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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
Factors Associated With Misdiagnosis of Smear-Negative Tuberculosis: An Experience in Taiwan.BACKGROUND: A negative sputum smear from a patient with history, physical examination, and chest X-ray findings suggestive of tuberculosis (TB) presents a diagnostic dilemma. We investigated the possible factors associated with a misdiagnosis and inappropriate treatment of TB among such patients. METHODS: We reviewed the records of 193 patients whose diagnoses with TB included conflicting test results and were reported to the Taiwan CDC in 2004. When other conditions were found to underlie the i ...201122152195
[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
[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
synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds and their evaluation for tuberculostatic activity.a series of novel 3-cyclohexylpropanoic acid derivatives and 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been synthesized and evaluated for tuberculostatic activity. compounds 1a, 1c, 1e and 1f bearing benzimidazole or benzimidazole-like systems showed the most potent tuberculostatic activity against mycobacterium tuberculosis strains with mic values ranging from 1.5 to 12.5μg/ml. more importantly 1a (6-chloro-2-(2-cyclohexylethyl)-4-nitro-1h-benzo[d]imidazole) ...201222153872
Distinct polyfunctional CD4(+) T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy.Tuberculous pleurisy (TBP) is a frequent extrapulmonary manifestation characterized by the accumulation of inflammatory cells that can sometimes be spontaneously self-cured. To achieve a greater insight into T cells at a local site, we systematically characterized and compared the numbers of antigen-specific T cells responding to BCG- or MTB-specific antigens. Our results showed that significantly higher levels of Th1 cytokines were produced by pleural fluid cells (PFCs) than PBMCs following sti ...201122154006
a defect in the synthesis of interferon-γ by the t cells of complement-c5 deficient mice leads to enhanced susceptibility for tuberculosis.interferon-γ (ifnγ) plays a major role during host defense against mycobacterium tuberculosis (mtb). t cells produce ifnγ in response to il-12 and il-18 secreted from mtb infected macrophages. ifnγ in turn, induces nitric oxide secretion in macrophages that kills mtb. ifnγ knockout mice are thus hyper-susceptible to tuberculosis. we reported earlier that complement-c5 deficient (c5(-/-)) congenic mice are more susceptible to tuberculosis and showed reduced il-12 synthesis in their macrophages. u ...201122154007
a convenient synthesis of glucose monomycolate.an efficient synthesis of glucose monomycolate, an important lipidic antigen from mycobacterium tuberculosis is described.201122154492
[mycobacterium massiliense bone infection]. 201122154522
dynamic cross-talk among remote binding sites: the molecular basis for unusual synergistic allostery.allosteric regulation of protein function is critical for metabolic control. binding of allosteric effectors elicits a functional change in a remote ligand binding site on a protein by altering the equilibrium between different forms in the protein ensemble. 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (dah7ps) catalyzes the first step in the shikimate pathway, which is responsible for the biosynthesis of aromatic amino acids trp, phe, and tyr. feedback regulation by the aromatic amino a ...201122154807
synthesis and in vitro antimycobacterial activity of compounds derived from (r)- and (s)-2-amino-1-butanol - the crucial role of the configuration.the synthesis of 47 structurally diverse compounds incorporating the (r)-2-amino-1-butanol motif has been realized. ten of these compounds were found to exhibit in vitro specific activity against mycobacterium tuberculosis h37rv in a mic range of 0.65 μm-14.03 μm. five of the most active compounds 11, 22, 23, 31 and 42 (5.7-11.1 fold more active than ethambutol) can be outlined with very low cytotoxicity towards human embryonal kidney non-tumour cells (si ranging from 91.2 to 375.4). for the pur ...201122154833
ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and MAPK signaling.Macrophages, as sentinels of robust host immunity, are key regulators of innate immune responses against invading mycobacteria; however, pathogenic mycobacteria survive in the infected host by subverting host innate immunity. Infection dependent expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. As a part of multifaceted immunity to mycobacterial infection, ...201222154837
to tst or not to tst: is tuberculin skin testing necessary before bcg immunisation in children?bacille calmette-guérin (bcg) vaccine is one of the most commonly administered vaccines worldwide. in countries with high tb prevalence, it is generally given shortly after birth. in a number of low tb prevalence countries, bcg is used as a travel vaccine, typically given to children outside the neonatal period prior to visiting regions where tb is common. in this setting, it is recommended that latent tb infection (ltbi) resulting from prior exposure to mycobacterium tuberculosis is excluded by ...201122155145
A mechanism of action for small heat shock proteins.Molecular dynamics simulations of a fitted multimeric structure of Mycobacterium tuberculosis a-crystallin (Mtb Acr) identify solvent exclusion from the ß(4)-ß(8) hydrophobic groove as a critical factor driving subunit assembly. Dehydration is also implicated as a determinant factor governing the chaperone activity of the dimer upon its dissociation from the oligomer. Two exposed hydrogen bonds, responsible for stabilizing the ß(8)-ß(9) fold are identified as key mechanistic elements in this pro ...201122155251
