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reduced turn-around time for mycobacterium tuberculosis drug susceptibility testing with a proportional agar microplate assay.multidrug-resistant tuberculosis is a major issue worldwide; however, accessibility to drug susceptibility testing (dst) is still limited in developing countries, owing to high costs and complexity. we developed a proportion method on 12-well microplates for dst. the assay reduced the time to results to <12 days and <10 days when bacterial growth was checked with the naked eye or a microscope, respectively. comparison with the canetti-grosset method showed that the results of the two assays almo ...201526348263
acquisition of second-line drug resistance and extensive drug resistance during recent transmission of mycobacterium tuberculosis in rural china.multidrug-resistant tuberculosis (mdr-tb) is prevalent in countries with a high tb burden, like china. as little is known about the emergence and spread of second-line drug (sld) -resistant tb, we investigate the emergence and transmission of sld-resistant mycobacterium tuberculosis in rural china. in a multi-centre population-based study, we described the bacterial population structure and the transmission characteristics of sld-resistant tb using spoligotyping in combination with genotyping ba ...201526348262
exposure of monocytes to lipoarabinomannan promotes their differentiation into functionally and phenotypically immature macrophages.lipoarabinomannan (lam) is a lipid virulence factor secreted by mycobacterium tuberculosis (mtb), the etiologic agent of tuberculosis. lam can be measured in the urine or serum of tuberculosis patients (tb-patients). circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to lam in patients with active tb. we speculated that exposing monocytes to lam could produce phenotypically and functionally immature macrophages. to test our hypothesis, human monocytes were ...201526347897
a subgroup of latently mycobacterium tuberculosis infected individuals is characterized by consistently elevated iga responses to several mycobacterial antigens.elevated antibody responses to mycobacterium tuberculosis antigens in individuals with latent infection (ltbi) have previously been linked to an increased risk for progression to active disease. studies in the field focussed mainly on igg antibodies. in the present study, iga and/or igg responses to the mycobacterial protein antigens aladh, narl, 19 kda, psts3, and mpt83 were determined in a blinded fashion in sera from 53 ltbi controls, 14 healthy controls, and 42 active tb subjects. among cont ...201526347586
interactome analysis and design of inhibitors against selected protein targets of ser/thr protein kinase (stpk) signaling pathways in mycobacterium tuberculosis h37rv.tuberculosis continues to be a major cause of mortality worldwide despite significant advances in chemotherapy and development of the bcg vaccine. although curable, the tuberculosis treatment period (6-9 months) presents many concerns, including patient noncompliance and the development of drug toxicity and drug resistance. this study aimed to understand the protein-protein interactions of key proteins involved in the mycobacterium tuberculosis stpk signal transduction pathway (such as pknb, pkn ...201526345980
mycobacterium tuberculosis. 201526345333
tuberculine reaction measured by infrared thermography.the infection with mycobacterium tuberculosis gives a delayed immune response, measured by the tuberculine skin test. we present a new technique for evaluation based on automatic detection and measurement of skin temperature due to infrared emission.201526344585
the association between sterilizing activity and drug distribution into tuberculosis lesions.finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (tb) drug development. using a matrix-assisted laser desorption/ionization (maldi) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of tb infection in lung lesions. rifampicin even accumulates in necrotic caseum, a critical ...201526343800
isoniazid@fe2 o3 nanocontainers and their antibacterial effect on tuberculosis mycobacteria.isoniazid-filled fe2 o3 hollow nanospheres (inh@fe2 o3 , diameter <30 nm, 48 wt % inh-load) are prepared for the first time and suggested for tuberculosis therapy. after dextran-functionalization, the inh@fe2 o3 @dex nanocontainers show strong activity against mycobacterium tuberculosis (m.tb.) and m.tb.-infected macrophages. the nanocontainers can be considered as "trojan horses" and show efficient, active uptake into both m.tb.-infected macrophages and even into mycobacterial cells.201526332072
