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[Effects of Mycobacterium tuberculosis Hsp16.3 protein on the autophagy fun-ction of mice macrophages].To investisate the inhibition of Hsp-16.3 on the autophagosomes formation of macrophages.201122152810
Amide isosteres in structure-activity studies of antibacterial minor groove binders.Antibacterial minor groove binders related to the natural product, distamycin, are development candidates for novel antibiotics. Alkenes have been found to be effective substitutes for the isosteric amide links in some positions and alkyl groups larger than methyl have been found to increase binding to DNA in both selectivity and affinity. However the impact of other isosteres such as diazenes and the position of an alkyl group with respect to DNA binding and antibacterial activity are not known ...201121908079
Rapid Identification of Mycobacteria and Drug Resistant Mycobacterium tuberculosis using a Single Multiplex PCR and DNA Sequencing.Tuberculosis (TB) remains a significant global health problem for which rapid diagnosis is critical to both treatment and control. This report describes a multiplex PCR method, the Mycobacterial IDentification and Drug Resistance Screen (MID-DRS) assay, which allows for identification of Mycobacterium tuberculosis Complex (MTBC) and the simultaneous amplification of targets for sequencing-based drug resistance ((R)) screening of rifampin, isoniazid and pyrazinamide. Additionally, the same multip ...201122162548
Specificity of a whole blood IGRA in German nursing students.Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated.201121929799
Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV-1 infected individuals in vivo.The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified pr ...201122087280
Risk factors for Mycobacterium tuberculosis infection among children in Greenland.To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection.201122084512
Evaluation of a simple loop-mediated isothermal amplification test kit for the diagnosis of tuberculosis.A new loop-mediated isothermal amplification (LAMP) test kit, including a simple DNA extraction device for the detection of Mycobacterium tuberculosis complex, was developed for commercial use and evaluated for its usefulness in diagnosing tuberculosis (TB).201121943848
Synthesis and biological evaluation of some novel 1,4-dihydropyridines as potential antitubercular agents.Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. In this study, we have synthesized new derivatives of 1,4-dihydropyridines bearing carbmethoxy and carbethoxy group at C-3 and C-5 of the 1,4-dihydropyridine ring. In addition, 1H-pyrazole ring is substituted at C-4 position. These analogues were synthesized by multi-component Hantzsch reaction. The in vitro antitubercular activity of compounds against Mycob ...201121895982
novel mycobacterium species in seahorses with tail rot. 201121888823
Phenylethyl-butyrate enhances the potency of second-line drugs against clinical isolates of M. tuberculosis.Ethionamide (ETH) is a second line drug for the treatment of tuberculosis. As a pro-drug, ETH has to be activated by EthA. ethA is controlled by its repressor EthR. 2-phenylethyl-butyrate (2-PEB) inhibits EthR-binding, enhances expression of EthA and thereby enhances the growth inhibitory effects of ethionamide, isoxyl and thiacetazone in M. tuberculosis strains with resistance to ETH due to inhA-promoter mutations but not ethA-mutations.201122106218
Evidence for oxidative stress and defective antioxidant response in guinea pigs with tuberculosis.The development of granulomatous inflammation with caseous necrosis is an important but poorly understood manifestation of tuberculosis in humans and some animal models. In this study we measured the byproducts of oxidative stress in granulomatous lesions as well as the systemic antioxidant capacity of BCG vaccinated and non-vaccinated guinea pigs experimentally infected with Mycobacterium tuberculosis. In non-vaccinated guinea pigs, oxidative stress was evident within 2 weeks of infection as me ...201122028843
Comparative transcriptional study of the putative mannose donor biosynthesis genes in virulent Mycobacterium tuberculosis and attenuated Mycobacterium bovis BCG strains.Mycobacterium tuberculosis contains mannosylated cell wall components which are important in macrophage recognition and response. The building block for the mannosyl constituents of these components is GDP-mannose, which is synthesized through a series of enzymes involved in the mannose donor biosynthesis pathway. Nothing is known about the expression levels of the genes encoding these enzymes during the course of infection. To generate transcriptional profiles for the mannose donor biosynthesis ...201121896775
[Non-tuberculous mycobacterial infection in patients with non-cystic fibrosis bronchiectasias.]AIMS: To know the characteristics and prevalence of non-tuberculous mycobacterial infection infection in patients with non-cystic fibrosis bronchiectasis. PATIENTS AND METHODS: A retrospective descriptive study of NCFB adult patients whose disease had been followed-up for at least two years was performed. RESULTS: A total of 68 subjects were included, 50 females (73.5%), with mean age of 63.31± 16.2 years. The most frequent etiology of the non-cystic fibrosis bronchiectasis was COPD in 28 cases ...201122119262
Autophagy as an innate immunity paradigm: expanding the scope and repertoire of pattern recognition receptors.Autophagy is rapidly developing into a new immunological paradigm. The latest links now include overlaps between autophagy and innate immune signaling via TBK-1 and IKKa/ß, and the role of autophagy in inflammation directed by the inflammasome. Autophagy's innate immunity connections include responses to pathogen and damage-associated molecular patterns including alarmins such as HMGB1 and IL-1ß, Toll-like receptors, Nod-like receptors including NLRC4, NLRP3 and NLRP4, and RIG-I-like receptors. ...201122118953
Can Tissue PCR Augment the Diagnostic Accuracy in Genitourinary Tract Tuberculosis?Purpose: Conventional methods like smear and culture for Mycobacterium tuberculosis are of limited sensitivity and specificity. Histopathological examination (HPE) for the tissues obtained gives inconclusive diagnosis in the absence of caseous necrosis or stained acid-fast bacilli. This study was conducted to determine the utility of tissue PCR for diagnosing tuberculosis of the genitourinary tract (GUTB) and its comparative evaluation with HPE. Patients and Methods: A prospective study was cond ...201122134187