espd is critical for the virulence-mediating esx-1 secretion system in mycobacterium tuberculosis.esx-1-mediated secretion in mycobacterium tuberculosis is dependent on proteins encoded by the co-transcribed espa-espc-espd gene cluster. while the roles of espa and espc with respect to the esx-1 secretion system have been actively investigated, the function of espd remains unknown. we show that espd is secreted by m. tuberculosis but, unlike espa and esxa, its export does not exclusively require the esx-1 system. evidence for stabilization of cellular levels of espa and espc by espd is presen ...201122155774
pharmacokinetics-pharmacodynamics of tmc207 and its n-desmethyl metabolite in a murine model of tuberculosis.tmc207 is a first in class diarylquinoline with a new mode of action against mycobacteria targeting the atp synthase. it is metabolized to an active derivative, n-desmethyl tmc207, and both compounds are eliminated with long terminal half-lives (50-60 hours in mice) reflecting slow release from tissues such as lung and spleen. in vitro, tmc207 is 5-fold more potent against mycobacterium tuberculosis than n-desmethyl tmc207, and the effects of the two compounds are additive. the pharmacokinetic-p ...201122155815
resuscitation-promoting factors are required for β-lactam tolerance and the permeability barrier in mycobacterium tuberculosis.mycobacterial resuscitation-promoting factors (rpfs) have been of great interest since the discovery that they promote the growth of non-culturable mycobacterium tuberculosis cells. yet, their precise role in mycobacterial survival and infection has remained elusive. we performed a chemical screen to identify molecules that show preferential killing of a mycobacterium tuberculosis mutant lacking rpfs over wild-type bacilli and found that the mutant has enhanced sensitivity to the β-lactam class ...201122155826
Structural activation of the transcriptional repressor EthR from Mycobacterium tuberculosis by single amino acid change mimicking natural and synthetic ligands.Ethionamide is an antituberculous drug for the treatment of multidrug-resistant Mycobacterium tuberculosis. This antibiotic requires activation by the monooxygenase EthA to exert its activity. Production of EthA is controlled by the transcriptional repressor EthR, a member of the TetR family. The sensitivity of M. tuberculosis to ethionamide can be artificially enhanced using synthetic ligands of EthR that allosterically inactivate its DNA-binding activity. Comparison of several structures of Et ...201122156370
Paradoxical Responses After Start of Antimicrobial Treatment in Mycobacterium ulcerans Infection.Background. Antimicrobial killing in mycobacterial infections may be accompanied by (transient) clinical deterioration, known as paradoxical reaction. To search for patterns reflecting such reactions in the treatment of Buruli ulcer (Mycobacterium ulcerans infection), the evolution of lesions of patients treated with antimicrobials was prospectively assessed.Methods. The lesion size of participants of the BURULICO antimicrobial trial (with lesions =10 cm cross-sectional diameter) was assessed by ...201122156855
recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent mycobacterium tuberculosis infection.preventing tuberculosis (tb) by treating latent mycobacterium tuberculosis infection (ltbi) is a cornerstone of the u.s. strategy for tb elimination. three randomized controlled trials have shown that a new combination regimen of isoniazid (inh) and rifapentine (rpt) administered weekly for 12 weeks as directly observed therapy (dot) is as effective for preventing tb as other regimens and is more likely to be completed than the u.s. standard regimen of 9 months of inh daily without dot. this rep ...201122157884
Seroprevalence of Mycobacterium avium subspecies paratuberculosis in elks in Korea. 201122158271
rv2468c, a novel mycobacterium tuberculosis protein that costimulates human cd4+ t cells through vla-5.mtb regulates many aspects of the host immune response, including cd4(+) t lymphocyte responses that are essential for protective immunity to mtb, and mtb effects on the immune system are paradoxical, having the capacity to inhibit (immune evasion) and to activate (adjuvant effect) immune cells. mtb regulates cd4(+) t cells indirectly (e.g., by manipulation of apc function) and directly, via integrins and tlrs expressed on t cells. we now report that previously uncharacterized mtb protein rv2468 ...201122158781
magnetic nanosensors for highly sensitive and selective detection of bacillus calmette-guérin.with current concerns of the global threat from tuberculosis, it has become important to rapidly identify the bacteria. traditional technologies involving isolation and amplification of the pathogenic bacteria are complicated and time-consuming. in this work, we describe a sensitive nmr-based detection method to identify bacteria via bacteria-induced self-assembly of magnetic nanoparticles. bacillus calmette-guérin (bcg) was used as a surrogate for mycobacterium tuberculosis. we prepared the pro ...201122158883
Drug susceptibility pattern of Mycobacterium tuberculosis isolates against conventional anti-tuberculosis drugs in Dhaka, Bangladesh. 201122159394
Utility of nitrate reductase assay for detection of multidrug-resistant Mycobacterium tuberculosis in a low resource setting.Introduction. The performance of a drug susceptibility test may change when moving from the research stage to implementation on a population level in actual public health practice. Objective. The performance of a rapid drug susceptibility test was described for detecting multidrug-resistant Mycobacterium tuberculosis when implemented in the routine workflow of a low-resource reference laboratory. Materials and methods. A prospective study was done comparing the performance of the nitrate reducta ...201122159543
polyclonal antibody against conserved sequences of mce1a protein blocks mtb infection in macrophages.the pathogenesis of mycobacterium tuberculosis is largely due to its ability to enter and survive within human macrophages. it is suggested that a specific protein namely mammalian cell entry protein is involved in the pathogenesis and the specific gene for this protein mce1a has been identified in several pathogenic organisms such as rickettsia, shigella, escherichia coli, helicobacter, streptomyces, klebsiella, vibrio, neisseria, rhodococcus, nocardioides, saccharopolyspora erthyrae, and pseud ...201122159737
