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bridging the gap between pcr detection of mycobacterium tuberculosis complex and tuberculosis diagnosis.the growing demand for rapid diagnosis of tuberculosis (tb) has led to the incorporation of nucleic acid amplification (naa) tests in case definitions. the objective of this study was to evaluate the contribution of a real-time polymerase chain reaction (pcr) assay in providing a result predictive of a confirmed tb case. respiratory and extra-pulmonary specimens (n = 308) were subjected to naa, culture and smear microscopy. qualitative pcr assessment, translated by an increase in naa cycles, dis ...201222230008
human mycobacterium bovis infection in buenos aires: epidemiology, microbiology and clinical presentation.we performed a retrospective study of clinical, epidemiological and microbiological characteristics of patients with confirmed mycobacterium bovis infection treated at francisco muñiz hospital, buenos aires, argentina, between 1996 and 2008. a total of 39 patients were included, accounting for 0.4% of tuberculosis cases in our hospital. of these, 93% had at least one risk factor form. bovis; the most frequent was occupational exposure (65%), followed by history of living in a rural area (31%) an ...201222230360
mass spectrometry based methods for the discrimination and typing of mycobacteria.identification and typing of mycobacteria is very important for epidemiology, susceptibility testing and diagnostic purposes. this paper describes the development and validation of the alternative methods for species identification and typing of mycobacteria based on a matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (maldi-tof ms). altogether there were 383 clinical isolates analyzed which include 348 strains of mycobacterium tuberculosis complex (mtbc) (342 strains ...201122230718
predictors of 5-year mortality in pulmonary mycobacterium avium-intracellulare complex disease.setting: kyoto, japan.objective: to determine predictors of 5-year mortality in pulmonary mycobacterium avium-intracellulare complex (mac) disease.design: retrospective study of 164 patients diagnosed with pulmonary mac disease between 1999 and 2005 and followed for 5 years.results: overall 5-year mortality was 28.0%. among 117 patients with microbiological outcomes, 54 were treated (treated mac patients) and 24 were not treated and did not experience sputum culture conversion during follow-up ( ...201222230733
lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in mycobacterium tuberculosis.to measure molecular changes underlying pathogen adaptation, we generated a searchable dataset of more than 12,000 mass spectrometry events, corresponding to lipids and small molecules that constitute a lipidome for mycobacterium tuberculosis. iron is essential for m. tuberculosis survival, and the organism imports this metal using mycobactin and carboxymycobactin siderophores. detection of an unexpected siderophore variant and deletions of genes for iron scavenging has led to a revised mycobact ...201222232695
different potency of bacterial antigens, both tlr2 and tlr4 ligands, in stimulating mature mast cells to cysteinyl leukotriene synthesis.the aim of study was to compare the potency of different bacterial antigens to induce rat mature mast cell to cysteinyl leukotriene (cyslt) generation. we examined toll-like receptor (tlr)2 agonists, i.e. lipoteichoic acid (lta) staphylococcus faecalis, streptococcus pyogenes, bacillus subtilis and staphylococcus aureus, lipoarabinomannan (lam) mycobacterium smegmatis, peptydoglican (pgn) staphylococcus aureus, as well as tlr4 agonists, i.e. lipopolysaccharide (lps) klebsiella pneumoniae, pseudo ...201222233438
[peritoneal tuberculosis in a patient with suspected disseminated ovarian cancer.]we present a case study of a 43 year-old female immigrant from turkey with abdominal pain, ascites and elevated cancer antigen 125. the symptoms were similar to those of ovarian cancer, and imaging (computed tomography (ct), positron emission tomography/computed tomography and magnetic resonance imaging) supported this suspicion. peritoneal biopsy from laparoscopy showed granulomas with central necrosis. microscopy, culture and polymerase chain reaction from biopsy samples were negative for myco ...201222233724
deciphering the genetic architecture of variation in the immune response to mycobacterium tuberculosis infection.tuberculosis (tb) is a major public health problem. one-third of the world's population is estimated to be infected with mycobacterium tuberculosis (mtb), the etiological agent causing tb, and active disease kills nearly 2 million individuals worldwide every year. several lines of evidence indicate that interindividual variation in susceptibility to tb has a heritable component, yet we still know little about the underlying genetic architecture. to address this, we performed a genome-wide mappin ...201222233810