prospective on mycobacterium tuberculosis proteomics.mycobacterium tuberculosis, the causative agent of tuberculosis, remains one of the most prevalent human pathogens in the world. knowledge regarding the bacilli's physiology as well as its mechanisms of virulence, immunogenicity, and pathogenesis has increased greatly in the last three decades. however, the function of about one-quarter of the mtb coding genome and the precise activity and protein networks of most of the mtb proteins are still unknown. protein mass spectrometry and a new interes ...201121988637
[effects of mycobacterium phlei f.u.36 on regulatory t cells and tlr4 expression in asthmatic mice].to study the effects of early intervention on cd4+cd25+ regulatory t cells and tlr4 expression with mycobacterium phlei f.u.36 in asthmatic mice.201122099205
[histopathological examination of buruli ulcer (mycobacterium ulcerans disease) in surgically removed skin].we report the results of an examination of gross images of two patients with buruli ulcer and a histopathological evaluation of surgically removed skin from two other cases at the non-ulcerated and ulcerated stages, respectively. histopathologically, dermal nodes were found in the non-ulcerated specimen; while wide necrosis of skin and fibrin deposition, as well as langhans giant cell, epitheloid cells, and vasculitis, were observed in the ulcerated specimen, with granuloma in the lymph nodes. m ...201121941833
antimicrobial activity of new phorbins from jatropha curcas linn. (euphorbiaceae) leaves.the crude methanol extract of jatropha curcas leaves exhibited activity against staphylococcus aureus, bacillus subtilis, mycobacterium phlei, candida albicans, and trichophyton mentagrophytes but was inactive against escherichia coli, pseudomonas aeruginosa, and saccharomyces cerevisiae. in a bioassay-directed fractionation, two new phorbins were isolated and analysed by spectroscopic methods. isolate 1 was characterized as an analogue of pheophytin b with a phytyl moiety containing three doubl ...201122191207
characterization of clioquinol and analogues as novel inhibitors of methionine aminopeptidases from mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis claims about five thousand lives daily world-wide, while one-third of the world is infected with dormant tuberculosis. the increased emergence of multi- and extensively drug-resistant strains of m. tuberculosis (mtb) has heightened the need for novel antimycobacterial agents. here, we report the discovery of 7-bromo-5-chloroquinolin-8-ol (clbq14)-a congener of clioquinol (cq) as a potent and selective inhibitor of two methionine ami ...201122115541
Course of murine tuberculosis and response to first-line therapy depends on route of infection and inoculum size.In the search for new anti-tuberculosis drugs, numerous potential drugs are being screened in vitro. In animal models, promising new anti-tuberculosis drugs are assessed in terms of toxic side effects and comparative therapeutic efficacy. Mice are frequently used and experimental infections are established in different ways.201122008760
molecular, kinetic and thermodynamic characterization of mycobacterium tuberculosis orotate phosphoribosyltransferase.tuberculosis (tb) is a chronic infectious disease caused mainly by mycobacterium tuberculosis. the worldwide emergence of drug-resistant strains, the increasing number of infected patients among immune compromised populations, and the large number of latent infected individuals that are reservoir to the disease have underscored the urgent need of new strategies to treat tb. the nucleotide metabolism pathways provide promising molecular targets for the development of novel drugs against active tb ...201122075667
CD8a(+) and CD8a(-) DC subsets from BCG-infected mice inhibit allergic Th2-cell responses by enhancing Th1-cell and Treg-cell activity respectively.The hygiene hypothesis has suggested an inhibitory effect of infections on allergic diseases, but the related mechanism remains unclear. We recently reported that DCs played a critical role in Mycobacterium bovis Bacille Calmette-Guérin (BCG)-mediated inhibition of allergy, which depended on IL-12 and IL-10-related mechanisms. Here, we tested the hypothesis that BCG infection could modulate the function of DC subsets, which might in turn inhibit allergic responses through different mechanisms. W ...201122009696
antibacterial and antitubercular activity of fosmidomycin, fr900098, and their lipophilic analogs.the nonmevalonate pathway (nmp) of isoprene biosynthesis is an exciting new route toward novel antibiotic development. inhibitors against several enzymes in this pathway are currently under examination. a significant liability of many of these agents is poor cell penetration. to overcome and improve our understanding of this problem, we have synthesized a series of lipophilic, prodrug analogs of fosmidomycin and fr900098, inhibitors of the nmp enzyme dxr. several of these compounds show improved ...201122024034
Automated quantitative drug susceptibility testing of non-tuberculous mycobacteria using MGIT 960/EpiCenter TB eXiST.Objectives To assess the predictive value of in vitro drug susceptibility testing (DST) in slow-growing non-tuberculous mycobacteria (NTM), knowledge on quantitative levels of drug susceptibility should be available. The aim of this study was to investigate the suitability of the MGIT 960/TB eXiST system for quantitative DST of NTM. Methods We have assessed quantitative levels of drug susceptibility for clinical isolates of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium kan ...201221965431
Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?Until 2004, the skin disease known as Buruli ulcer, caused by Mycobacterium ulcerans, could only be treated by surgery and skin grafting. Although this worked reasonably well on early lesions typically found in patients in Australia, the strategy was usually impractical on large lesions resulting from diagnostic delay in patients in rural West Africa. Based on promising preclinical studies, treatment trials in West Africa have shown that a combination of rifampin and streptomycin administered da ...201122004037