molecular genetic analysis of mycobacterium tuberculosis strains spread in different patient groups in st. petersburg, russia.molecular epidemiological features of mycobacterium tuberculosis strains among different patient groups in russia have not been studied well. the aim of our study was to compare the genotypes of m. tuberculosis strains circulating among tuberculosis (tb) patients from different groups: homeless, human immunodeficiency virus (hiv)-infected, prisoners, and the general population of st. petersburg citizens. one hundred and forty-two m. tuberculosis complex isolates from different tb patient groups ...201122160887
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
multiplex real-time pcr assay and melting curve analysis for identifying mycobacterium tuberculosis complex and nontuberculous mycobacteria.a multiplex real-time pcr assay and melting curve analysis for identifying 23 mycobacterial species was developed and evaluated using 77 reference strains and 369 clinical isolates. concordant results were obtained for all 189 (100%) isolates of mycobacterium tuberculosis complex and 169 (93.9%) isolates of nontuberculous mycobacteria. our results showed that this multiplex real-time pcr assay is an effective tool for the mycobacterial identification from cultures.201122162553
direct drug susceptibility testing of mycobacterium tuberculosis for rapid detection of multi-drug resistance using bactec™ mgit 960 system; a multi-center study.conventional indirect drug susceptibility testing of mycobacterium tuberculosis with liquid medium is well-established and offers time saving and reliable results. this multi-center study was carried out to evaluate if drug susceptibility testing (dst) can be successfully carried out directly from processed smear-positive specimens (direct dst) and if this approach would offer substantial time saving.sputum specimens were digested, decontaminated, and concentrated by the laboratory routine proce ...201122162558
effectiveness of an integrated real-time pcr method for detection of the mycobacterium tuberculosis complex in smear-negative extrapulmonary samples in an area of low tuberculosis prevalence.early extrapulmonary tuberculosis (eptb) diagnosis is particularly difficult. among 108 smear-negative extrapulmonary samples showing a positive culture for mycobacterium tuberculosis complex (43 body fluids and 65 nonliquid specimens), 63 (58.3%) were positive with the xpert mtb/rif assay (gx). gx sensitivity was quite low for samples from sterile locations (especially for pleural fluids: 26.9%) but high for some nonliquid samples, like abscess aspirates (76.5%). in summary, gx may be a useful ...201122162564
atypical cause of prolonged myelosuppression.we present the case of a 57-year-old male with poor prognosis (trisomy 21 and monosomy 7) acute myeloid leukaemia (aml) who presented with rigors and fever during cytogenetic remission. peripheral and central line blood cultures were positive for mycobacterium chelonae and he commenced empiric treatment with meropenem, amikacin, clarithromycin and ciprofloxacin. it appears that m chelonae infection was responsible for persistent myelosuppression after expected recovery from chemotherapy, which s ...200922162739
BCG Induces Protection against Mycobacterium tuberculosis Infection in the Wistar Rat Model.Our understanding of the correlation of Mycobacterium bovis Bacille Calmette-Guerin (BCG)-mediated immune responses and protection against Mycobacterium tuberculosis (Mtb) infection is still limited. We have recently characterized a Wistar rat model of experimental tuberculosis (TB). In the present study, we evaluated the efficacy of BCG vaccination in this model. Upon Mtb challenge, BCG vaccinated rats controlled growth of the bacilli earlier than unvaccinated rats. Histopathology analysis of i ...201122162757
SNP/RD Typing of Mycobacterium tuberculosis Beijing Strains Reveals Local and Worldwide Disseminated Clonal Complexes.The Beijing strain is one of the most successful genotypes of Mycobacterium tuberculosis worldwide and appears to be highly homogenous according to existing genotyping methods. To type Beijing strains reliably we developed a robust typing scheme using single nucleotide polymorphisms (SNPs) and regions of difference (RDs) derived from whole-genome sequencing data of eight Beijing strains. SNP/RD typing of 259 M. tuberculosis isolates originating from 45 countries worldwide discriminated 27 clonal ...201122162765
Local Ischemia and Increased Expression of Vascular Endothelial Growth Factor Following Ocular Dissemination of Mycobacterium tuberculosis.The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ~200 bacill ...201122162767
genome-wide sequence variation among mycobacterium avium subspecies paratuberculosis isolates: a better understanding of johne's disease transmission dynamics.mycobacterium avium subspecies paratuberculosis (m. ap), the causative agent of johne's disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. to better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several m. ap and m. avium subspecies avium (m. avium) isolates to gain insights into genomic diversity associated with variable hosts and environments. using next-generation sequencing technology, all six m ...201122163226
Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection.Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Baye ...201122164200
Glutathione and Adaptive Immune Responses against Mycobacterium tuberculosis Infection in Healthy and HIV Infected Individuals.Glutathione (GSH), a tripeptide antioxidant, is essential for cellular homeostasis and plays a vital role in diverse cellular functions. Individuals who are infected with Human immuno deficiency virus (HIV) are known to be susceptible to Mycobacterium tuberculosis (M. tb) infection. We report that by enhancing GSH levels, T-cells are able to inhibit the growth of M. tb inside macrophages. In addition, those GSH-replenished T cell cultures produced increased levels of Interleukin-2 (IL-2), Interl ...201122164280