the stress-response factor sigh modulates the interaction between mycobacterium tuberculosis and host phagocytes.the mycobacterium tuberculosis stress response factor sigh plays a crucial role in modulating the pathogen's response to heat, oxidative-stress, envelope damage and hypoxia. we hypothesized that the lack of this key stress response factor would alter the interaction between the pathogen and its host cells. we compared the interaction of mtb, mtb:δ-sigh and a strain where the mutation had been genetically complemented (mtb: δ-sigh:co) with primary rhesus macaque bone marrow derived macrophages (r ...201222235255
low dose aerosol fitness at the innate phase of murine infection better predicts virulence amongst clinical strains of mycobacterium tuberculosis.evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active tb has been set by assuming that this is linked to the fitness of mycobacterium tuberculosis strain at the innate phase of the infection. thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active tb, once the adaptive response is set.201222235258
in vitro antimycobacterial activity and hplc-dad screening of phenolics from ficus benjamina l. and ficus luschnathiana (miq.) miq. leaves.the total phenolic content (folin-ciocalteu) of the leaves of ficus benjamina and ficus luschnathiana was evaluated and screened by hplc-dad. ficus luschnathiana crude extract (ce) presented phenolic content higher than that of f. benjamina (149.92 ± 3.65 versus 122.63 ± 2.79 mg of gae). kaempferol (1.63 ± 0.16 mg g(-1) dry weight of ce) and chlorogenic acid (17.77 ± 0.57 mg g(-1) of butanolic fraction) were identified and quantified in f. benjamina, whereas rutin (1.39 ± 0.20 mg g(-1)), caffeic ...201222235967
rifampicin-monoresistant mycobacterium tuberculosis disease among children in cape town, south africa.tygerberg children's hospital (tch) and brooklyn chest hospital (bch), south africa.201222236850
patterns of pnca mutations in drug-resistant mycobacterium tuberculosis isolated from patients in south korea.pyrazinamide (pza), one of the most effective anti-tuberculosis drugs, becomes toxic to mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (pzase). pza resistance is caused mainly by the loss of enzyme activity by mutation.201222236853
real-time pcr and amplified mtd® for rapid detection of mycobacterium tuberculosis in pulmonary specimens.patients with suspected pulmonary tuberculosis (ptb) in the first affiliated hospital, college of medicine, zhejiang university.201222236926
evaluation of gamma interferon (ifn-γ)-induced protein 10 (ip-10) responses for detection of cattle infected with mycobacterium bovis: comparisons to ifn-γ responses.gamma interferon (ifn-γ)-induced protein 10 (ip-10) has recently shown promise as a diagnostic biomarker of mycobacterium tuberculosis infection of humans. the aim of the current study was to compare ip-10 and ifn-γ responses upon mycobacterium bovis infection in cattle using archived samples from two aerosol inoculation studies. in the first study (10(4) cfu m. bovis by aerosol, n = 7), m. bovis purified protein derivative (ppdb)-specific ip-10 and ifn-γ gene expression were detected as early a ...201222237891
[pulmonary aspergillosis complicating atypical mycobacterial infection in two patients suffering from chronic obstructive pulmonary disease].atypical mycobacteria and aspergillus are opportunistic organisms responsible for severe pulmonary diseases whose development is encouraged by the presence of chronic obstructive pulmonary disease (copd) and related immunosuppression.201222240225
resistance patterns of mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in nairobi.in kenya, which ranks thirteenth of 27 high tuberculosis burden countries, diagnosis is based on ziehl-neelsen staining alone and patients are treated without information on sensitivity patterns. this study aimed to determine resistance patterns of mycobacterium tuberculosis isolated from pulmonary samples.201222240426
evaluation of conventional molecular diagnosis of mycobacterium tuberculosis in clinical specimens from morocco.tuberculosis is a major public health threat, annually affecting new individuals worldwide, especially those in developing countries. rapid detection of the agent and effective treatment are two important factors in controlling this disease.201222240427
