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identification of mycobacterium cosmeticum sp. as a novel colitogenic infectious agent in a nonimmunocompromised patient. 201121739530
tuberculosis: an unpredictable long-standing human companion still in need of rapid diagnostic tests. 201121682799
[preparation and characterization of reference samples of mycobacterium tuberculosis culture filtrate protein-10 for time-resolved fluoroimmunoassay].to prepare reference samples of mycobacterium tuberculosis culture filtrate protein-10 (cfp-10) and cfp10-streptavidin fusion proteins (cfp10/sa) for time-resolved fluoroimmunoassay (trfia).201121690044
High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv.Kinase targets are being pursued in a variety of diseases beyond cancer, including immune and metabolic as well as viral, parasitic, fungal and bacterial. In particular, there is a relatively recent interest in kinase and ATP-binding targets in Mycobacterium tuberculosis in order to identify inhibitors and potential drugs for essential proteins that are not targeted by current drug regimens. Herein, we report the high throughput screening results for a targeted library of approximately 26,000 co ...201121708485
synthesis of various 3-nitropropionamides as mycobacterium tuberculosis isocitrate lyase inhibitor.various 3-nitropropionamides were synthesized and evaluated for in vitro activities against log and starved phase culture of two mycobacterial species and mycobacterium tuberculosis (mtb) isocitrate lyase (icl) enzyme inhibition studies. among 22 compounds, 1-cyclopropyl-7-(3,5-dimethyl-4-(3-nitropropanoyl)piperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (22) was found to be the most active compound in vitro with mics of 0.16 and 0.04++m against log- and starved-ph ...201121840711
[three cases of mycobacterium kansasii pulmonary diseases in previously healthy young women].mycobacterium kansasii pulmonary diseases account for 20% of cases of non-tuberculous mycobacteria. most patients are male. however, a recent study has found that radiological examinations in female patients often reveal nodular, bronchiectatic opacities. we describe 3 young women with cavitary opacities. patient 1 was a 35-year-old woman in whom thin-walled cavitary opacities were detected in the upper lobe during a routine checkup. sputum examination and fiberoptic bronchoscopy led to a diagno ...201121735743
monoclonal antibodies bind a snp-sensitive epitope that is present uniquely in mycobacterium avium subspecies paratuberculosis.due to a close genetic relatedness, there is no known antibody that detects mycobacterium avium subspecies paratuberculosis (map), which causes johne's disease in cattle and sheep, and does not cross-react with other m. avium subspecies. in the present study, a monoclonal antibody (mab; 17a12) was identified from mice immunized with a cell membrane fraction of map strain k-10. this antibody is 100% specific as it detected a 25-kda protein in all 29 map whole cell lysates, but did not bind to any ...201121845186
[cutaneous neutrophils infiltrates. case 2. erythema elevatum diutinum, late stage]. 201121736997
isoniazid proliposome powders for inhalation-preparation, characterization and cell culture studies.the aims of this study were to develop proliposome powders containing isoniazid (inh) in a dry powder aerosol form. inh-proliposome powders were prepared by a spray drying method. proliposome physicochemical properties were determined using cascade impactor, x-ray diffraction and differential scanning calorimetry. the toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (am) were determined. free inh and inh- ...201121845086
Latent tuberculosis: what the host "sees"?Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is the most successful pathogen of mankind and remains a major threat to global health as the leading cause of death due to a bacterial pathogen. Yet 90-95% of those who are infected with MTB remain otherwise healthy. These people are classified as "latently infected," but remain a reservoir from which active TB cases will continue to develop ("reactivation tuberculosis"). Latent infection is defined by the absence of cl ...201121717066
innate and adaptive interferons suppress il-1α and il-1β production by distinct pulmonary myeloid subsets during mycobacterium tuberculosis infection.interleukin-1 (il-1) receptor signaling is necessary for control of mycobacterium tuberculosis (mtb) infection, yet the role of its two ligands, il-1α and il-1β, and their regulation in vivo are poorly understood. here, we showed that both il-1α and il-1β are critically required for host resistance and identified two multifunctional inflammatory monocyte-macrophage and dc populations that coexpressed both il-1 species at the single-cell level in lungs of mtb-infected mice. moreover, we demonstra ...201122195750
molecular basis of the functional divergence of fatty acyl-amp ligase biosynthetic enzymes of mycobacterium tuberculosis.activation of fatty acids as acyl-adenylates by fatty acyl-amp ligases (faals) in mycobacterium tuberculosis is a variant of a classical theme that involves formation of acyl-coa (coenzyme a) by fatty acyl-coa ligases (facls). here, we show that faals and facls possess similar structural fold and substrate specificity determinants, and the key difference is the absence of a unique insertion sequence in facl13 structure. a systematic analysis shows a conserved hydrophobic anchorage of the inserti ...201122206988
novel pyridopyrazine and pyrimidothiazine derivatives as ftsz inhibitors.a series of pyridopyrazine and pyrimidothiazine derivatives have been synthesized and their activity against ftsz from mycobacterium tuberculosis (mtb) and in vitro antibacterial activity against mtb h(37)ra and mtb h(37)rv are reported. certain analogs described herein showed moderate to good inhibitory activity.201122024272
[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