Total synthesis of polyprenyl N-glycolyl lipid II as a mycobacterial transglycosylase substrate.A feasible synthetic approach toward the Mycobacterium tuberculosis (Mtb) N-glycolyl lipid II-like molecule 1 is described. Compound 1 bears pendant undecaprenol and l-lysin moieties instead of the naturally occurring decaprenol and meso-diaminopimelic acid, which are not readily available. Functionalization of 1 with a fluorophore on the peptide side chain gave 14, which was found to be recognized as an Mtb TGase substrate. This result suggests it has tremendous utility for mechanistic studies, ...201121913698
localised mycobacterium ulcerans infection in four dogs.localised infection caused by mycobacterium ulcerans is described in two kelpies, a whippet and a koolie domiciled on the bellarine peninsula, victoria, australia. the diagnosis was confirmed using real-time polymerase chain reaction (pcr) targeting the m. ulcerans-specific insertion sequence (is2404) in dna extracted from swabs of ulcerated lesions in all cases. where available, molecular typing confirmed that three of the dogs were infected with a strain of m. ulcerans that was indistinguishab ...201122103951
a universal multiplex pcr strategy for 100-plex amplification using a hydrophobically patterned microarray.both basic research and clinical medicine have urgent demands for highly efficient strategies to simultaneously identify many different dna sequences within a single tube. effective and simultaneous amplification of multiple target sequences is a prerequisite for any successful multiple nucleic acid detection method. multiplex pcr is one of the best choices for this purpose. however, due to the intrinsic interference and competition among primer pairs in the same tube, multiple rounds of highly ...201121909519
the potential role of garlic (allium sativum) against the multi-drug resistant tuberculosis pandemic: a review.worldly data show the increasing incidence of mycobacterium tuberculosis (mtb) and particularly of multi-drug resistant tuberculosis (mdr-tb). in developing countries, tb control programmes are overwhelmed by the complexity of treating mdr-tb infected people, as current tools and therapies are inadequate. mdr-tb could become the main form of tb. risk factors that make south africa into one of the main epicentres are analysed. a review of the studies carried out about antitubercular properties of ...201122194081
the role of abc efflux pump, rv1456c-rv1457c-rv1458c, from mycobacterium tuberculosis clinical isolates in china.recently the atp-binding cassette (abc) efflux pumps have been proved to be a major component of drug resistance in mycobacterium tuberculosis. the objective of this study was to investigate the expression profiles of rv1456c-rv1457c-rv1458c efflux system in clinical isolates of m. tuberculosis and its involvement in drug-resistance mechanisms. significantly increased mrna expression of rv1456c, rv1457c, and rv1458c appeared among the clinical isolates (p < 0.05), which are resistant to at least ...201122083788
examining the role of rv2895c (viub) in iron acquisition in mycobacterium tuberculosis.iron acquisition is essential for mycobacterium tuberculosis (mtb) virulence. understanding the molecular mechanisms used by mtb to scavenge iron during infection might reveal new targets for antimicrobial development. rv2895c, a homolog of viub from vibrio cholerae has been postulated to be involved in iron-siderophore uptake and utilization in mtb. this study examines the requirement of rv2895c for adaptation of mtb to iron limitation. we show that rv2895c is dispensable for normal replication ...201122015175
does clofazimine prevent erythema nodosum leprosum (enl) in leprosy? a retrospective study, comparing the experience of multibacillary patients receiving either 12 or 24 months who-mdt.to compare the occurrence, duration and severity of enl in leprosy patients treated with either 12 or 24 months of standard multi-drug therapy (mdt).201122125929
Epidemiological analysis of Mycobacterium tuberculosis strains isolated in Lodz, Poland.Mycobacterium tuberculosis is one of the most dangerous human pathogens. Molecular typing of M. tuberculosis has allowed better control of tuberculosis and, among other benefits, identification of genetic lineages among strains.201121943854
A study of knowledge, attitude and practices regarding leprosy among undergraduates and interns of a medical college and hospital from rural India.Leprosy is an Infectious disease caused by Mycobacterium leprae and acquired through droplet infection. India has been carrying the 2/3rd global leprosy burden. Inadequate or incorrect information and knowledge about the disease and its treatment are the root causes of many stigmas and inhibitions prevalent in the various sections of the community. The present study was undertaken to assess the knowledge, attitude and practices (KAP) regarding leprosy among undergraduates (final year medical stu ...201121972659
A mathematical model for cellular immunology of tuberculosis.Tuberculosis (TB) is a global emergency. The World Health Organization reports about 9.2 million new infections each year, with an average of 1.7 million people killed by the disease. The causative agent is Mycobacterium tuberculosis (Mtb), whose main target are the macrophages, important immune system cells. Macrophages and T cell populations are the main responsible for fighting the pathogen. A better understanding of the interaction between Mtb, macrophages and T cells will contribute to the ...201121936595
Pigs as an experimental model for systemic Mycobacterium avium infectious disease.Mycobacterium avium complex (MAC) is an opportunistic pathogen in AIDS patients and pigs, and causes dissemination through primary intestinal lesions. However, its pathogenesis is not well understood. In this article, we hypothesize that pigs can provide a suitable experimental model of disseminated MAC disease. We compared the initial route of infection, the characteristics of the pathogenic strains, the immunological status of the hosts, and the histological characteristics. The route of infec ...201121992722