discovery of novel mdr-mycobacterium tuberculosis inhibitor by new frigate computational screen.with 1.6 million casualties annually and 2 billion people being infected, tuberculosis is still one of the most pressing healthcare challenges. here we report on the new computational docking algorithm frigate which unites continuous local optimization techniques (conjugate gradient method) with an inherently discrete computational approach in forcefield computation, resulting in equal or better scoring accuracies than several benchmark docking programs. by utilizing frigate for a virtual screen ...201122164290
Lipoglycans contribute to innate immune detection of mycobacteria.Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infec ...201122164297
Clinico-microbiological profile and treatment outcome of infectious scleritis: experience from a tertiary eye care center of India.Medical and microbiology records of seventeen patients (17 eyes), diagnosed as scleritis of infectious origin were reviewed; to study clinical features, predisposing risk factors, microbiologic profile and treatment outcome of infectious scleritis. The mean patient age was 52.3 ± 19.75 years. Twelve patients (70.6%) had history of trauma/prior surgery. Isolated organisms included Staphylococcus species (spp) (n = 5), Fungus (n = 4), Nocardia spp (n = 3), two each of atypical Mycobacterium spp an ...201222164345
Circulating levels of Insulin-like Growth Factor-I (IGF-I) correlate with disease status in leprosy.ABSTRACT: BACKGROUND: Caused by Mycobacterium leprae (ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocr ...201122166091
[Intracranial tuberculoma simulating a malignant tumor: Case report and literature review.]INTRODUCTION. Extrapulmonary manifestations of tuberculosis involving the central nervous system (CNS) due to haematogenous spread are not a rare entity. Tuberculoma is a granulomatous inflammatory process mimicking in rare occasions a malignant neoplasm radiologically. The authors report a case of a giant right frontal tuberculoma mimicking a malignant tumor and review the literature. CASE REPORT. A sixtyfour-year-old women with several weeks of headache and behavior alterations admitted at the ...201122167292
[In Process Citation]. 201122168006
[Regeneration of transgenic plants from Cichorium intybus L. var. foliosum Hegi hairy roots].Transgenic plants were regenerated from Cichorium intybus L. hairy roots transformed with genes of tuberculosis antigenes ESAT6 and Ag85B or human interferon alpha2b. The plant regeneration was light-dependent and occurred on the media without growth regulators. The DNA PCR and RT-PCR analyses have shown the presence and expression both selective and target genes in all root lines and regenerated plants.201122168044
frequencies of mica alleles in patients from southern brazil with multibacillary and paucibacillary leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae, which mainly affects the skin and nervous system. the disease has several clinical forms. this study investigated the mica and hla-b genes in 223 samples from leprosy patients and 201 samples from healthy individuals matched for age, gender and ethnical background. of the patients, 153 had multibacillary, 45 paucibacillary and 25 indeterminate leprosy. the aim of this case-control study was to assess whether the mica alleles ...201122168250
[paying attention to non-tuberculous mycobacterium in the diagnosis and treatment of lung diseases]. 201122168974
[pulmonary infection with mycobacterium massiliense: a case report and review of the literature].to analyze the clinical features and differential diagnosis of pulmonary infection with mycobacterium massiliense (m. massiliense).201122168976
[Evaluation of the mycobactericidal efficacy of linezolid in vitro].To evaluate the mycobactericidal efficacy of linezolid to Mycobacterium tuberculosis bacilli and Non-tuberculous mycobacteria (NTM) in vitro, and to analyze the interaction between linezolid and other anti-TB drugs in vitro.201122168977
[in vitro activities of clofazimine against different drug-resistant types of mycobacterium tuberculosis].to study the in vitro antituberculous activities of clofazimine (clf) to different drug-resistant types of mycobacterium tuberculosis.201122168978
bcg vaccination of neonatal calves: potential roles for innate immune cells in the induction of protective immunity.bovine tuberculosis is a disease of increasing incidence in the uk causing major economic losses and with significant impact on bovine and, potentially human health: the causative agent mycobacterium bovis is a zoonotic pathogen. neonatal vaccination with the attenuated m. bovis bacille calmette guerin (bcg) vaccine confers a significant degree of protection in cattle, and is a widely used control strategy for human tb. the adaptive immune system is relatively immature in neonates and increased ...201122169020
outcomes of toll-like receptors' antagonism in steroid-resistant optic neuritis; a pilot study.background: to investigate the safety and outcomes of off-label immunomodulator mycobacterium w. (mw), a tlr 9 antagonist in steroid-resistant idiopathic unilateral optic neuritis. methods: case series. eight patients with documented idiopathic unilateral optic neuritis who did not improve with methyl prednisolone followed by oral steroids as per the optic neuritis treatment trial (ontt) were administered mw 5 ml ...201122169982
is continuation of anti-tumor necrosis factor-α therapy a safe option for patients who have developed pulmonary mycobacterial infection? : case presentation and literature review.continuation of anti-tumor necrosis factor-α (tnfα) therapy generally has not been recommended for patients who have developed nontuberculous mycobacterial (ntm) diseases; in daily practice, however, we often encounter patients with refractory rheumatoid arthritis (ra) who experience uncontrollable flares following withdrawal of anti-tnfα agents. here, we report a case of pulmonary ntm disease caused by mycobacterium intracellulare occurring in a patient with refractory ra undergoing etanercept ...201122170032