Post-laparoscopic wound infection caused by scotochromogenic nontuberculous Mycobacterium.Nontuberculous mycobacteria are known to produce soft-tissue infections following surgical procedures. We report a non-healing surgical wound infection caused by a scotochromogenic nontuberculous mycobacterium, possibly Mycobacterium flavescens, which was earlier thought to be saprophytic. This organism was isolated from the wound discharge at the site of incision following a laparoscopic cholecystectomy; the finding suggests that M. flavescens is a clinically important pathogen in cases of surg ...201121937826
Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis.Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries.201121857806
Stimulation of the Mycobacterium tuberculosis transcription elongation by MtbMfd.The movement of RNA Polymerase (RNAP) along the template during transcription elongation is assisted by a diverse set of proteins with distinct roles. Transcription coupled DNA repair is carried out by Mfd, which dissociates blocked transcription elongation complexes at non-pairing lesions and mediates the repair via recruitment of DNA repair proteins. Mycobacterium tuberculosis Mfd (MtbMfd) influenced the stalled and backtracked RNAP by more than one way. It displaced stalled RNAP blocked by NT ...201122129656
Additional Drug Resistance in Mycobacterium tuberculosis Isolates From Resected Cavities Among Patients With Multidrug-Resistant or Extensively Drug-Resistant Pulmonary Tuberculosis.The pathogenesis of increasing drug resistance among patients with multidrug-resistant or extensively drug-resistant tuberculosis undergoing treatment is poorly understood. Increasing drug resistance found among Mycobacterium tuberculosis recovered from cavitary isolates compared with paired sputum isolates suggests pulmonary cavities may play a role in the development of worsening tuberculosis drug resistance.201122198790
Protection against Mycobacterium tuberculosis challenge in mice by DNA vaccine Ag85A-ESAT-6-IL-21 priming and BCG boosting.Tuberculosis (TB) is one of most important chronic infectious diseases caused by Mycobacterium tuberculosis and remains a major global health problem. In the study, we developed the DNA vaccine encoding fusion protein of antigen 85 A and 6 kDa early secretory antigen target of M. tuberculosis as well as the cytokine IL-21 to investigate its immune protective efficacy against M. tuberculosis challenge in mice after the DNA vaccine priming and Bacille Calmette-Guérin (BCG) boosting. Compared with ...201122152009
mycobacterium doricum osteomyelitis and soft tissue infection. 201122099105
comparison of sterilization of reusable endoscopic biopsy forceps by autoclaving and ethylene oxide gas.every country has standardized reprocessing guidelines for reducing the risk of microorganism transmission via reusable biopsy forceps. sterilization is performed either by autoclaving or with the use of ethylene oxide (eo) gas. however, there are no clear standard global recommendations. the aim of this study was to determine whether eo gas or autoclaving is a safer and more effective method for the sterilization of reusable forceps.201121904859
cardiac tamponade caused by tuberculosis pericarditis in renal transplant recipients.a 50-year-old male, renal transplant recipient, was admitted with fever and chest discomfort. at admission, chest radiologic finding was negative and echocardiography showed minimal pericardial effusion. after 2 days of admission, chest pain worsened and blood pressure fell to 60/40 mmhg. emergency echocardiography showed a large amount of pericardial effusion compressing the entire heart. pericardiocentesis was performed immediately. mycobacterium tuberculosis was isolated from pericardial flui ...201122066081
Clinicopathologic correlation of epidemiologic and histopathologic features of pediatric bacterial lymphadenitis.Infection is a common cause of lymphadenopathy in children and has numerous microbial etiologies. Lymph node biopsy is considered a keystone in arriving at a definite diagnosis. An accurate differential diagnosis from a lymph node biopsy can expedite diagnosis and minimize ancillary testing.201122032579
tuberculosis vaccines: beyond bacille calmette-guerin.tuberculosis (tb) disease caused by mycobacterium tuberculosis (m. tb) remains one of the leading infectious causes of death and disease throughout the world. the only licensed vaccine, mycobacterium bovis bacille calmette-guérin (bcg) confers highly variable protection against pulmonary disease. an effective vaccination regimen would be the most efficient way to control the epidemic. however, bcg does confer consistent and reliable protection against disseminated disease in childhood, and most ...201121893541
Comparison of spoligotyping, mycobacterial interspersed repetitive units typing and IS6110-RFLP in a study of genotypic diversity of Mycobacterium tuberculosis in Delhi, North India.The aim of the present study was to compare polymerase chain reaction (PCR)-based methods--spoligotyping and mycobacterial interspersed repetitive units (MIRU) typing--with the gold-standard IS6110 restriction fragment length polymorphism (RFLP) analysis in 101 isolates of Mycobacterium tuberculosis to determine the genetic diversity of M. tuberculosis clinical isolates from Delhi, North India. Spoligotyping resulted in 49 patterns (14 clusters); the largest cluster was composed of Spoligotype I ...201121894371
Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis.The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites tha ...201121962569
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