improved detection of mycobacterium tuberculosis using two independent pcr targets in a tertiary care centre in south india.tuberculosis (tb) causes significant morbidity and mortality worldwide as one of the leading infectious diseases. in india, more than 1.8 million new cases occur every year. rapid and accurate diagnosis of tb would improve patient care and limit its transmission. this study aimed to evaluate a dual target polymerase chain reaction (pcr) diagnostic assay to detect mycobacterium tuberculosis from pulmonary and extra-pulmonary samples at a tertiary care centre in south india.201222240428
the mcp-1 (ccl2) -2518 gg genotype is associated with protection against pulmonary tuberculosis in moroccan patients.both monocyte chemoattractant protein-1 (mcp-1), also designated officially as chemokine (c-c motif) ligand 2 (ccl2), and interleukin-12 p40 (il-12 p40) molecules, encoded by polymorphic genes, are central components of the immune response to infection by mycobacterium tuberculosis (mtb). their genetic diversity has previously been associated with the outcome of tuberculosis (tb) infection. we investigated whether the mcp-1 -2518 a/g and the il-12b (p40) +1188 a/c polymorphisms influence suscept ...201222240432
investigation of the levels of oxidative stress parameters in hiv and hiv-tb co-infected patients.among opportunistic pathogens associated with acquired immunodeficiency syndrome (aids), mycobacterium tuberculosis is distinguished by its relative virulence and potential for person-to-person transmission. oxidative stress is associated with tb infection with a high level in patients with hiv-tb co-infection. however, the comparative level of oxidative stress in hiv patients on highly active anti-retroviral therapy (haart) and naïve (untreated) hiv patients is not clear.201222240433
clinical and radiological deterioration due to mycobacterium szulgai in an asthmatic patient.we report the case of a 23-year-old asthmatic woman who had clinical and radiological deterioration due to mycobacterium szulgai infection and good response to anti-mycobacterial treatment without any structural abnormalities in previous lung imaging studies. m. szulgai may be considered a pathogen able to cause deterioration of respiratory health even in patients with previously normal lungs.201222240435
role of mycobacterium tuberculosis pknd in the pathogenesis of central nervous system tuberculosis.abstract: background: central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. though recent clinical reports suggest an association of distinct mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously. results: we screened 398 unique m. tuberculosis mutants in guinea pigs to identify genes required for central nervous ...201222243650
occurrence of mycobacterium avium subsp. paratuberculosis in milk at dairy cattle farms: a systematic review and meta-analysis.presence of mycobacterium avium subsp. paratuberculosis (map) in milk for human consumption is a concern due to its possible relationship with crohn's disease in humans. pasteurization effectively reduces the map load by four to five logs, but the efficacy depends on the map concentration, which depends on the prevalence among contributing herds and individuals. considerable variation of map in bulk tank milk (btm) and individual cow's milk (im) is reported, but factors associated with map occur ...201122245166
respiratory outbreak of mycobacterium abscessus subspecies massiliense in a lung transplant and cystic fibrosis center. 201222246710
conserved mechanisms of mycobacterium marinum pathogenesis within the environmental amoeba, acanthamoeba castellanii.mycobacterium marinum is a water-borne mycobacterial pathogen. due to their common niche, protozoa likely represent natural hosts for m. marinum. we demonstrate that the esx-1 secretion system is required for m. marinum pathogenesis and that m. marinum utilizes actin-based motility in amoebae. therefore, at least two virulence pathways used by m. marinum in macrophages are conserved during m. marinum infection of amoeba.201222247144
occurrence, diagnosis, and strain typing of mycobacterium avium subspecies paratuberculosis infection in rocky mountain bighorn sheep (ovis canadensis canadensis) in southwestern alberta.the role that wildlife may play in the transmission of mycobacterium avium subspecies paratuberculosis (map), the causative agent of johne's disease (jd), and the potential consequences of infection in these populations are being given increasing consideration. a yearling male rocky mountain bighorn sheep (ovis canadensis canadensis) from southwestern alberta, canada, was found infected with map in august 2009. clinical signs of emaciation and diarrhea and histologic findings of diffuse granulom ...201222247368