comparison of roentgenographic manifestations of active pulmonary tuberculosis between migrant and non-migrant populations in the hunter region.active pulmonary tuberculosis in australia is considered more common in migrants and the immunocompromised, but little data exist on how it manifests in non-migrants. this study identified the radiographic findings of active pulmonary tuberculosis in the hunter region, nsw, australia, and determined whether this manifests differently in non-migrant and migrant populations.201526331375
implant-associated mycobacterium tuberculosis infection following surgical management of fractures: a retrospective observational study.in this retrospective observational cohort study, we describe 17 patients out of 1775 treated for various fractures who developed mycobacterium tuberculosis (mtb) infection after surgery. the cohort comprised 15 men and two women with a mean age of 40 years (24 to 70). a total of ten fractures were open and seven were closed. of these, seven patients underwent intramedullary nailing of a fracture of the long bone, seven had fractures fixed with plates, two with kirschner-wires and screws, and on ...201526330597
comparative study of adenosine deaminase and other conventional diagnostic parameters in diagnosis of tuberculous pleural effusion.though pulmonary tuberculosis is the common presentation of mycobacterium tuberculosis infection, extra-pulmonary tuberculosis is also a growing problem worldwide. tuberculous pleural effusion is the second frequent form of extra-pulmonary presentation after tuberculous lymphadenitis and if untreated up to 65% of patients with tubercular pleural effusions will eventually develop active tb. traditional diagnostic methods are very useful for the diagnosis of pulmonary tb but have a low yield when ...201526329954
[acquired bronchial atresia due to endobronchial tuberculosis].a 37-year-old woman was re-admitted to our hospital because the recurrence of endobronchial tuberclosis was suspected. mycobacterium tuberculosis was not detected by culture of sputum and gastric fluid, and computed tomography revealed a left superior segmental bronchus obstruction and pneumonia. her pneumonia improved by administration of antibiotics, but the strong cough persisted. bronchoscopic examination revealed that the left superior segmental bronchus was blind. mycobacterium tuberculosi ...201526329627
multidrug-resistant mycobacterium tuberculosis and associated risk factors in oromia region of ethiopia.the aim of this study was to determine risk factors for tuberculosis (tb) caused by multidrug-resistant mycobacterium tuberculosis (mdr-tb) in oromia region, ethiopia.201526327121
mycobacterium tuberculosis complex transmission is not associated with recent immigration (≤5 years) in florida.as tuberculosis (tb) incidence decreases in the us, foreign-born persons continue to account for a larger proportion of the burden. in these cross-sectional analyses of 1149 culture-confirmed tb cases genotyped using spoligotyping and 24-locus miru, we show that over a quarter of cases among the foreign-born population in florida resulted from recent transmission of the mycobacterium tuberculosis complex. in addition, over a third of these cases occurred among persons who had immigrated 5 years ...201526325684
evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of mycobacterium tuberculosis from iran.absence of mutations within the genes encoding drug targets in some phenotypically drug resistant strains of mycobacterium tuberculosis suggests possible involvement of alternative mechanisms such as over-expression of efflux pumps. we investigated the expression level of rv1410c, rv2459, rv1218c and rv1273c efflux pumps gene by real-time quantitative reverse transcription pcr (qrt-pcr) in 31 clinical isolates of m. tuberculosis. susceptibility to first-line drugs was performed using the proport ...201526325681
exogenous reinfection as a cause of late recurrent tuberculosis in the united states.the etiology of recurrent tuberculosis is typically presumed to be reactivation of residual mycobacterium tuberculosis infection, but reinfection may account for a greater proportion of recurrent tuberculosis than previously recognized.201526325356
microrna signatures from multidrug‑resistant mycobacterium tuberculosis.tuberculosis (tb) infections, caused by multidrug‑resistant mycobacterium tuberculosis (mdr mtb), remain a significant public health concern worldwide. the regulatory mechanisms underlying the emergence of mdr mtb strains remain to be fully elucidated, and further investigation is required in order to develop better strategies for tb control. the present study investigated the expression profile of microrna (mirna) in mtb strains, and examined the differences between sensitive mtb and mdr mtb us ...201526324150
mir-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting foxo3.the aim of the present study was to investigate the association between microrna (mir)-155 and apoptosis of monocytes infected by mycobacterium tuberculosis, to examine the effect of forkhead box o3 (foxo3) on mir‑155. the present study analysed the apoptosis of cd14+ in the peripheral blood of patients with active tuberculosis, disposed the thp‑1 human monocytic cell line by bcg and examined the expression of mir‑155. furthermore, the expression of foxo3 in thp‑1 cells was determined, and wild- ...201526324048