Infectious diseases biobanking as a catalyst towards personalized medicine: Mycobacterium tuberculosis paradigm.Research for biomarkers supporting personalized medicine in infectious diseases is needed, especially for tuberculosis in which the existing toolbox does not yet address the public health priorities. Biobanks are essential infrastructures in this effort by collecting, authenticating and preserving human and/or bacterial specimens. A broad range of specimens should be collected prior to, during and following treatment, with a comprehensive characterisation of the sample donors and the samples the ...201121855413
The ß-propeller gene Rv1057 of Mycobacterium tuberculosis has a complex promoter directly regulated by both the MprAB and TrcRS two-component systems.The ß-propeller gene Rv1057 of Mycobacterium tuberculosis is activated by envelope stress and was first characterized as a regulatory target of the TrcRS two-component system (TCS). Rv1057 expression is repressed by TrcRS, and the Rv1057 proximal promoter contains a TrcR binding site. In this study, we determined that Rv1057 is also directly regulated by MprAB, a TCS associated with envelope stress. Multiple potential MprA binding sites (MprA boxes) were identified in the 1 kb intergenic region ...201122099420
tuberculosis patients are characterized by a low-ifn-γ/high-tnf-α response to methylated hbha produced in m. smegmatis.whole blood from mycobacterium tuberculosis-infected subjects was stimulated with heparin-binding hemagglutinin (hbha). tuberculosis (tb) patients showed an hbha-specific t-cell response characterized by low-ifn-γ/high-tnf-α secretion, while asymptomatic subjects with latent infection (ltbi) and tb patients under therapy showed a pattern with high ifn-γ/low tnf-α. these results underscore the usefulness of hbha in helping to distinguish ltbi subjects versus tb patients.201122083081
Design, Synthesis, and Evaluation of Thiol-Activated Sources of Sulfur Dioxide (SO(2)) as Antimycobacterial Agents.Here, 2,4-dinitrophenylsulfonamides with tunable cysteine-activated SO(2) release profiles with half-lives of SO(2) release varying from 2 to 63 min are reported. N-Benzyl-2,4-dinitrobenzenesulfonamide (6), which is prepared in one step from commercial sources, had a potency (MIC = 0.15 µM) of inhibiting Mycobacterium tuberculosis (Mtb) higher than the clinical agent isoniazid (MIC = 0.37 µM).201122128803
Ovine paratuberculosis: a seroprevalence study in dairy flocks reared in the marche region, Italy.In order to fulfil the seroprevalence gap on Mycobacterium avium subsp. paratuberculosis infection in ovine dairy farms of Marche region (central Italy), a stratified study was carried out on 2086 adult female sheep randomly chosen from 38 herds selected in Ancona and Macerata provinces. 73.7% flocks resulted infected by a commercial ELISA test (Pourquier, France), with a mean seroprevalence of 6.29% of sampled sheep in both provinces. A higher number of MAP seropositive ewes was recorded in the ...201121876850
Mycobacterium ulcerans Infection (Buruli Ulcer) on the Face: A Comparative Analysis of 13 Clinically Suspected Cases from the Democratic Republic of Congo.Abstract. We report our experience in managing 13 consecutive clinically suspected cases of Buruli ulcer on the face treated at the hospital of the Institut Médical Evangélique at Kimpese, Democratic Republic of Congo diagnosed during 2003-2007. During specific antibiotherapy, facial edema diminished, thus minimizing the subsequent extent of surgery and severe disfigurations. The following complications were observed: 1) lagophthalmos from scarring in four patients and associated ectropion in th ...201122144452
Usefulness of three-channel multiplex real-time PCR and melting curve analysis for simultaneous detection and identification of the Mycobacterium tuberculosis complex and nontuberculous mycobacteria.We attempted to determine the benefits of three-channel multiplex real-time PCR and melting curve analysis not only in detecting and distinguishing between nontuberculous mycobacteria (NTM) and the Mycobacterium tuberculosis complex but also in identifying NTM to the species level.201121918032
functional analysis of dna replication fork reversal catalyzed by mycobacterium tuberculosis ruvab proteins.initially discovered in escherichia coli, ruvab proteins are ubiquitous in bacteria and play a dual role as molecular motor proteins responsible for branch migration of the holliday junction(s) and reversal of stalled replication forks. despite mounting genetic evidence for a crucial role of ruva and ruvb proteins in reversal of stalled replication forks, the mechanistic aspects of this process are still not fully understood. here, we elucidate the ability of mycobacterium tuberculosis ruvab (mt ...201122094465
Drug susceptibility pattern of Mycobacterium tuberculosis isolates against conventional anti-tuberculosis drugs in Dhaka, Bangladesh. 201122159394
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
british hiv association national audit on the management of patients co-infected with tuberculosis and hiv.this audit aims to compare uk management of tuberculosis (tb)/hiv co-infection with recommended practice and to describe local care arrangements. services providing hiv care were invited to complete a survey of care arrangements and to review case notes of hiv positive patients aged over 16 who started therapy for active tb between october 2007 and april 2008. corresponding tb services, if separate, were invited to complete a similar survey. responses were received from 124 of 170 hiv services, ...201121902071
Computational Analysis of the ESX-1 Region of Mycobacterium tuberculosis: Insights into the Mechanism of Type VII Secretion System.Type VII secretion system (T7SS) is a recent discovery in bacterial secretion systems. First identified in Mycobacterium tuberculosis, this secretion system has later been reported in organisms belonging to the Actinomycetales order and even to distant phyla like Firmicutes. The genome of M. tuberculosis H37Rv contains five gene clusters that have evolved through gene duplication events and include components of the T7SS secretion machinery. These clusters are called ESAT-6 secretion system (ESX ...201122140496