epiregulin (ereg) variation is associated with susceptibility to tuberculosis.although host genetics influences susceptibility to mycobacterium tuberculosis, the human genes regulating pathogenesis remain largely unknown. we used m. tuberculosis-stimulated macrophage gene expression profiling in conjunction with a case-control genetic association study to discover epiregulin (ereg), as a novel candidate tuberculosis (tb) susceptibility gene. using a genome-wide association study dataset, we found that among the 21 genes with greater than 50-fold induction, ereg had the mo ...201122170233
[Multi-resistant tuberculosis at the hôpital d'instruction des armées de Libreville (Gabon) about 16 cases.]According to WHO estimates, between 1 and 20% of tuberculosis cases in the world are multiresistant. In Gabon, this prevalence is estimated at 1.9%. In this forward-looking study from March 2006 to August 2010, we report 16 cases of multi-resistant tuberculosis out of 24 suspected resistant samples (persistence of the clinical and radiological signs after three months of well conducted treatment with first-line anti-tuberculous drugs). This study is realized in association with the laboratory of ...201122170406
osteomyelitis of the spine caused by mycobacterium avium complex in an immunocompetent patient. 201122170522
molecular characteristics of rifampin and isoniazid resistant mycobacterium tuberculosis strains isolated in vietnam.molecular characterization of drug resistance of mycobacterium tuberculosis strains of different origins can generate information that is useful for developing molecular methods. these methods are widely applicable for rapid detection of drug resistance. a total of 166 rifampin (rif) and/or isoniazid (inh) resistant strains of mycobacterium tuberculosis have been isolated from different parts of vietnam, they were screened for mutations associated with resistance to these drugs by sequence analy ...201122170905
first worldwide proficiency study on variable numbers of tandem repeats typing of mycobacterium tuberculosis complex strains.although variable numbers of tandem repeats (vntr) typing has gained recognition as the new standard for dna fingerprinting of mycobacterium tuberculosis complex (mtbc) isolates, external quality control programs have not yet been developed. therefore, we organized the first multi-center proficiency study on 24-locus vntr typing. sets of 30 dnas of mtbc strains, including ten duplicate dna samples, were distributed among 37 participating laboratories in 30 different countries worldwide. twenty-f ...201122170917
real-time pcr and high resolution melt analysis for rapid detection of mycobacterium leprae drug resistance mutations and strain types.drug resistance surveillance and strain typing of mycobacterium leprae are necessary to investigate ongoing transmission of leprosy in endemic regions. to enable wider implementation of these molecular analyses, novel real time-pcr-high resolution melt (rt-pcr-hrm) assays without allele specific primers or probes and post pcr sample handling were developed. for the detection of mutations within drug resistance determining regions (drdrs) of folp1, rpob and gyra, targets for dapsone, rifampicin a ...201122170923
real-time pcr of mycobacteriophage for rapid phenotypic drug susceptibility results for m. tuberculosis.managing drug resistant mycobacterium tuberculosis (tb) requires drug susceptibility testing, yet conventional drug susceptibility testing is slow and molecular testing does not yield results for all antituberculous drugs. we addressed these challenges by utilizing real-time pcr of mycobacteriophage d29 dna to evaluate the drug resistance of clinical tb isolates. mycobacteriophages infect and replicate in viable bacterial cells faster than bacteria cells replicate, and have been used for detecti ...201122170929
the population structure of multi- and extensively drug-resistant tuberculosis in south africa.genotyping of multidrug-resistant (mdr) mycobacterium tuberculosis strains isolated from tuberculosis (tb) patients in four south african provinces (western cape, eastern cape, kwazulu-natal and gauteng) revealed a distinct population structure of the mdr strains in all four regions despite the evidence of substantial human migration between these settings. in all analyzed provinces, a negative correlation between strain diversity and an increasing level of drug resistance (from mdr-tb to extens ...201122170931
[A case of lung cancer complicated with active non-tuberculous mycobacterium (NTM) infection successfully treated with anti-cancer agents and anti-NTM agents].A 55-year-old man with pulmonary Mycobacterium avium complex (MAC) disease was referred to our hospital with dyspnea on exertion and general fatigue. Chest computed tomography (CT) revealed a nodular shadow with pleural indentation in the left S(1+2), left pleural effusion, and a thick-walled cavitary lesion due to pulmonary MAC disease in the right S1. A biopsy specimen of the nodule in the left S(1+2) revealed adenocarcinoma, which various examinations confirmed to be stage IV lung adenocarcin ...201122171491
[on: three cases of uveitis induced by mycobacteriosis therapy using rifabutin]. 201122171511
specificity of the tuberculin skin test and the t-spot.tb assay among students in a low-tuberculosis incidence setting.abstract objective: interferon-γ release assays (igras) are an important tool for detecting latent mycobacterium tuberculosis infection (ltbi). insufficient data exist about igra specificity in college health centers, most of which screen students for ltbi using the tuberculin skin test (tst). participants: students at a low-tb incidence college health center. methods: tst and t-spot.tb were performed on prospectively recruited students. tb exposure risk was assessed using a questionnaire: th ...201222171735