computed tomography of children with pulmonary mycobacterium tuberculosis infection.surveillance and control of tuberculous infection in pediatric patients, especially in those with a contact history, is important to prevent tuberculous infection in the general population. totally 26 patients, younger than 14 years of age, who had a diagnosis of pulmonary mycobacterium tuberculosis (tb), underwent both chest radiographs and computed tomography (ct), which were retrospectively reviewed and compared with those of 20 patients with community-acquired bacterial pneumonia (cabp). tb ...201122248827
immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (pids).natural human immunity to the mycobacteria group, including mycobacterium tuberculosis, bacille calmette-guérin (bcg) or nontuberculous mycobacteria (ntm), and/or salmonella species, relies on the functional il-12/23-ifn-γ integrity of macrophages (monocyte/dendritic cell) connecting to t lymphocyte/nk cells. patients with severe forms of primary immunodeficiency diseases (pids) have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies ...201122248828
cojedes: a leprosy hyperendemic state.background  leprosy is a chronic infectious disease produced by mycobacterium leprae. in 1997 venezuela reached the goal of elimination of leprosy as a public health problem (according to the world health organization a prevalence rate of ≤1/10,000 inhabitants), but five states still had prevalence rates over that goal. for this study we selected cojedes state, where prevalence rates remain over the elimination goal. objective  evaluate the real leprosy situation in high-prevalence areas of coje ...201222250629
an intramedullary tuberculous abscess of the conus in a 5-year-old child presenting with urinary dysfunction.to report a case of the primary presence of an intramedullary tuberculous abscess in the conus medullaris with neither a history of contact nor tuberculous infection elsewhere in the body.201122251511
sq109 targets mmpl3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of mycobacterium tuberculosis.sq109, a 1,2-diamine related to ethambutol, is currently in clinical trials for the treatment of tuberculosis, but its mode of action remains unclear. here we demonstrate that sq109 disrupts cell wall assembly as evidenced by macromolecular incorporation assays and ultrastructural analyses. sq109 interferes with the assembly of mycolic acids into the cell wall core of mycobacterium tuberculosis, as bacilli exposed to sq109 show immediate inhibition of trehalose dimycolate (tdm) production and fa ...201222252828
glycopeptidolipids: immuno-modulators in greasy mycobacterial cell envelope.species of opportunistic mycobacteria are the major causative agent for disseminating pulmonary infections in immuno-compromised individuals. these naturally resistant strains recruit a unique type of glycolipid known as glycopeptidolipids (gpls), noncovalently attached to the outer surface of their thick lipid rich cell envelope. species specific gpls constitute the chemical determinants of most nontuberculous mycobacterial serotypes, and their absence from the cell surface confers altered colo ...201222252955
autoluminescent mycobacterium tuberculosis for rapid, real-time, non-invasive assessment of drug and vaccine efficacy.preclinical efforts to discover and develop new drugs and vaccines for tuberculosis are hampered by the reliance on colony-forming unit (cfu) counts as primary outcomes for in vivo efficacy studies and the slow growth of mycobacterium tuberculosis. the utility of bioluminescent m. tuberculosis reporter strains for real-time in vitro and ex vivo assessment of drug and vaccine activity has been demonstrated but a simple, non-invasive, real-time surrogate marker to replace cfu counts for real-time ...201222253776
acanthamoeba polyphaga-enhanced growth of mycobacterium smegmatis.mycobacterium smegmatis is a rapidly-growing mycobacterium causing rare opportunistic infections in human patients. it is present in soil and water environments where free-living amoeba also reside, but data regarding m. smegmatis-amoeba relationships have been contradictory from mycobacteria destruction to mycobacteria survival.201222253795
sero-epidemiology as a tool to screen populations for exposure to mycobacterium ulcerans.previous analyses of sera from a limited number of ghanaian buruli ulcer (bu) patients, their household contacts, individuals living in bu non-endemic regions as well as european controls have indicated that antibody responses to the m. ulcerans 18 kda small heat shock protein (shsp) reflect exposure to this pathogen. here, we have investigated to what extent inhabitants of regions in ghana regarded as non-endemic for bu develop anti-18 kda shsp antibody titers.201222253937