Neonatal tuberculosis: neonatal intensive care unit considerations in the United States.According to the World Health Organization, more than 2 billion people, equal to one third of the world's population, are infected with Mycobacterium tuberculosis (TB) bacilli, the microbes that cause TB. In addition, over the past decade, the incidence of postnatal TB in infants has shown an escalating trend in response to the global increase in TB. In providing the best possible care for infants in newborn nurseries and NICU, providers must recognize the trends of TB and multidrug resistant TB ...201121926897
[Evaluation of GenoType MTBDRplus for the detection of multi-drug-resistant Mycobacterium tuberculosis strains].To evaluate GenoType MTBDRplus (Hain Lifescience, Germany) for its capacity to detect the resistance of rifampicin (RFP) and isoniazid (INH).201121922778
the evidence of large-scale dna-induced compaction in the mycobacterial chromosomal parb.the bacterial chromosome trafficking apparatus or the segrosome participates in the mitotic-like segregation of the chromosomes prior to cell division in several bacteria. parb, which is the pars dna-binding component of the segrosome, polymerizes on the pars-adjacent chromosome to form a nucleoprotein filament of unknown nature for the segregation function. we combined static light scattering, circular dichroism and small-angle x-ray scattering to present evidence that the apo form of the mycob ...201121839743
understanding the interaction of lipoarabinomannan with membrane mimetic architectures.lipoarabinomannan (lam) is a critical virulence factor in the pathogenesis of mycobacterium tuberculosis, the causative agent of tuberculosis. lam is secreted in urine and serum from infected patients and is being studied as a potential diagnostic indicator for the disease. herein, we present a novel ultra-sensitive and specific detection strategy for monomeric lam based on its amphiphilic nature and consequent interaction with supported lipid bilayers. our strategy involves the capture of lam o ...201122033469
concomitant administration of mycobacterium bovis bcg with the meningococcal c conjugate vaccine to neonatal mice enhances antibody response and protective efficacy.mycobacterium bovis bcg is administered to human neonates in many countries worldwide. the objective of the study was to assess if bcg could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. we assessed whether bcg could enhance immune responses to a meningococcal c (menc) conjugate vaccine, menc-crm(197), in mice primed as neonates, broaden the antibody r ...201121900528
evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.in sub-saharan africa, hiv-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, mycobacterium tuberculosis and malaria parasites. the consequences are often devastating, resulting in enhanced morbidity and mortality. due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (siv)-malaria coinfection. in sub-saharan africa, plasmodium falcipa ...201121917966
nineteen cases of buruli ulcer diagnosed in japan from 1980 to 2010.the etiology, clinical manifestations, and treatment of 19 sporadic cases of buruli ulcer (bu) in japan are described. the cases originated in different regions of honshu island, with no evidence of patient contact with an aquatic environment. the majority (73.7%) of cases occurred in females, with an average age of 39.1 years for females and 56.8 years for males. all patients developed ulcers on exposed areas of the skin (e.g., face, extremities). most ulcers were <5 cm in diameter (category i) ...201121880966
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
diagnostic performance of enzyme-linked immunospot assay and whole-blood interferon-γ assay for the diagnosis of extrapulmonary tuberculosis. 201121855430
[Structurally-functional status of heart of the tuberculosis in teenagers].The patients divided into two groups: in 12 patients (13-16 years old) including into I group observed decrease of internal size of the left ventricle, in 8 persons (17-18 year old) revealed the elevation of internal size of the cavity of the left ventricle. From the analysis of results of the observations it is seen that, in patients including into 1 group the thickness of the wall of the left ventricle is higher than the internal size of the ventricular cavity. This time, the main aim of hyper ...201121954637
Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation.During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5--two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators--during the macrophage infection cycle. Using wild-type, ESX-1- an ...201121957139
[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
validation of pnca gene sequencing in combination with the mycobacterial growth indicator tube method to test susceptibility of mycobacterium tuberculosis to pyrazinamide.pyrazinamide is important in the treatment of tuberculosis. unfortunately, the diagnosis of pyrazinamide resistance is hampered by technical difficulties. we hypothesized that mutation analysis combined with the mycobacterial growth indicator tube (mgit) phenotypic method would be a good predictor of pyrazinamide resistance. we prospectively analyzed 1,650 m. tuberculosis isolates referred to our tuberculosis reference laboratory in 2008 and 2009. in our laboratory, the mgit 960 system was used ...201122090409
delivery of a multivalent scrambled antigen vaccine induces broad spectrum immunity and protection against tuberculosis.the development of effective anti-tuberculosis (tb) vaccines is an important step towards improved control of tb in high burden countries. subunit vaccines are advantageous in terms of safety, particularly in the context of high rates of hiv co-infection, but they must contain sufficient mycobacterium tuberculosis antigens to stimulate immunity in genetically diverse human populations. we have used a novel approach to develop a synthetic scrambled antigen vaccine (tb-savine), comprised of overla ...201121846485