Assembly and proteolytic processing of mycobacterial ClpP1 and ClpP2.ABSTRACT: BACKGROUND: Caseinolytic proteases (ClpPs) are barrel-shaped self-compartmentalized peptidases involved in eliminating damaged or short-lived regulatory proteins. The Mycobacterium tuberculosis (MTB) genome contains two genes coding for putative ClpPs, ClpP1 and ClpP2 respectively, that are likely to play a role in the virulence of the bacterium. RESULTS: We report the first biochemical characterization of ClpP1 and ClpP2 peptidases from MTB. Both proteins were produced and purifi ...201122132756
Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis o ...201122102165
consensus statement on diagnostic end points for infant tuberculosis vaccine trials.background. definition of clinical trial end points for childhood tuberculosis is hindered by lack of a standard case definition. we aimed to identify areas of consensus or debate on potential end points for tuberculosis vaccine trials among human immunodeficiency virus-uninfected children.methods. thirty-eight opinion leaders participated in a consensus workshop at the second global forum on tb vaccines (estonia, 2010). outcomes were categorized as unanimity, modified consensus, or lack of cons ...201122144538
[Nontuberculous mycobacteria: M. marinum, M. ulcerans, M. xenopi - brief characteristics of the bacteria and diseases caused by them].Mycobacterium is a variable group of acid-fast bacillus which contains pathogenic bacteria causing tuberculosis (MTC - Mycobacterium tuberculosis complex) and leprosy (M. leprae) as well as numerous nontuberculous mycobacteria (NTM) causing diseases mostly in people with immunodeficiency, although some NTM strains are capable of causing illnesses in non-immunocompromised patients. This group includes for example Mycobacterium marinum, Mycobacterium ulcerans and Mycobacterium xenopi. These microo ...201121918261
The role of neuregulin-1 in the response to nerve injury.Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors ...201122121335
Characterization of an oxidoreductase from the arylamine N-acetyltransferase operon in Mycobacterium smegmatis.Mycobacterium tuberculosis, the most successful bacterial pathogen, causes tuberculosis, a disease that still causes more than 2 million deaths per year. Arylamine N-acetyltransferase is an enzyme that is conserved in most Mycobacterium spp. The nat gene belongs to an operon that is important for the intracellular survival of M. tuberculosis within macrophages. The nat operon in Mycobacterium smegmatis and other fast-growing mycobacterial species has a unique organization containing genes with u ...201121972977
Impact of Fgd1 and ddn diversity in Mycobacterium tuberculosis complex on in vitro susceptibility to PA-824.PA-824 is a promising drug candidate for the treatment of tuberculosis (TB). It is in phase II clinical trials as part of the first newly designed regimen containing multiple novel antituberculosis drugs (PA-824 in combination with moxifloxacin and pyrazinamide). However, given that the genes involved in resistance against PA-824 are not fully conserved in the Mycobacterium tuberculosis complex (MTBC), this regimen might not be equally effective against different MTBC genotypes. To investigate t ...201121930879
Inverted repeats in the promoter as an autoregulatory sequence for TcrX in Mycobacterium tuberculosis.TcrY, a histidine kinase, and TcrX, a response regulator, constitute a two-component system in Mycobacterium tuberculosis. tcrX, which is expressed during iron scarcity, is instrumental in the survival of iron-dependent M. tuberculosis. However, the regulator of tcrX/Y has not been fully characterized. Crosslinking studies of TcrX reveal that it can form oligomers in vitro. Electrophoretic mobility shift assays (EMSAs) show that TcrX recognizes two regions in the promoter that are comprised of i ...201122001925
toxin-antitoxin systems of mycobacterium smegmatis are essential for cell survival.the role of chromosomal toxin-antitoxin (ta) modules in bacterial physiology remain enigmatic despite their abundance in the genomes of many bacteria. mycobacterium smegmatis contains three putative toxin-antitoxin (ta) systems, vapbc, mazef and phd/doc, and previous work from our group has shown vapbc to be a bona fide ta system. in this communication we show that mazef and phd/doc are also ta systems that are constitutively expressed, transcribed as leaderless transcripts, subject to autoregul ...201122199354
disease transmission from companion parrots to dogs and cats: what is the real risk?a number of common misconceptions exist regarding the degree of transmission from companion parrots to dogs and cats. concern regarding bacterial, viral, fungal, and parasitic transmission is generally unfounded, because disease transmission between companion parrots and dogs and cats is not well-documented. infections with mycobacterium spp, aspergillus spp, giardia spp, chlamydophila psittaci, salmonella spp, yersinia pseudotuberculosis, cryptococcus neoformans, histoplasma capsulatum, cryptos ...201122041215
Genes under positive selection in Mycobacterium tuberculosis.We employed an evolutionary genomics approach to detect genes under lineage-specific positive selection for the two closely related Mycobacterium tuberculosis strains, the virulent H37Rv and the avirulent H37Ra, with the clinical isolate CDC1551 as the outgroup. We found six H37Rv-specific and six H37Ra-specific positively selected genes, among which the former comprised a flavoprotein, a RNA polymerase sigma factor SigM, two PPE family proteins, as well as two hypothetical proteins, while the l ...201122000803
Interferon-? release assays for the diagnosis of latent Mycobacterium tuberculosis infection. 201122045795
shorter-term risk of mycobacterium bovis in irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test.in ireland, new cases of bovine tuberculosis (btb) are detected using both field and abattoir surveillance (more and good, 2006). field surveillance is conducted through annual testing of all cattle using the single intradermal comparative tuberculin test (sictt). an animal may be deemed a 'standard inconclusive reactor' (sir) to the sictt if the bovine response is >2mm and between 1 and 4mm>the avian response. the herdowner then has three choices for the management of the sir: option 1 is to ha ...201121855153