coronin-1a inhibits autophagosome formation around mycobacterium tuberculosis-containing phagosomes and assists mycobacterial survival in macrophages.mycobacterium tuberculosis is an intracellular bacterium that can survive within macrophages. such survival is potentially associated with coronin-1a (coro1a). we investigated the mechanism by which coro1a promotes the survival of m. tuberculosis in macrophages and found that autophagy was involved in the inhibition of mycobacterial survival in coro1a knockdown (kd) macrophages. fluorescence microscopy and immunoblot analyses revealed that lc3, a representative autophagic protein, was recruited ...201222256790
spoligotyping of mycobacterium africanum, burkina faso.using ziehl-neelsen-positive slides collected from tuberculosis diagnostic centers in burkina faso, we showed that 20% of 80 spoligotyping-positive dna samples had a characteristic mycobacterium africanum-specific genomic signature. this result suggests that m. africanum is still present in burkina faso at almost the same prevalence as 15-20 years ago.201222257494
pyrazinamide susceptibility testing in all isolates of the mycobacterium tuberculosis complex - a critical analysis. 201222257727
performance assessment of a novel two-step mda-pcr (multiple displacement amplification as a pre-polymerase chain reaction) assay for detection of mycobacterium tuberculosis complex from sputum specimens.a novel two-step mda-pcr (multiple displacement amplification as a pre-polymerase chain reaction) assay for tuberculosis detection from 200 sputum specimens was evaluated. the mda-pcr assay indicated a significant increase in sensitivity and specificity compared with standard pcr alone.201222259205
effects of decontamination, dna extraction and amplification procedures on the molecular diagnosis of mycobacterium ulcerans disease (buruli ulcer).we compared two dna extraction methods (a semi-automated method using maxwell® kit and a modified boom method) and three amplification procedures (a single-step pcr, a nested pcr and a real-time quantitative pcr) on 74 surgical tissue specimens from clinically suspected buruli ulcer patients. all these procedures were compared before and after decontamination.we observed that, among the procedures tested, real-time pcr after the modified boom extraction method or a single-run pcr assay after the ...201222259213
[nontuberculous mycobacteria in wet areas of a hospital and standard residences].from 1998 to 2000, uoeh hospital identified a problem with bronchoscopes which were contaminated with mycobacteria. while conducting research into the problem, we found an extensive amount of nontuberculous mycobacteria (ntm) in wet areas. in this study, we collected a total of 114 samples to screen wet areas such as drains and taps in our hospital and in standard residences. we used the ziehl-neelsen staining method and specific pcr for mycobacteria. as a result, mycobacteria were detected in 9 ...201122259837
evaluation of capilia tb assay for rapid identification of mycobacterium tuberculosis complex in bactec mgit 960 and bactec 9120 blood cultures.abstract: background: capilia tb is a simple immunochromatographic assay based on the detection of mpb64 antigen specifically secreted by the mycobacterium tuberculosis complex (mtc). capilia tb was evaluated for rapid identification of mtc from bactec mgit 960 and bactec 9120 systems in kampala, uganda. since most studies have mainly dealt with respiratory samples, the performance of capilia tb on blood culture samples was also evaluated. methods: one thousand samples from pulmonary and dissem ...201222260090
mycobacterium tuberculosis infection of the placenta: a study of the early (innate) inflammatory response in two cases.abstract infections with mycobacterium tuberculosis (mtb) are widely disseminated in many countries, yet, descriptions of placental pathology in tuberculous patients are scanty. the usual necrotizing granulomatous response associated with tuberculous infections requires an activation of the adaptive immune system. however, before this system is turned on, the first encounter with the tubercle bacillus is mediated by the innate immune system. this pathway utilizes innate surface receptors in ...201222260536
mycobacterium riyadhense pulmonary infection, france and bahrain.to the editor: mycobacterium riyadhense is a newly described mycobacterial species that is potentially pathogenic for humans. extrapulmonary infection with this nontuberculous mycobacterium (ntm) has been reported (1).we report 2 cases of pulmonary infection with this ntm.201222261434