Identification of Mycobacterium bovis among mycobacterial isolates from human clinical specimens at a university hospital in Rio de Janeiro, Brazil.In 2005 and 2006, 8,121 clinical specimens submitted to the Mycobacteriology Laboratory of the Clementino Fraga Filho University Hospital/Thoracic Diseases Institute, in the city of Rio de Janeiro, Brazil, were inoculated on Löwenstein-Jensen medium containing glycerol and pyruvate. There were 79 mycobacteria isolates that presented growth only on pyruvate-containing medium, and those isolates were selected for the presumptive identification of Mycobacterium bovis. The selected isolates were scr ...201122042400
Investigation of ABC transporter from mycobacterial arabinogalactan biosynthetic cluster.Two genes from the "mycobacterial arabinogalactan biosynthetic cluster" spanning the region from Rv3779 to Rv3809c in the genome of Mycobacterium tuberculosis H37Rv were annotated as possible components of the ATP-binding cassette transporter. Rv3781 encodes a nucleotide-binding domain and Rv3783 determines production of a membrane-spanning domain. We have examined possible roles of these genes in mycobacterial cell wall biosynthesis through inactivation of their respective orthologs in Mycobact ...201121952433
diagnosis of tuberculosis by trained african giant pouched rats and confounding impact of pathogens and microflora of the respiratory tract.trained african giant-pouched rats (cricetomys gambianus) can detect mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis (tb). however, rats' ability to discriminate between clinical sputum containing other mycobacterium spp. and nonmycobacterial species of the respiratory tract is unknown. it is also unknown whether nonmycobacterial species produce odor similar to m. tuberculosis and thereby cause the detection of smear-negative sputum. sputum samples from 289 subjec ...201122135255
evaluation of tuberculosis diagnostics: establishing an evidence base around the public health impact.the limitations of existing tuberculosis diagnostic tools are significantly hampering tuberculosis control efforts, most noticeably in areas with high prevalence of human immunodeficiency virus (hiv) infection and antituberculosis drug resistance. however, renewed global interest in tuberculosis research has begun to bear fruit, with several new diagnostic technologies progressing through the development pipeline. there are significant challenges in building a sound evidence base to inform publi ...201121996701
Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbia ...201121953458
nonspecific interaction between dna and protein allows for cooperativity: a case study with mycobacterium dna binding protein.different dna-binding proteins have different interaction modes with dna. sequence-specific dna-protein interaction has been mostly associated with regulatory processes inside a cell, and as such extensive studies have been made. adequate data is also available on nonspecific dna-protein interaction, as an intermediate to protein's search for its cognate partner. multidomain nonspecific dna-protein interaction involving physical sequestering of dna has often been implicated to regulate gene expr ...201122091866
Multiple skin lesions caused by Mycobacterium scrofulaceum infection. 201121982841
mycobacterium phlei, a previously unreported cause of pacemaker infection: thinking outside the box in cardiac device infections.the increased use of cardiac rhythm management devices has led to an increase in cardiac device-related infections (cdi). staphylococcus aureus and epidermidis account for the vast majority of cdi. cdi due to rapidly growing non-tuberculous mycobacteria is very rare, with only about ten cases having been reported. we report a case of pacemaker pocket infection with mycobacterium phlei. there are only three published reports of human infection involving this typically non-pathogenic organism. to ...201122113758
a rare case of infectious colitis with ulcers in the cecum caused by mycobacterium gordonae.a 69-year-old female complained of persistent abdominal pain, and annular ulcers and ulcer scars were detected endoscopically in the cecum. pathological findings included caseous granulomas with some langhans giant cells, and ziehl-neelsen staining was negative. mycobacterium gordonae (m. gordonae) was identified by the dna-dna hybridization method and culture (ogawa medium) of biopsy samples from ulcerous cecal lesions. after 6 months of antibiotic therapy, ulcerous cecal lesions were healed, a ...201122041361
New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity.Four new flavanones, cryptoflavanones A-D (1-4, resp.), together with eight known compounds, were isolated from the leaves of Cryptocarya chinensis. The structures of these new compounds were determined by spectral analyses. Among the isolated compounds, pinocembrin (5) and cryptocaryone (6) exhibited antituberculosis activity against Mycobacterium tuberculosis H(37) Rv strain in vitro with MIC values of 3.5 and 25.0 µg/ml, respectively.201122083914
Genetic susceptibility to paratuberculosis.Multiple studies indicate that host animal genetics play a role in susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection. However, due to differences in methods used to define MAP-infected animals and controls and differences in methods of genetic analysis, there is as yet no clear consensus on the genes or markers to reliably define the MAP infection susceptibility of any animal species. Meta-analysis of combined studies and larger studies will help resolve the situation ...201122023834