Identification and Characterization of a Mycobacterial (2R,3R)-2,3-Butanediol Dehydrogenase.Bacterial strain B-009, capable of using racemic 1,2-propanediol (PD), was identified as a rapid-growing member of the genus Mycobacterium. The strain is phylogenetically related to M. gilvum, but has slightly different physiological characteristics. An NAD(+)-dependent enantioselective alcohol dehydrogenase, which acts on R-PD, was purified from the strain. The enzyme was a homodimer of a peptide coded by a 1047-bp gene (mbd1). A highly conserved sequence for medium-chain dehydrogenase/reductas ...201122146728
Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids.The mechanisms permitting nonpolymorphic CD1 molecules to present lipid antigens that differ considerably in polar head and aliphatic tails remain elusive. It is also unclear why hydrophobic motifs in the aliphatic tails of some antigens, which presumably embed inside CD1 pockets, contribute to determinants for T-cell recognition. The 1.9-Å crystal structure of an active complex of CD1b and a mycobacterial diacylsulfoglycolipid presented here provides some clues. Upon antigen binding, endogenous ...201122006319
Canadian Multicenter Laboratory Study for Standardized Second-Line Antimicrobial Susceptibility Testing of Mycobacterium tuberculosis.The purpose of this study was to establish a standardized protocol for second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis using the Bactec MGIT 960 system in Canadian laboratories. Four Canadian public health laboratories compared the susceptibility testing results of 9 second-line antimicrobials between the Bactec 460 and Bactec MGIT 960 systems. Based on the data generated, we have established that the Bactec MGIT 960 system provides results comparable to those obta ...201121998413
Gastrointestinal infection as a trigger for inflammatory bowel disease.There is accumulating evidence on the importance of microbes in the development and maintenance of both the intestinal and immune systems. This review focuses on the current findings on the role of gastrointestinal pathogens in the cause of chronic inflammatory bowel disease.201222080823
phenothiazines as anti-tubercular agents: mechanistic insights and clinical implications.introduction: tuberculosis (tb) chemotherapy has been rendered ineffective by the emergence of multi-drug resistant (mdr), extensively drug resistant (xdr) and totally drug resistant strains reinforcing the need for the development of new drugs as a global health priority. reconsidering phenothiazines for the improvement of tb chemotherapy seems to be a rational option especially in view of their role as inhibitors of type ii nadh dehydrogenase, a key component of respiratory chain of mycobacter ...201122014039
thalidomide induces mucosal healing in crohn's disease: case report.crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defined by relapsing and remitting episodes. tumor necrosis factor alpha (tnf-α) appears to play a central role in the pathophysiology of the disease. standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. biological therapies have been associated with an increased incidence of infections, especially infection by mycobacterium tuberculosis (mtb). thalidomide is a ...201122174554
diagnostic approach of childhood pulmonary tuberculosis in endemic areas of southeast nigeria.there is the need to ascertain the diagnostic approach on which medical doctors based their diagnosis of childhood pulmonary tuberculosis especially in tuberculosis endemic areas.201121970212
Report of three new leprosy cases in children under fifteen in the municipality of Itaguai, Rio de Janeiro: event alert for epidemiological investigation.Leprosy is an infectious disease with an average incubation period of two to five years. It is caused by Mycobacterium leprae, mainly affecting skin, mucous membranes and peripheral nerves. When it occurs in children under fifteen, it reflects an intense and long contact period, with a high bacillary load. Therefore, it is considered an important alert sign that points to the challenge of controlling the disease. The authors report three cases of leprosy in children under fifteen that occurred i ...201122147046
Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties.New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and 13a were active at 0.65 µg/mL against Mycobacterium tuberculosis H(37)Rv strain. The mode of action of these ...201121880400
Guanine nucleotides differentially modulate backbone dynamics of the STAS domain of the SulP/SLC26 transport protein Rv1739c of Mycobacterium tuberculosis.Enzymatic catalysis and protein signaling are dynamic processes that involve local and/or global conformational changes occurring across a broad range of time scales. (1) H-(15) N relaxation NMR provides a comprehensive understanding of protein backbone dynamics both in the apo (unliganded) and ligand-bound conformations, enabling both fast and slow internal motions of individual amino acid residues to be observed. We recently reported the structure and nucleotide binding properties of the sulfa ...201122118659
A history of leprosy in Iran during the 19th and 20th centuries.From ancient time leprosy has been regarded as a terrifying, stigmatized disease; nevertheless, its cause remained unidentified up to the late 19th century. For centuries numerous leprosy victims worldwide suffered from its morbidity and were socially isolated. The afflicted individuals were segregated because they were considered 'unclean' and had to live in leper colonies, generally under very poor conditions. Physicians believed that leprosy was an incurable, highly contagious, and hereditary ...201122039850
Tumor biomarker glycoproteins in the seminal plasma of healthy human males are endogenous ligands for DC-SIGN.DC-SIGN is an immune C-type lectin that is expressed on both immature and mature dendritic cells associated with peripheral and lymphoid tissues in humans. It is a pattern recognition receptor that binds to several pathogens including HIV-1, Ebola virus, Mycobacterium tuberculosis, Candida albicans, Helicobacter pylori, and Schistosoma mansoni. Evidence is now mounting that DC-SIGN also recognizes endogenous glycoproteins, and that such interactions play a major role in maintaining immune homeo ...201121986992
Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes.Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA po ...201122179134