computational evaluation of phytocompounds for combating drug resistant tuberculosis by multi-targeted therapy.the cell wall of mycobacterium tuberculosis interacts with the host counterpart during the pathogenesis of tuberculosis. l-rhamnosyl (l-rha) residue, a linker connects the arabinogalactan and peptidoglycan moieties in the bacterial cell wall. the biosynthesis of l-rhamnose utilizes four successive enzymes rmla, rmlb, rmlc and rmld. neither rhamnose nor the genes responsible for its synthesis are observed in humans. thus, drugs inhibiting enzymes of this pathway are unlikely to interfere with met ...201526323856
predominance of uganda genotype of mycobacterium tuberculosis isolated from ugandan patients with tuberculous lymphadenitis.in uganda, the emerging uganda genotype of mycobacterium tuberculosis is the most common cause of pulmonary tuberculosis (ptb), and accounts for up to 70% of isolates. extrapulmonary tb (eptb) is less studied in uganda.201526323435
simple detection of the is6110 sequence of mycobacterium tuberculosis complex in sputum, based on pcr with graphene oxide.graphene oxide (go) has proven to be a satisfactory dna-sensor platform for applications in enzyme-free signal amplification, fluorescence-based amplification, and nanoparticle-based platforms because of its excellent electrical, thermal, and optical properties. in this study, we designed a novel platform for the fluorescence detection of biomolecules, using a fluorescent dye-labeled primer and go. we applied this system for the detection of the is6110 insertion sequence of the mycobacterium tub ...201526322510
permutations of time and place in tuberculosis.tuberculosis remains a global health pandemic. the current depiction of the mycobacterium tuberculosis life cycle proposes that airborne bacilli are inhaled and phagocytosed by alveolar macrophages, resulting in the formation of a granuloma that ruptures into the airways to reinitiate the infectious cycle. however, this widely proposed model overlooks the fact, established 100 years ago, that the initial site of m tuberculosis implantation is in the lower zones of the lungs, whereas infectious c ...201526321650
[up-to-date applicability of interferon-γ release assays for the diagnosis of tuberculosis].utility of the in-vitro immunodiagnostic methods, based on the detection of interferon-γ released by t-cells after specific mycobacterium tuberculosis antigen stimulation (igra), has been an improvement in the accuracy of the latent tuberculosis infection diagnosis. igra have a well-known higher specificity than the tuberculin skin testing (tst). moreover, they can obtain a larger number of positive results than the tst in immunocompromised patients. igra have shown a high correlation with m. tu ...201526320991
cathepsin g in experimental tuberculosis: relevance for antibacterial protection and potential for immunotherapy.neutrophil serine proteases, such as cathepsin g (cg) and neutrophil elastase (ne), have been implicated in the protective response against infections, including experimental mycobacterial infections. the goal of this study was to explore the role of cg in immunocompetent mice challenged aerogenically with mycobacterium tuberculosis. we used genetically cg- or cg/ne-deficient mice to define the importance of these neutrophil serine proteases for antibacterial protection, granulomatous response, ...201526320257
beijing clades of mycobacterium tuberculosis are associated with differential survival in hiv-negative russian patients.we conducted a prospective study to establish factors associated with survival in tuberculosis patients in russia including social, clinical and pathogen-related genetic parameters. specifically we wished to determine whether different strains/clades of the beijing lineage exerted a differential effect of survival. hiv-negative culture-confirmed cases were recruited during 2008-2010 across samara oblast and censored in december 2011. molecular characterization was performed by a combination of s ...201526319998
comparative metabolic profiling of mce1 operon mutant vs wild-type mycobacterium tuberculosis strains.mycobacterium tuberculosis disrupted in a 13-gene operon (mce1) accumulates free mycolic acids (fm) in its cell wall and causes accelerated death in mice. here, to more comprehensively analyze differences in their cell wall lipid composition, we used an untargeted metabolomics approach to compare the lipid profiles of wild-type and mce1 operon mutant strains. by liquid chromatography-mass spectrometry, we identified >400 distinct lipids significantly altered in the mce1 mutant compared to wild t ...201526319139