Changes in the size and number of skin lesions in PB leprosy on treatment and follow-up.The increase in size of existing skin lesions and appearance of new skin lesions are considered important signs of clinical activity both in untreated and treated leprosy. To confirm such activity, the number and size of lesions need to be recorded methodically prior to therapy and on follow-up, especially in PB leprosy where clinical signs alone define the reactivation of the disease. However, no systematic follow-up studies are available on changes in size and number of skin lesions in PB lepr ...201122125932
Structural analyses of a purine biosynthetic enzyme from Mycobacterium tuberculosis reveal a novel bound nucleotide.Enzymes of the de novo purine biosynthetic pathway have been identified as essential for the growth and survival of Mycobacterium tuberculosis and thus have potential for the development of anti-tuberculosis drugs. The final two steps of this pathway are carried out by the bifunctional enzyme 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase (ATIC), also known as PurH. This enzyme has already been the target of anti-cancer drug development. We have ...201121956117
Detection of Mycobacterium abscessus from blood cultures during treatment of interstitial pneumonia: a case study.A 76-year-old male diagnosed with interstitial pneumonia in December 2002 was treated with a steroid in a nearby hospital. Exacerbation of infectious pneumonitis and interstitial pneumonia required complementary inpatient treatment in August 2007. Although polymerase chain reaction examination of expectorated sputa revealed the absence of Mycobacterium tuberculosis, M. avium, and M. intracellulare on admission, nontuberculous M. abscessus was detected in the routine blood cultures. Taken togethe ...201122111302
tuberculosis in antiretroviral treatment services in resource-limited settings: addressing the challenges of screening and diagnosis.the high burden of tuberculosis (tb) among patients accessing antiretroviral treatment (art) services in resource-limited settings is a major cause of morbidity and mortality and is associated with nosocomial transmission risk. these risks are greatly compounded by multidrug-resistant disease. screening and diagnosis of tb in this clinical setting is difficult. however, progress has been made in defining a high-sensitivity, standardized symptom screening tool that assesses a combination of sympt ...201121996698
phosphorylation of phop protein plays direct regulatory role in lipid biosynthesis of mycobacterium tuberculosis.mycobacterium tuberculosis phop is essential for virulence and intracellular growth of the tubercle bacilli. genetic evidence suggests that phop regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phop mutant partly accounts for its attenuated growth in macrophages and/or mice. to investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of phop in the regulation of complex lipid biosynthesis. we show that phosphorylated ...201122072719
dna fingerprinting of mycobacterium tuberculosis: from phage typing to whole-genome sequencing.current typing methods for mycobacterium tuberculosis complex evolved from simple phenotypic approaches like phage typing and drug susceptibility profiling to dna-based strain typing methods, such as is6110-restriction fragment length polymorphisms (rflp) and variable number of tandem repeats (vntr) typing. examples of the usefulness of molecular typing are source case finding and epidemiological linkage of tuberculosis (tb) cases, international transmission of mdr/xdr-tb, the discrimination bet ...201122067515
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
Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies.ABSTRACT:201122111760
Antimycobacterial activity of steroids, long-chain alcohols and lytic peptides.As a continuation of our project aimed at a search for new antimycobacterial agents, several naturally occurring and synthetic compounds have been evaluated against Mycobacterium tuberculosis H37Rv and M. avium. Emphasis was placed on steroids and a series of isoprene long-chain alcohols to gain new insight into their structural activities. Maximum activity of isoprenoid derivatives seemed to depend on the hydrophobic chain length from the hydrophilic hydroxyl moiety. In contrast, ergosterol per ...201121851148
Multidrug resistance after inappropriate tuberculosis treatment: A meta-analysis.We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug resistant tuberculosis (MDR-TB).MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients that received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or ...201122005918
Generation and Analysis of Large-Scale Data-Driven Mycobacterium tuberculosis Functional Networks for Drug Target Identification.Technological developments in large-scale biological experiments, coupled with bioinformatics tools, have opened the doors to computational approaches for the global analysis of whole genomes. This has provided the opportunity to look at genes within their context in the cell. The integration of vast amounts of data generated by these technologies provides a strategy for identifying potential drug targets within microbial pathogens, the causative agents of infectious diseases. As proteins are dr ...201122190924
Mouse Model of Necrotic Tuberculosis Granulomas Develops Hypoxic Lesions.Background. Preclinical evaluation of tuberculosis drugs is generally limited to mice. However, necrosis and hypoxia, key features of human tuberculosis lesions, are lacking in conventional mouse strains.Methods. We used C3HeB/FeJ mice, which develop necrotic lesions in response to Mycobacterium tuberculosis infection. Positron emission tomography in live infected animals, postmortem pimonidazole immunohistochemistry, and bacterial gene expression analyses were used to assess whether tuberculosi ...201122198962
Evaluation of VersaTREK Compared to BACTEC MGIT960 Systems for First Line Drug Susceptibility Testing Of Mycobacterium tuberculosis.The aim of this study was to evaluate the reliability of VersaTREK System in M.tuberculosis drug susceptibility testing compared with BACTEC MGIT960. A total of 67 strains were evaluated. Overall agreement was of 98.5%. Kappa indexes were: 1.0 for isoniazid, rifampin and ethambutol, 0.937 for pyrazinamide and 0.907 for streptomycin. The VersaTREK is validated for M.tuberculosis drug susceptibility testing.201122135258