[Tuberculosis: steady dynamics between past and present to imagine the future].Progress in understanding the biological processes that allow Mycobacterium tuberculosis to be a successful parasite have accelerated in the last twenty years. This progress has been stimulated by the return of tuberculosis (TB) as an important disease in industrialized countries, by its increase in emergent nations in the tail of population increases and poverty and by the spread of multiple drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis as a result of treatment failu ...201122051818
A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice.Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD)-fed New Zealand white rabbits immunized with mHSP65(91-105) compared with PBS-immunized or BSA-immuniz ...201122038107
association of mannose-binding lectin gene polymorphism with tuberculosis susceptibility and sputum conversion time.mannose-binding lectin (mbl) plays an important role in innate immunity. the effect of low mbl levels producing variants of mbl2 gene on tuberculosis (tb) has been controversial with some studies reporting it to confer protection against the disease, whereas others estimating a susceptibility relation. other than conducting a case-control study to evaluate the role of mbl a/b polymorphism on tb, we conducted a longitudinal study to check whether this mbl variant can influence the host response t ...201122050925
MmpL3 Is the Cellular Target of the Antitubercular Pyrrole Derivative BM212.The 1,5-diarylpyrrole derivative BM212 was previously shown to be active against multidrug-resistant clinical isolates and Mycobacterium tuberculosis residing within macrophages as well as against Mycobacterium avium and other atypical mycobacteria. To determine its mechanism of action, we identified the cellular target. Spontaneous Mycobacterium smegmatis, Mycobacterium bovis BCG, and M. tuberculosis H37Rv mutants that were resistant to BM212 were isolated. By the screening of genomic libraries ...201222024828
current diagnosis and management of peripheral tuberculous lymphadenitis.peripheral tuberculous lymphadenitis accounts for ~10% of tuberculosis cases in the united states. epidemiologic characteristics include a 1.4:1 female-to-male ratio, a peak age range of 30-40 years, and dominant foreign birth, especially east asian. patients present with a 1-2 month history of painless swelling of a single group of cervical lymph nodes. definitive diagnosis is by culture or nucleic amplification of mycobacterium tuberculosis; demonstration of acid fast bacilli and granulomatous ...201121865192
Disseminated Mycobacterium marinum infection in a hematopoietic stem cell transplant recipient.Mycobacterium marinum is a photochromogenic mycobacterium that is ubiquitous in the aquatic environment. In the general population, exposure to aquaria is the most common cause of M. marinum infection. Known as "swimmer's granuloma" or "fish tank granuloma," M. marinum is an occupational hazard for aquarium cleaners and fishermen. There are several reports in the literature of M. marinum infection in immunocompromised hosts, including those with solid organ transplants, but none in patients who ...201122093773
The galvanizing of Mycobacterium tuberculosis: an antimicrobial mechanism.Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues (Botella et al., 2011) describe a novel antimicrobial mechanism based on elevated levels of intraphagosomal Zn(2+) and the corresponding induction of bacterial genes to ameliorate this host-derived stress.201121925106
Mycobacterial infections in adult patients with hematological malignancy.We retrospectively analyzed the clinical and microbiological characteristics of adult patients with hematological malignancy and nontuberculous mycobacteria (NTM) infections from 2001 to 2010. During the study period, 50 patients with hematological malignancy and tuberculosis (TB) were also evaluated. Among 2,846 patients with hematological malignancy, 34 (1.2%) patients had NTM infections. Mycobacterium avium-intracellulare complex (13 patients, 38%) was the most commonly isolated species, foll ...201121901631
[Diagnosis and treatment of atypical mycobacterial infections of the respiratory tract].INTRODUCTION: Non tuberculous mycobacteria (NTM), unlike tuberculous mycobacteria, are not strictly human pathogens. The diagnosis of infection and the choice of treatment remain difficult. BACKGROUND: Evidence of a NTM in a pulmonary sample is not synonymous with infection. The diagnosis depends on the association of clinical, radiological and microbiological factors. If a NTM is isolated from a respiratory sample, the probability of infection depends on the species. The main NTMs responsible f ...201122152937
Antimycobacterial natural products - an opportunity for the Colombian biodiversity.It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and aver ...201122173186
"pseudo-beijing": evidence for convergent evolution in the direct repeat region of mycobacterium tuberculosis.mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. one particular m. tuberculosis genotype known as "beijing" has repeatedly been associated with drug resistance and has been emerging in some parts of the world. "beijing" strains are traditionally defined based on a characteristic spoligotyping pattern. we used three alternative genotyping techniques to revisit the phylogenet ...201121935448
lanostane and hopane triterpenes from the entomopathogenic fungus hypocrella sp. bcc 14524.seven new lanostane-type triterpenes, hypocrellols a-g (1-7), and six new hopane-type triterpenes, 7β,15α-dihydroxy-22(29)-hopene (8), 3β,7β-dihydroxy-22(29)-hopene (9), 3β-acetoxy-15α-hydroxy-22(29)-hopene (10), 3β,7β,15α,22-tetrahydroxyhopane (11), 3β-acetoxy-7β,15α,22-trihydroxyhopane (12), and 7β,15α,22-trihydroxyhopane (13), were isolated from the scale insect pathogenic fungus hypocrella sp. bcc 14524. the structures of the new compounds were elucidated by analyses of the nmr spectroscopic ...201121995505
improved long-term protection against mycobacterium tuberculosis beijing/w in mice after intra-dermal inoculation of recombinant bcg expressing latency associated antigens.bacille calmette-guérin (bcg) is the vaccine against tuberculosis (tb), but has varied efficacy in different geographical locations. recombinant strategies to genetically modify the organism to enhance the quality of the immune response have aimed at improving bcg efficacy. here we describe such a strategy using rbcgδurec∷hly expressing defined latency-associated antigens and test this construct for long-term protection against an isolate of the mycobacterium tuberculosis (mtb) beijing/w lineage ...201121871515
Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users.Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstr ...201121931790
mycobacterium smegmatis roxy is a repressor of oxys and contributes to resistance to oxidative stress and bactericidal ubiquitin-derived peptides.the mycobactericidal properties of macrophages include the generation of reactive oxygen intermediates and the delivery of bacteria to a hydrolytic lysosome enriched in bactericidal ubiquitin-derived peptides (ub-peptides). to better understand the interactions of ubiquitin-derived peptides with mycobacteria and identify putative mycobacterial intrinsic resistance mechanisms, we screened for transposon mutants with increased susceptibility to the bactericidal ub-peptide ub2. we isolated 27 mycob ...201121984791
the long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. current options for leprosy prevention are contact tracing and bcg vaccination of infants. future options may include chemoprophylaxis and early diagnosis of subclinical infections. this study compared the predicted trends in leprosy case detection of future intervention strategies.201121949895
paratuberculosis vaccination.one vaccine, mycopar, is licensed for use in us cattle. the vaccine reduces clinical disease and fecal shedding of mycobacterium avium subsp. paratuberculosis (map). the vaccine is indicated for use in herds with a high map infection prevalence or herds with limited resources for implementing paratuberculosis control measures. in heavily infected herds, a combination of vaccination and disease control measures can help protect susceptible young stock while reducing environmental burdens and limi ...201122023835
molecular profile of drug resistance in tuberculous meningitis from southwest china.tuberculous meningitis (tbm) is the most severe form of extrapulmonary tuberculosis and causes high mortality and morbidity. isoniazid resistance is strongly predictive of death in patients with tbm.201122021920
unexpected high responses to tuberculin skin-test in farmed red deer: implications for tuberculosis control.tuberculosis (tb) in deer is a serious zoonotic disease of worldwide distribution. detection of infected animals is usually performed using single or comparative skin-testing (sst/cst), although false responses due to sensitization to other mycobacteria may occur, hampering diagnostic specificity. we describe the evolution of the responses to the sst, cst and to an in-house serological assay in a red deer farm subjected to regular tb testing in southern spain in an attempt to understand the dyna ...201122197268
[Establishment of RAW264.7 cell line stably expressing Mycobacterium tuberculosis protein ESAT-6].For studying the effects of Mycobacterium tuberculosis secretory protein ESAT-6 on the related functions of macrophages, RAW264.7 cells were transfected with pEGFP-C1-ESAT-6 and pEGFP-C1 by liposome respectively. After screening with a high level of G418, the macrophage cell lines that stably expressed EGFP-ESAT-6 fusion protein or EGFP were established. The gene and protein expression levels were further analyzed by RT-PCR, fluorescence microscopy and Western blotting. The results indicated tha ...201122117523
Lupus Vulgaris Caused by Mycobacterium bovis. 201122056255
Clofazimine in the treatment of multidrug-resistant tuberculosis.Clin Microbiol Infect ABSTRACT: Clofazimine has shown activity against Mycobacterium tuberculosis, including multidrug-resistant strains in vitro and in animal studies. However, clinical experience with clofazimine in multidrug-resistant tuberculosis (MDR-TB) is scarce. We reported our clinical experience with 39 MDR-TB patients treated with combination regimens that included clofazimine. From January 2008 to March 2011, 39 patients received clofazimine for the treatment of MDR-TB in Shanghai Pu ...201122192631
Plasma antibody profiles as diagnostic biomarkers for tuberculosis.Two billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), worldwide. Ten million to 20 million of the infected individuals develop disease per year. TB is a treatable disease, provided that it is diagnosed in a timely manner. The current TB diagnostic methods are subjective, inefficient, or not cost-effective. Antibody-based blood tests can be used efficiently and cost-effectively for TB diagnosis. A major challenge is that different TB patients ...201121976221
Purification and Characterization of an Endo-D: -arabinase Produced by Cellulomonas.An extracellular endo-D: -arabinase enzyme produced by the bacterial strain of Cellulomonas was purified 77.1-fold with 0.20% recovery for protein by DEAE Sepharose anion exchange, Sephacryl S-300 gel filtration and blue Sepharose affinity chromatography, and designated as CEDAase. The apparent molecular mass of CEDAase was 45 kDa determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CEDAase is an endoenzyme for arabinogalactan with the main and specific product of hexa-arabin ...201222120088
Identification of nontuberculous mycobacteria isolated from clinical sterile sites in patients at a university hospital in the city of Rio de Janeiro, Brazil.To identify nontuberculous mycobacteria (NTM) isolated from sterile sites in patients hospitalized between 2001 and 2006 at the Clementino Fraga Filho University Hospital, located in the city of Rio de Janeiro, Brazil.201121881743
Tuberculous meningitis in Greek children.Background: Tuberculous meningitis (TBM) is the most severe form of Mycobacterium tuberculosis infection. Our aim was to analyze the epidemiology, clinical features, diagnostic approach, and outcome of tuberculous meningitis in childhood. Methods: During a 25-y period (1984-2008), 43 children, aged 7 months to 13 y, were hospitalized in the Paediatric Department of the referral centre for infectious diseases in Thessaloniki, Greece with the diagnosis of TBM. The patients were classified accordin ...201122200165