redox homeostasis in mycobacteria: the key to tuberculosis control?mycobacterium tuberculosis (mtb) is a metabolically flexible pathogen that has the extraordinary ability to sense and adapt to the continuously changing host environment experienced during decades of persistent infection. mtb is continually exposed to endogenous reactive oxygen species (ros) as part of normal aerobic respiration, as well as exogenous ros and reactive nitrogen species (rns) generated by the host immune system in response to infection. the magnitude of tuberculosis (tb) disease is ...201122172201
Humans as Source of Mycobacterium tuberculosis Infection in Cattle, Spain.TO THE EDITOR: Mycobacterium tuberculosis is the main causative agent of tuberculosis in humans. However, little attention has been paid to its transmission from humans to animals. We report M. tuberculosis infections in 3 cattle farms in Spain. The epidemiologic investigation traced humans as the source of infection, with 1 of the strains showing multidrug resistance.201122172249
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
Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility.Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacteri ...201122174129
Correlation of the phenotypic ethambutol susceptibility of Mycobacterium tuberculosis with embB gene mutations in Korea.The phenotypic resistance of ethambutol (EMB) in Mycobacterium tuberculosis with embB gene mutations is still obscure. This study was designed to better understand the EMB resistance due to the embB gene mutation. Sequencing analysis of the embB gene was performed for the 124 EMB susceptible and 93 EMB resistant M. tuberculosis strains isolated from South Korea. The minimum inhibitory concentration (MIC) was determined in EMB susceptible M. tuberculosis strains with the embB mutation and wildtyp ...201122174373
The use of adenosine deaminase measurements and QuantiFERON in the rapid diagnosis of tuberculous peritonitis.Peritoneal tuberculosis (TB) is a considerable problem in certain developing nations. Current diagnostic tests for peritoneal TB are difficult and time-consuming. This study aimed to determine the effectiveness of an adenosine deaminase (ADA) assay and the QuantiFERON-Gold (QFT-G) assay in the rapid diagnosis of TB peritonitis. Forty-one patients with a presumptive diagnosis of TB peritonitis with ascites were admitted to Mansoura University Hospital and included in the study. Ascitic fluid and ...201122174374
nitrate reduction pathways in mycobacteria and theirimplications during latency.mycobacterial persistence has gained a lot of attention with respect to developing novel antitubercular drug, which could drastically reduce the duration of tuberculosis therapy. a better understanding of the physiology of mycobacterium tuberculosis, and metabolic state of the bacillus during the latent period is primary need to find drug targets against the persistent tb. recent biochemical and genetic studies of nitrate reduction in mycobacteria have revealed the role of distinct proteins and ...201122174380
Recombinant MPT83 Derived from Mycobacterium tuberculosis Induces Cytokine Production and Upregulates the Function of Mouse Macrophages through TLR2.TLR2 recognizes components of Mycobacterium tuberculosis and initiates APC activities that influence both innate and adaptive immunity. M. tuberculosis lipoproteins are an important class of TLR2 ligands. In this study, we focused on recombinant MPT83 (rMPT83) to determine its effects on mouse macrophages. We demonstrated that rMPT83 induced the production of TNF-a, IL-6, and IL-12 p40 and that cytokine induction depended on activated MAPKs, because we observed the rapid phosphorylation of ERK1/ ...201122174456
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
predictors of virologic failure in hiv/aids patients treated with highly active antiretroviral therapy in brasília, brazil during 2002-2008.little data exists concerning the efficacy of the antiretroviral therapy in the federal district in brazil, therefore in order to improve hiv/aids patients' therapy and to pinpoint hot spots in the treatment, this research work was conducted. of 139 hiv/aids patients submitted to the highly active antiretroviral therapy, 12.2% failed virologically. the significant associated factors related to unresponsiveness to the lentiviral treatment were: patients' place of origin (or = 3.28; ic95% = 1.0-9. ...201122174569
Targeting of Mycobacterium tuberculosis Heparin-Binding Hemagglutinin to Mitochondria in Macrophages.Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a virulence factor involved in extrapulmonary dissemination and a strong diagnostic antigen against tuberculosis, is both surface-associated and secreted. The role of HBHA in macrophages during M. tuberculosis infection, however, is less well known. Here, we show that recombinant HBHA produced by Mycobacterium smegmatis effectively induces apoptosis in murine macrophages. DNA fragmentation, nuclear condensation, caspase activation, ...201122174691
Chimeras of Escherichia coli and Mycobacterium tuberculosis Single-Stranded DNA Binding Proteins: Characterization and Function in Escherichia coli.Single stranded DNA binding proteins (SSBs) are vital for the survival of organisms. Studies on SSBs from the prototype, Escherichia coli (EcoSSB) and, an important human pathogen, Mycobacterium tuberculosis (MtuSSB) had shown that despite significant variations in their quaternary structures, the DNA binding and oligomerization properties of the two are similar. Here, we used the X-ray crystal structure data of the two SSBs to design a series of chimeric proteins (mß1, mß1'ß2, mß1-ß5, mß1-ß6 an ...201122174737
Epidemiological, clinical, and therapeutic pattern of Mycobacterium marinum infection: A retrospective series of 35 cases from southern France. 201222177650