Mining Genomic Patterns in Mycobacterium tuberculosis H37Rv Using a Web Server Tuber-Gene.Mycobacterium tuberculosis (MTB), causative agent of tuberculosis, is one of the most dreaded diseases of the century. It has long been studied by researchers throughout the world using various wet-lab and dry-lab techniques. In this study, we focus on mining useful patterns at genomic level that can be applied for in silico functional characterization of genes from the MTB complex. The model developed on the basis of the patterns found in this study can correctly identify 99.77% of the input ge ...201122196360
the role of the novel exopolyphosphatase mt0516 in mycobacterium tuberculosis drug tolerance and persistence.inorganic polyphosphate (poly p) has been postulated to play a regulatory role in the transition to bacterial persistence. in bacteria, poly p balance in the cell is maintained by the hydrolysis activity of the exopolyphosphatase ppx. however, the mycobacterium tuberculosis ppx has not been characterized previously. here we show that recombinant mt0516 hydrolyzes poly p, and an mt0516-deficient m. tuberculosis mutant exhibits elevated intracellular levels of poly p and increased expression of th ...201122132215
Longevity of Mycobacterium bovis in brushtail possum (Trichosurus vulpecula) carcasses, and contact rates between possums and carcasses.To determine, for a variety of environmental conditions, how long Mycobacterium bovis might remain viable inside the carcass of a brushtail possum (Trichosurus vulpecula) that died of bovine tuberculosis (Tb), and to measure the rate of contact between free-ranging possums and possum carcasses.201121851297
real-time pcr in infectious uveitis as an alternative diagnosis.uveitis is a major visual impairment disease affecting parts or the entire uveal tract and occasionally the sclera, the cornea or the optic nerve. the disease is a major cause of ocular morbidity and blindness in immunocompetent and immunocompromised patients. in this work we analyzed the sensitivity and specificity of real-time pcr to detect the etiological agent from blood, plasma, vitreous and aqueous humor and compared with the diagnostic hypothesis.201122068852
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
peritoneal dialysis-associated nontuberculous mycobacterium peritonitis: a systematic review of reported cases.background: peritonitis caused by nontuberculous mycobacterium (ntm) is an important complication in peritoneal dialysis (pd) patients.methods: cases of pd complicated by ntm peritonitis reported in the english language literature were identified in the pubmed database. the characteristics of these cases were reviewed.results: in 41 articles, we identified 57 cases of pd-associated ntm peritonitis in patients ranging from 5 to 82 years. the prevalent clinical findings of these cases were fever, ...201121891775
pknE, a serine/threonine kinase of Mycobacterium tuberculosis modulates multiple apoptotic paradigms.Mycobacterium tuberculosis, an intracellular pathogen that causes tuberculosis has developed multifactorial mechanisms to evade host signaling responses. Apoptosis, an important innate host immune response that clears the invading pathogen is suppressed by M. tuberculosis to gain persistence. Here, we examined the various apoptotic events suppressed by Protein Kinase E, (pknE) a Serine Threonine Protein Kinase (STPK) of M. tuberculosis in macrophages infected with ?pknE, a deletion mutant of pkn ...201121945589
case records of the massachusetts general hospital. case 27-2011. a 17-year-old boy with abdominal pain and weight loss. 201121899455
Mass Spectrometric Analysis of Mycothiol levels in Wild-Type and Mycothiol Disulfide Reductase Mutant Mycobacterium smegmatis.Mycothiol (MSH), the primary low-molecular weight thiol produced in mycobacteria, acts to protect the cell from oxidative stress and to maintain redox homeostasis, notably in the pathogenic Mycobacterium tuberculosis in the course of human infection. The mycothiol disulfide reductase (Mtr) enzyme reduces the oxidized form of mycothiol, mycothione (MSSM), back to MSH, however its role in bacterial viability is not clear. In this study, we sought to determine the MSH levels of wild-type (WT) and M ...201121857792
a ring-closing metathesis (rcm)-based approach to mycolactones a/b.the total synthesis of the mycobacterial toxins mycolactones a/b (1 a/b) has been accomplished based on a strategy built around the construction of the mycolactone core through ring-closing metathesis. by employing the grubbs second-generation catalyst, the 12-membered core macrocycle of mycolactones, with a functionalized c2 handle attached to c11, was obtained in 60-80 % yield. the c-linked upper side chain (comprising c12-c20) was completed by a highly efficient modified suzuki coupling betwe ...201121971832
Communicable diseases prioritized for surveillance and epidemiological research: results of a standardized prioritization procedure in Germany, 2011.To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research.201121991334
outbreak of mycobacterium avium subsp. avium infection in one flock of domestic pigeons.an outbreak of mycobacterium avium subsp. avium infection was diagnosed in one breed of domestic pigeons (columba livia f. domestica) in the czech republic. nodular granulomatous lesions were found in 42 (9.7%) pigeons of the 435 examined; histopathologic examination of livers with gross lesions of mycobacteriosis from 15 randomly selected pigeons revealed granulomatous inflammation typical for avian mycobacteriosis in all samples. direct ziehl-neelsen (zn) microscopy and conventional culture we ...201122017056
