eukaryotic expression vector (pdisplay-hsp70) of heat shock protein 70 (hsp70) of bacille calmette-guérin (bcg) was constructed by amplifying the whole bcg hsp70 gene using polymerase chain reaction (pcr) and sub-cloning into the polyclone endonuclease sites in pdisplay. then the hl-60 cell vaccine expressing the protein onto the cell surface was prepared by l ...201222894947
synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents.a new series of 5-fluoro-n(2)-(cyclohexylidene)-3-phenyl-1h-indole-2-carbohydrazides (6a-6e) and their cyclization products 5-fluoro-n-(3-oxo-1-thia-4-azaspiro [4.5]dec-4-yl)-3-phenyl-1h-indole-2-carboxamides (7a-7e, 8a-8e) have been synthesized and evaluated for in vitro antimycobacterial activity against mycobacterium tuberculosis h37rv using the microplate alamar blue assay (maba). compounds showed moderate to good inhibitory activity at 6.25 μg/ml. among them, 7b, 7d, 8b, and 8d were the mos ...201222893206
protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of cd4(+) /cd4(+)  foxp3(+) cells.cd4(+) foxp3(+) regulatory t cells inhibit the production of interferon-γ, which is the major mediator of protection against mycobacterium tuberculosis infection. in this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory t cells. we observed that after homologous immunization with the 65 000 molecular weight heat-shock protein (hsp 65) dna vaccine, there was a significantly higher num ...201222891805
therapeutic immunization against mycobacterium tuberculosis is an effective adjunct to antibiotic treatment.recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. the aim of this study was to assess whether therapeutic immunization could impact the course of mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, id93, formulated in a synthetic nanoemulsion adjuvant, gla-se, administered in combination with existing first-line chemotherapeutics rifampicin and ...201322891286
application of fragment screening and merging to the discovery of inhibitors of the mycobacterium tuberculosis cytochrome p450 cyp121. 201222890978
drug susceptibility pattern of mycobacterium tuberculosis isolates from patients of category-ii failure of pulmonary tuberculosis under directly observed treatment short-course from north india.the major contributing factors for the causation of treatment failure in cases of pulmonary tuberculosis under category-ii directly observed treatment short-course treatment (dots) are treatment after default, poor treatment compliance, and development of multi-drug resistant (mdr) tuberculosis. the objective of the present study is to find out the demographic profile and drug susceptibility pattern in category-ii failure patients of pulmonary tuberculosis under revised national tuberculosis con ...201222890158
development and characterization of ligand-appended liposomes for multiple drug therapy for pulmonary tuberculosis.tuberculosis (tb) remains one of the oldest and deadliest diseases in the current scenario. the intracellular organism mycobacterium tuberculosis, which mainly resides in mononuclear phagocytes, is responsible for tuberculosis in humans. a few therapies are available for the treatment of tuberculosis but they have many hurdles. to overcome these hurdles, a combination of chemotherapeutic agent-loaded vesicular systems have been prepared to overcome tuberculosis. to investigate the role of novel ...201322889361
6-hydrogen-8-methylquinolones active against replicating and non-replicating mycobacterium tuberculosis.the screening of an in-house quinolones library against mycobacterium tuberculosis (mtb) h(37) rv, followed by a first cycle of optimization, yielded 6-hydrogen-8-methyl derivatives endowed with good potency. the antitubercular activity also encompassed the bacteria in a non-replicating state (nrp-tb) with minimum inhibitory concentration values lower than those of the reference agent, moxifloxacin. among the best compounds, 11w and 11ai, characterized by a properly substituted piperidine at the ...201222889240
differential induction of macrophage cell death by antigens of a clustered and a non-clustered multidrug-resistant mycobacterium tuberculosis strain from haarlem family.some multidrug-resistant (mdr) mycobacterium tuberculosis (mtb) genotypes are the cause of large outbreaks, including strain m identified in argentina. in contrast, its kin strain 410 has only caused a single case to date. cell wall antigens from mtb were associated with the modulation of macrophage (mφ) cell death, and the ability to inhibit of mφ apoptosis is considered a virulence mechanism. in this study, the ability these two clinical isolates with divergent epidemiology to induce mφ cell d ...201222889125
molecular logic gates for dna analysis: detection of rifampin resistance in m. tuberculosis dna.elementary, dr. watson! a combination of yes and or logic gates was applied to differentiate between dna sequences of wild-type and rifampin-resistant (rif(r)) mycobacterium tuberculosis (mtb) in a multiplex real-time fluorescent assay.201222888076
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