Distribution of mycobacterial antigen based on differences of histological characteristics in pulmonary Mycobacterium avium infectious diseases-Consideration of the extent of surgical resection from the pathological standpoint.Quantitative assessment of mycobacterial antigens is very important to determine the surgical indication, as well as the area of resection for pulmonary Mycobacterium avium complex (MAC) infectious disease. However, at present, pathological assessment is only possible as a postoperative examination. We performed quantitative evaluation of mycobacterial antigens using lung tissues with MAC pulmonary infection obtained from surgical resection. The distribution of mycobacterial antigens was evaluat ...201122177729
multiple strains of mycobacterium bovis revealed by molecular typing in a herd of cattle.mycobacterium bovis isolates from an outbreak of bovine tuberculosis in a herd of cattle in rio de janeiro, brazil, were analysed by spoligotyping and variable-number tandem repeat pcr analysis of the mycobacterial interspersed repetitive unit and exact tandem repeats. molecular typing revealed a high genetic diversity of strains in the herd. the genetic diversity could be explained by the introduction of infected animals from different sources.201122178356
Antimycobacterial activities of 5-alkyl (or halo)-3'-substituted pyrimidine nucleoside analogs.Several 5-alkyl (or halo)-3'-azido (amino or halo) analogs of pyrimidine nucleosides have been synthesized and evaluated against Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium. Among these compounds, 3'-azido-5-ethyl-2',3'-dideoxyuridine (3) was found to have significant antimycobacterial activities against M. bovis (MIC(50)=1µg/mL), M. tuberculosis (MIC(50)=10µg/mL) and M. avium (MIC(50)=10µg/mL).201122178557
Comparative analyses of transport proteins encoded within the genomes of Mycobacterium tuberculosis and Mycobacterium leprae.The co-emergence of multidrug resistant pathogenic bacterial strains and the HIV pandemic has made tuberculosis a leading public health threat. The causative agent is Mycobacterium tuberculosis (Mtu), a facultative intracellular parasite. Mycobacterium leprae (Mle), a related organism that causes leprosy, is an obligate intracellular parasite. Given that different transporters are required for bacterial growth and persistence under a variety of growth conditions, we conducted comparative analyse ...201122179038
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
suspicion of mycobacterium avium subsp. paratuberculosis transmission between cattle and wild-living red deer (cervus elaphus) by multi target genotyping.for epidemiological tracing of paratuberculosis (johne's disease), multi-target genotyping of the etiologic agent mycobacterium avium subsp. paratuberculosis (map) is necessary. the study was undertaken to assess the informative value of different typing techniques and individual genome markers by investigation of map transmission between wild-living red deer and farmed cattle with known shared habitats.53 map-type-ii-isolates were differentiated by short-sequence repeat (ssr, 4 loci)-, mycobact ...201122179249
otomastoiditis with acute left facial nerve paralysis caused by mycobacterium chelonae.mycobacterium chelonae usually causes soft-tissue and skin infection. it is a rare cause of otomastoiditis. the clinical presentation and operative findings are similar to those of other nontuberculous mycobacterial infections. we describe a case of left-sided otomastoiditis with acute facial nerve paralysis caused by this organism in a previously well middle-aged woman. her facial palsy totally resolved after tympanomastoidectomy plus a 7-week regimen of clarithromycin and moxifloxacin. to our ...201122180118
Granuloma transplantation: an approach to study mycobacterium-host interactions.The host-pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host-pathogen relationship. Here, we review the development, application, ...201122180751
complete genome sequence of mycobacterium sp. strain (spyr1) and reclassification to mycobacterium gilvum spyr1.mycobacterium sp.spyr1 is a newly isolated strain that occurs in a creosote contaminated site in greece. it was isolated by an enrichment method using pyrene as sole carbon and energy source and is capable of degrading a wide range of pah substrates including pyrene, fluoranthene, fluorene, anthracene and acenapthene. here we describe the genomic features of this organism, together with the complete sequence and annotation. the genome consists of a 5,547,747 bp chromosome and two plasmids, a lar ...201122180818
new insights into the pathogenesis of tuberculosis revealed by mycobacterium marinum: the zebrafish model from the systems biology perspective.tuberculosis remains a worldwide health concern, largely due to the emergence of multi-drug-resistant (mdr) and extensive-drug-resistant (xdr) mycobacterium tuberculosis co-infection with hiv. the exact mechanism of mycobacterium virulence, pathogenesis, and persistence is not fully understood. the hallmark of tuberculosis, granulomas are promoted by mycobacterium virulence factors, and they have long been considered a structural advantage to the host. however, this traditional view has been cha ...201122181703
mycobacterium tuberculosis proteases and implications for new antibiotics against tuberculosis.tuberculosis remains a global health concern. effective novel therapeutics are urgently needed to tackle the inexorable increase of multidrug resistant and extensively drug-resistant strains and hiv coinfection. most proteases are important for mycobacterium tuberculosis virulence involving in the evasion or subversion of host defenses and/or tissue degradation, therefore they are ideal candidates for new drug targets. to explore this possibility, we summarize the functions of mycobacterium tube ...201122181704
evaluation of a lateral flow assay for the diagnosis of mycobacterium bovis infection in dairy cattle.a commercially available multi-antigen lateral flow assay (lfa) for detection of antibodies to mycobacterium bovis was evaluated by testing dairy cattle in baja california, méxico. sera and tissue samples were obtained from 268 dairy cattle at a slaughterhouse and were tested by lfa, bacteriological culture, and polymerase chain reaction (pcr). of 107 culture positive samples, 70 (65.4%) were positive by pcr and 49 (45.8%) were positive by lfa. the pcr and lfa gave positive results with an addit ...201222181821