Incidence of isolation of mycobacterium tuberculosis from blood samples in tuberculosis patients in Imam Khomeini Hospital, Tehran, Iran.It is estimated that one third of the world's population is latently infected with tuberculosis (TB). The HIV epidemic fuels the TB epidemic by increasing the risk of reactivation of latent TB infection and by facilitating a more rapid progression of TB disease. Although the incidence of TB is constant or decreasing in many regions of the world, rates remain high in developing countries as a consequence of the HIV epidemic. This study was conducted as a collaboration of the Infectious Diseases d ...201122009814
rv2607 from mycobacterium tuberculosis is a pyridoxine 5'-phosphate oxidase with unusual substrate specificity.despite intensive effort, the majority of the annotated mycobacterium tuberculosis genome consists of genes encoding proteins of unknown or poorly understood function. for example, there are seven conserved hypothetical proteins annotated as homologs of pyridoxine 5'-phosphate oxidase (pnpox), an enzyme that oxidizes pyridoxine 5'-phosphate (pnp) or pyridoxamine 5'-phosphate (pmp) to form pyridoxal 5'-phosphate (plp). we have characterized the function of rv2607 from mycobacterium tuberculosis h ...201122110704
understanding the biology of 16 kda antigen of mycobacterium tuberculosis: scope in diagnosis, vaccine design and therapy.heat shock proteins (hsps) are conserved and ubiquitous house keeping entities that act as molecular chaperones, which protect the cell from damage during stress. one such hsp, the 16 kda antigen, from mycobacterium tuberculosis (mtb) has received considerable attention due to its importance in tuberculosis latency and immunodominant property. in this article, we discuss about the potential role of 16 kda antigen of mtb in latency, its expression, regulation, and implication in host immune respo ...201121919701
Epitope based recombinant BCG vaccine elicits specific Th1 polarized immune responses in BALB/c mice.Developing an efficacious vaccine is one of the highest priorities in tuberculosis research. A vaccine based on T cell epitopes representing multiple antigens is an ideal approach to generate effective cellular immunity against the disease. In the present study, we have selected four T cell epitopes from four well defined Mycobacterium tuberculosis antigens, Ag85C (Rv2903c), 10-kDa culture filtrate protein (CFP-10) (Rv3874), PPE68 (Rv3873) and INV 2 (Rv1478). The epitope encoding genes were graf ...201122200502
Absence of Mycobacterium bovis in feral swine (Sus scrofa) from the southern Texas border region.Free-ranging wildlife, such as feral swine (Sus scrofa), harbor a variety of diseases that are transmissible to livestock and could negatively impact agricultural production. Information is needed regarding the exposure and infection rates of Mycobacterium bovis and many other diseases and parasites in feral swine occurring in the Texas border region. Our main objective was to determine exposure rates and possible infection rates of M. bovis in feral swine by opportunistically sampling animals f ...201122102669
Mycobacterium tuberculosis: an infection we should suspect in bone marrow transplantation. 201122005068
Web tools for molecular epidemiology of tuberculosis.In this study we explore publicly available web tools designed to use molecular epidemiological data to extract information that can be employed for the effective tracking and control of tuberculosis (TB). The application of molecular methods for the epidemiology of TB complement traditional approaches used in public health. DNA fingerprinting methods are now routinely employed in TB surveillance programs and are primarily used to detect recent transmissions and in outbreak investigations. Here ...201121903179
outbreaks of mycobacterium tuberculosis mdr strains induce high il-17 t-cell response in patients with mdr tuberculosis that is closely associated with high antigen load.the proinflammatory cytokine interleukin 17 (il-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. so, we evaluated the ability of mycobacterium tuberculosis clinical isolates to induce il-17 in tuberculosis (tb) patients and in healthy human tuberculin reactors (ppd(+)hd).201121881121
control of paratuberculosis in beef cattle.as with any susceptible livestock species, the key to control of paratuberculosis in beef cattle is to reduce exposure of the susceptible calves to mycobacterium avium subsp. paratuberculosis (map)–contaminated feces. because beef calves remain with mature, potentially shedding cattle until weaning, control strategies are aimed at providing an environment with the least possible fecal burden and removing map shedders as soon as possible. testing and culling or separation may be more important in ...201122023837
Efficacy and safety of once-daily nevirapine- or efavirenz-based antiretroviral therapy in HIV-associated tuberculosis: a randomized clinical trial.Nevirapine (NVP) can be safely and effectively administered once-daily but has not been assessed in human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB). We studied the safety and efficacy of once-daily NVP, compared with efavirenz (EFV; standard therapy); both drugs were administered in combination with 2 nucleoside reverse-transcriptase inhibitors.201121890776
Characteristics of multidrug-resistant Mycobacterium tuberculosis in southern Brazil.A major threat to tuberculosis (TB) control programs is the emergence of drug resistant Mycobacterium tuberculosis strains that cause TB that cannot be cured by standard anti-TB drug regimens. Because few data exist on MDR-TB in this region of the country, we performed an epidemiologic study that combined conventional and molecular analysis of MDR-TB cases from Rio Grande do Sul (RS) that were diagnosed in this period and included cases that were under treatment with second line drug schemes. In ...201122001593
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