Comparison of epitope specificity of anti-heat shock protein 60/65 IgG type antibodies in the sera of healthy subjects, patients with coronary heart disease and inflammatory bowel disease.Previously, we reported on the presence of antibodies to linear epitopes of human and mycobacterial 60 kD heat shock proteins (HSP) in the sera of healthy blood donors. Since many recent findings indicate that the levels of these antibodies may be altered in coronary heart disease (CHD) and also inflammatory bowel diseases (IBD), it seemed worthwhile to compare the epitope specificity of the anti-HSP60 and anti-HSP65 antibodies in the sera of patients with these diseases to those in healthy subj ...201122038196
Antibacterial activities of dendritic amphiphiles against nontuberculous mycobacteria.The anti-mycobacterial activities of nine series of dicarboxyl and tricarboxyl dendritic amphiphiles with one alkyl, two alkyl, and cholestanyl tails against Mycobacterium abscessus, Mycobacterium avium, Mycobacterium chelonae, Mycobacterium marinum and Mycobacterium smegmatis have been measured. The dendritic amphiphiles overcame the limited aqueous solubility of natural long-chain fatty acids, alcohols, and amines to enable profiling the susceptibilities of the different mycobacterial species ...201122209468
[latent tuberculosis among professionals with and without direct contact with inmates of two penitentiaries in the state of são paulo, brazil, 2008].for groups of persons who remain confined, mainly in prisons, tuberculosis has always been a serious health problem, due to its transmission respiratory, putting in risk the professionals that work in a prison, especially the communicants of inmates.201122069016
comparative analysis of mycobacterial nadh pyrophosphatase isoforms reveals a novel mechanism for isoniazid and ethionamide inactivation.nadh pyrophosphatase (nudc) catalyses the hydrolysis of nad(h) to amp and nmn(h) [nicotinamide mononucleotide (reduced form)]. nudc multiple sequence alignment reveals that homologues from most mycobacterium tuberculosis isolates, but not other mycobacterial species, have a polymorphism at the highly conserved residue 237. to elucidate the functional significance of this polymorphism, comparative analyses were performed using representative nudc isoforms from m. tuberculosis h37rv (nudc(rv)) and ...201122026918
immune interference in mycobacterium tuberculosis intracellular iron acquisition through siderocalin recognition of carboxymycobactins.the innate immune system antibacterial protein siderocalin (scn) binds ferric carboxymycobactin (cmb) and also several catecholate siderophores. although the recognition of catecholates by scn has been thoroughly investigated, the binding interactions of scn with the full spectrum of cmb isoforms have not been studied. here we show that scn uses different binding modes for the limited subset of bound cmb isoforms, resulting in a range of binding affinities that are much weaker than other siderop ...201121978368
therapeutic aerosol bioengineering of targeted, inhalable microparticle formulations to treat mycobacterium tuberculosis (mtb).therapeutic aerosol bioengineering (tab) of mycobacterium tuberculosis (mtb) therapies using inhalable microparticles offers a unique opportunity to target drugs to the site of infection in the alveolar macrophages, thereby increasing dosing in the lungs and limiting systemic exposure to often toxic drugs. previous work by us used sophisticated, high content analysis to design the optimal poly(lactide-co-glycolic) acid (plga) microparticle for delivery of drugs to alveolar macrophages. herein, w ...201122183789
bisubstrate adenylation inhibitors of biotin protein ligase from mycobacterium tuberculosis.the mycobacterial biotin protein ligase (mtbpl) globally regulates lipid metabolism in mtb through the posttranslational biotinylation of acyl coenzyme a carboxylases involved in lipid biosynthesis that catalyze the first step in fatty acid biosynthesis and pyruvate coenzyme a carboxylase, a gluconeogenic enzyme vital for lipid catabolism. here we describe the design, development, and evaluation of a rationally designed bisubstrate inhibitor of mtbpl. this inhibitor displays potent subnanomolar ...201122118677
novel phage amplified multichannel series piezoelectric quartz crystal sensor for rapid and sensitive detection of mycobacterium tuberculosis.the key factors that control the spread and mortality rate of tuberculosis (tb) are rapid detection and diagnosis. however, the current detection of mycobacterium tuberculosis (m. tuberculosis) cannot meet the recommended requirements for clinical diagnosis in turnaround time. in this paper, the feature of phage d29 that infects m. tuberculosis and mycobacterium smegmatis (m. smegmatis) was combined with the sensitivity of multichannel series piezoelectric quartz crystal sensor (mspqc) to detect ...201122142398
Structure and host recognition of serotype 13 glycopeptidolipid from Mycobacterium intracellulare.The Mycobacterium avium-M. intracellulare complex (MAIC) is divided into 28 serotypes by a species-specific glycopeptidolipid (GPL). Previously, we clarified the structures of serotype 7 GPL and two methyltransferase genes (orfA and orfB) in serotype 12 GPL. This study elucidated the chemical structure, biosynthesis gene, and host innate immune response of serotype 13 GPL. The oligosaccharide (OSE) structure of serotype 13 GPL was determined to be 4-2'-hydroxypropanoyl-amido-4,6-dideoxy-ß-hexose ...201121856857
Docking studies on Novel Analogues of 8 Methoxy Fluoroquinolones against GyrA Mutants of Mycobacterium tuberculosis.ABSTRACT: BACKGROUND: Fluoroquinolone resistance is a serious threat in the battle against the treatment of multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Fluoroquinolone resistant isolates from India had shown to have evolved several mutants in the quinolone resistance determining region (QRDR) of DNA gyrase A subunit (GyrA), the target of fluoroquinolone. In view of high prevalence of mutations in the 'hot spot' region, a study on combinatoria ...201122152119
Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis.OBJECTIVES: New classes of drugs are needed to treat tuberculosis (TB) in order to combat the emergence of resistance to existing agents and shorten the duration of therapy. Targeting DNA gyrase is a clinically validated therapeutic approach using fluoroquinolone antibiotics to target the gyrase subunit A (GyrA) of the heterotetramer. Increasing resistance to fluoroquinolones has driven interest in targeting the gyrase subunit B (GyrB), which has not been targeted for TB. The biological activiti ...201122052686
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