CZE-ESI-MS/MS as an alternative proteomics platform to UPLC-ESI-MS/MS for samples of intermediate complexity.We demonstrate the use of capillary zone electrophoresis with an electrokinetically pumped sheath-flow electrospray interface for the analysis of a tryptic digest of a sample of intermediate protein complexity, the secreted protein fraction of Mycobacterium marinum. For electrophoretic analysis, 11 fractions were generated from the sample using reversed phase liquid chromatography; each fraction was analyzed by CZE-ESI-MS/MS, and 334 peptides corresponding to 140 proteins were identified in 165 ...201122182061
mycobacterium marinum infections in humans and tracing of its possible environmental sources.the low frequency of nontuberculous mycobacterial infections, nonspecific symptoms for individual mycobacteria, and the lack of specific identification methods could alter correct diagnosis. this study presents a combined microbiology and molecular-based approach for mycobacterium marinum detection in four aquarists with cutaneous mycobacterial infection. simultaneously, ecology screening for m. marinum presence in the aquarists' fish tanks was performed. a total of 38 mycobacterial isolates o ...201122182182
identification of the subcellular localization of mycobacterial proteins using localization motifs.mycobacterium, the most common disease-causing genus, infects billions of people and is notoriously difficult to treat. understanding the subcellular localization of mycobacterial proteins can provide essential clues for protein function and drug discovery. in this article, we present a novel approach that focuses on local sequence information to identify localization motifs that are generated by a merging algorithm and are selected based on a binomially distributed model. these localization mot ...201122182488
genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with mycobacterium bovis reveals suppression of host immune genes.abstract: background: mycobacterium bovis is the causative agent of bovine tuberculosis (btb), a pathological infection with significant economic impact. recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to m. bovis infection. furthermore, these studies may enable the identification of novel transcriptional markers of btb that can augment current diagnostic tests and surveillance programmes. in the pr ...201122182502
multi-centre evaluation of the speed-oligo mycobacteria assay for differentiation of mycobacterium spp. in clinical isolates.abstract: background: a new dna line probe assay (speed-oligo mycobacteria, vircell) has been launched for rapid differentiation of mycobacterium spp. from cultures. compared to other line-probe assays, speed-oligo mycobacteria covers a relatively limited spectrum of species but uses a simpler and faster dip-stick technique. the present multi-centre, multi-country study aimed at evaluating the utility and usability of speed-oligo mycobacteria in routine mycobacteriology diagnostics.results from ...201122182531
The relative frequency of Mycobacterium tuberculosis and Mycobacterium avium infections in HIV positive patients, Ahvaz, Iran.To estimate the prevalence of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium avium (M. avium) infections in HIV-positive patients suspected to have pulmonary and extrapulmonary mycobacterial co-infection using PCR technique.201222182648
straightforward palladium-mediated synthesis and biological evaluation of benzo[j]phenanthridine-7,12-diones as anti-tuberculosis agents.in 1991, who recognized the resurgence of tuberculosis as a global health problem. although modern chemotherapy is effective against the causative pathogen mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. the success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs. benzo[j]phenanthridine-7,12-diones, tetracyclic derivatives of the natural product benz[g]isoquinoline-5,10-dione, were ...201122182928
early diagnosis of relapse in borderline leprosy: two case reports.two cases of relapse in borderline leprosy were reported. despite the late-reversal, reaction-like feature, the suspicion of relapse in both was based on persistent and slow-developing skin lesions and an absence of acute neuritis or reaction during one year of follow-up. the authors have considered this possible occurrence in lepromatous borderline-treated patients after their immune cellular restoration and defend that not all type 1 reactions would be an inflammatory answer to persistent myco ...201122183459
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
Global Chemical Composition and Antioxidant and Anti-Tuberculosis Activities of Various Extracts of Globularia alypum L. (Globulariaceae) Leaves.In this work, an evaluation of the biological activities of Globularia alypum L. extracts and their global chemical composition was realized. Extracts from G. alypum were obtained by two extraction methods. The composition of polyphenols (8.5-139.95 g gallic acid equivalent/Kg of dry mass), tannins (1.39-18.65 g catechin equivalent/Kg of dry mass), anthocyanins (8.17-70.69 mg cyanidin equivalent/Kg of dry mass) and flavonoids (0.31-19.28 g quercetin equivalent/Kg of dry mass) was evaluated. The ...201122183884
non-tuberculous mycobacterial infections in the scottish borders: identification, management and treatment outcomes - a retrospective review.non-tuberculous mycobacteria are opportunist pathogens increasingly recognised as a cause of pulmonary and extrapulmonary disease. treatment is complicated, prolonged and potentially toxic, and due to a limited evidence base, potentially contentious and idiosyncratic. this is a retrospective review of non-tuberculous mycobacteria cases in the nhs borders health board between 1992 and 2010. we consider incidence, species identified, drug sensitivity testing and treatment outcome with reference to ...201122184566
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