the pathology of mycobacterium tuberculosis infection.mycobacterium tuberculosis is an old enemy of the human race, with evidence of infection observed as early as 5000 years ago. although more host-restricted than mycobacterium bovis, which can infect all warm-blooded vertebrates, m. tuberculosis can infect, and cause morbidity and mortality in, several veterinary species as well. as m. tuberculosis is one of the earliest described bacterial pathogens, the literature describing this organism is vast and overwhelming. this review strives to distill ...201222262351
mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive cd4 t cells.mycobacterium tuberculosis promotes its replication by inhibiting the apoptosis of infected macrophages. a proapoptotic m. tuberculosis mutant lacking nuog, a subunit of the type i nadh dehydrogenase complex, exhibits attenuated growth in vivo, indicating that this virulence mechanism is essential. we show that m. tuberculosis also suppresses neutrophil apoptosis. compared to wild-type, the nuog mutant spread to a larger number of lung phagocytic cells. consistent with the shorter lifespan of in ...201222264515
synthesis and evaluation of anti-tubercular and antibacterial activities of new 4-(2,6-dichlorobenzyloxy)phenyl thiazole, oxazole and imidazole derivatives. part 2.a series of substituted 4-(2,6-dichlorobenzyloxy)phenyl thiazole, oxazole and imidazole derivatives were synthesized. the derivatives were screened for in vitro anti-tubercular activities against mycobacterium tuberculosis h37rv using the microplate alamar blue assay (maba), and antibacterial activities with agar dilution method against clinical s. aureus, e. coli, s. pneumoniae and penicilin-resistant s. pneumoniae. among 15 compounds, several thiazole derivatives exhibited good anti-tubercular ...201222264895
persistently bound ku at dna ends attenuates dna end resection and homologous recombination.dna double strand breaks (dsbs) are repaired by non-homologous end joining (nhej) or homologous recombination (hr). the dna cell cycle stage and resection of the dsb ends are two key mechanisms which are believed to push dsb repair to the hr pathway. here, we show that the nhej factor ku80 associates with dsbs in s phase, when hr is thought to be the preferred repair pathway, and its dynamics/kinetics at dsbs is similar to those observed for ku80 in non-s phase in mammalian cells. a ku homolog f ...201222265216
the mycobacterium avium esx-5 ppe protein, ppe25-mav, interacts with an esat-6 family protein, mav_2921, and localizes to the bacterial surface.previous research has demonstrated that inactivation of the mycobacterium avium gene, ppe25-mav (mav-2928), leads to a significant attenuation of virulence in both in vitro and in vivo models. ppe25-mav encodes for a ppe family protein, a family from which many members have been implicated in both bacterial virulence and host immune recognition. recent research has shown that many ppe family proteins are exported by a specialized type vii secretion system in mycobacteria. in this context, the me ...201222265661
in this issue.cover image: the cover is based on a spinal cord histology section taken from a tnfr2(-/-) mouse adoptively transferred with tnfr2(-/-) treg cells prior to immunization with mog(35-55) to induce eae. the section is stained with luxol fast blue to detect demyelination; luxol fast red, which detects inflammatory infiltration, is the counterstain. the image is taken from the article by tsakiri et al. (pp. 403-412) in which it is shown that tnfr2 on non-haematopoietic cells is necessary for treg- ...201222266713
risk of progression to active tuberculosis following reinfection with mycobacterium tuberculosis.background. the risk of progression to active tuberculosis is greatest in the several years following initial infection. the extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. indirect estimates from population models have been highly variable.methods. we reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of la ...201222267721
coa adducts of 4-oxo-4-phenylbut-2-enoates: inhibitors of menb from the m. tuberculosis menaquinone biosynthesis pathway.a high-throughput screen led to the discovery of 2-amino-4-oxo-4-phenylbutanoate inhibitors of the 1,4-dihydroxy-2-naphthoyl-coa synthase (menb) from the menaquinone biosynthesis pathway in mycobacterium tuberculosis. however, these compounds are unstable in solution and eliminate to form the corresponding 4-oxo-4-phenylbut-2-enoates that then react with coa in situ to form nanomolar inhibitors of menb. the potency of these compounds results from interaction of the coa adduct carboxylate with th ...201122267981
identification of the leprosy agent mycobacterium lepromatosis in singapore.background: a new leprosy-causing species, namely mycobacterium lepromatosis, was discovered recently to be the cause of diffuse lepromatous leprosy (dll) in mexico. it is unknown whether this organism exists beyond mexico. methods: we sought to determine the identity of the mycobacteria in the skin tissue of two patients from singapore who died of dll. dna was extracted from archived biopsy tissue, and conserved polymerase chain reaction primers were used to amplify and sequence two to three my ...201222270197
epidemiology of bloodstream infections and predictive factors of mortality among hiv-infected adult patients in thailand in the era of highly active antiretroviral therapy.few studies have described the pattern of bloodstream infections (bsi) among hiv-infected patients in the highly active antiretroviral therapy (haart) era, particularly in resource-limited settings. a retrospective cohort study was conducted among 140 hiv-infected patients who had a positive blood culture from 2004-2008. of the 140 patients, 91 (65%) were male with a mean (sd) age of 38 (9.1) years and a median (iqr) cd4 cell count of 32 (9-112) cells/mm(3). community-acquired infection was ...201222274154
snp genotypes of mycobacterium leprae isolates in thailand and their combination with rpot and ttc genotyping for analysis of leprosy distribution and transmission.based on the discovery of three single nucleotide polymorphisms (snps) in mycobacterium leprae, it has been previously reported that there are four major snp types associated with different geographic regions around the world. another typing system for global differentiation of m. leprae is the analysis of the variable number of short tandem repeats within the rpot gene. to expand the analysis of geographic distribution of m. leprae, classified by snp and rpot gene polymorphisms, we studied ...201222274158
label-free detection of a bacterial pathogen using an immobilized siderophore, deferoxamine.pathogenic bacteria obtain the iron necessary for survival by releasing an iron chelator, termed a siderophore, and retrieving the iron-siderophore complex via a cell surface siderophore receptor. we have exploited the high affinity of yersinia enterocolitica for its siderophore, deferoxamine, to develop a rapid method for capture and identification of yersinia. in this methodology, a deferoxamine-bovine serum albumin conjugate is printed onto a gold-plated chip in a parallel line pattern. after ...201222274807
a pseudokinase debut at the mycobacterial cell wall.mycobacterium tuberculosis, the causative agent of tuberculosis, has a complex cellular envelope that comprises both the cytoplasmic membrane and the outer cell wall. despite advances in elucidating the structural and biochemical composition of these features, the processes that ensure cell wall homeostasis remain poorly understood. new findings implicate the essential mycobacterial serine-threonine protein kinase (stpk), pknb, in regulating the formation of a regulatory complex that includes th ...201222275218
a phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (pg) biosynthesis in mycobacterium tuberculosis. we found that pknb, a pg-responsive ser-thr protein kinase (stpk), initiates complex assembly by phosphorylating a kinase-like domain in the essential pg biosynthetic protein, mvin. this domain was structurally ...201222275220
mycobacterial induction of autophagy varies by species and occurs independently of mtor inhibition.the interaction of host cells with mycobacteria is complex and can lead to multiple outcomes ranging from bacterial clearance to latent infection. while many factors are involved, the mammalian autophagy pathway is recognized as a determinant that can influence the course of infection. intervention aimed at utilizing autophagy to clear infection requires an examination of the autophagy and signal transduction induced by mycobacteria under native conditions. with both pathogenic and non-pathoge ...201222275355
inhibition of the plasma-membrane-associated serine protease cathepsin g by mycobacterium tuberculosis rv3364c suppresses caspase-1 and pyroptosis in macrophages.tuberculosis is a disease associated with the infection of a great part of the world's population and is responsible for the death of two to three million people annually. mycobacterium tuberculosis infects macrophages and subverts its mechanisms of killing. the pathogen suppresses macrophage apoptosis by many different mechanisms. we describe that, upon uptake by macrophages, m. tuberculosis overexpresses an operon rv3361c-rv3365c and secretes rv3364c. the rv3365c knockout strain is deficient i ...201222275911
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