identification of a novel immunodominant antigen rv2645 from rd13 with potential as a cell-mediated immunity-based tb diagnostic agent.search for novel specific antigens are urgently needed for the detection of tuberculosis (tb). in this study, we evaluated the diagnostic potential of a novel mycobacterium tuberculosis (m.tb)-specific candidate antigen (rv2645) from dna segment region of differentiation (rd) 13 of m.tb and investigated t-cell recognition during natural infection in humans and experimental mice. rv2645-specific ifn-γ levels were much higher in the peripheral blood mononuclear cells (pbmcs) of tb patients than th ...201526318635
simultaneous staining of sputum smears for acid-fast and lipid-containing myobacterium tuberculosis can enhance the clinical evaluation of antituberculosis treatments.dormant, slow-growing, antibiotic-tolerant mycobacterium tuberculosis undermine the shortening of tuberculosis treatment to less than 6 months and are thought to be characterised by intracellular lipid bodies. antibiotic effects on such persisting bacilli escape evaluation as they cannot be readily cultured. we identified cells containing lipid bodies in sputum smears from 86 newly diagnosed pulmonary tuberculosis patients and monitored these cells daily in 42 patients over the first 14 days of ...201526318558
high-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of mycobacterium tuberculosis glmu.n-acetylglucosamine-1-phosphate uridyltransferase (glmu) is a pivotal bifunctional enzyme, its n and c terminal domains catalyzes uridyltransferase and acetyltransferase activities, respectively. final product of glmu catalyzed reaction, uridine-diphospho-n-acetylglucosamine (udp-glcnac), acts as sugar donor providing glcnac residues in the synthesis of peptidoglycan and a disaccharide linker (d-n-glcnac-1-rhamnose), the key structural components of mycobacterium tuberculosis (m. tuberculosis) c ...201526318557
a case of tuberculous endocarditis in an immunocompetent patient: difficulty with early diagnosis. 201526318510
mdr-tb antibody response (western blot) to fractions of isoniazid and rifampicin resistant antigens of mycobacterium tuberculosis.drug-resistant tb poses a major threat to control of tb worldwide. despite progress in the detection of multidrug-resistant tb (mdr-tb) cases, a major diagnostic gap remains: 55% of reported tb patients estimated to have mdr-tb were not detected in 2013. mdr-tb antigens were conjugated to cnbr-activated sepharose 4b. specific polyclonal antibodies against mdr-tb ags were prepared in rabbits using two boosted injections of the mdr-tb antigen. the antibodies were purified and treated with suscepti ...201526316231
impaired cxcr1-dependent oxidative defence in active tuberculosis patients.much of the pronounced host inflammatory response that occurs in tuberculosis (tb) is related to failed immunity against the invading pathogen. the g-protein coupled receptors cxcr1 and cxcr2 are implicated in important signal transduction pathways in lung inflammatory responses. we investigated the expression and function of these receptors in a simple whole blood model from 24 patients with pulmonary tb and in subjects with latent tb infection (ltbi). healthy controls were recruited from close ...201526316141
evaluation of the quantiferon?-tb gold in-tube assay and tuberculin skin test for the diagnosis of mycobacterium tuberculosis infection in northeastern thailand.the diagnosis of latent mycobacterium tuberculosis infection (ltbi) is currently based on the immunological response of t-cells to m. tuberculosis (mtb) antigens. however, the quantiferon®-tb gold in-tube assay (qft) has not yet been evaluated in the thai adult population.201526342121
development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant mycobacterium tuberculosis.the bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant mycobacterium tuberculosis (mdr-tb) and extensively drug resistant m. tuberculosis (xdr-tb) strains. analytical techniques (1)h and (13)c nuclear magnetic resonance (nmr), fourier transform-ion cyclotron resonance with electrospray ionization (ft-icr/esi), and matrix assisted laser desorption ionization-mass spectrometry (maldi-tof-ms) were used ...201526341133
evaluation of anti-tbgl antibody in the diagnosis of tuberculosis patients in china.tuberculous glycolipid (tbgl) is a component of the mycobacterium tuberculosis cell wall, and anti-tbgl antibodies are used for serodiagnosis of tuberculosis. anti-tbgl igg and iga levels were measured in 45 pulmonary tb patients (ptb), 26 extra-pulmonary tb patients (etb), 16 aids-tb patients, and 58 healthy controls (hc) including 39 health care workers (hw) and 19 newly enrolled students (st). anti-tbgl igg measurements yielded 68.9% and 46.2% sensitivity in ptb and etb, respectively, and 81. ...201526339661
vaccination with an attenuated ferritin mutant protects mice against virulent mycobacterium tuberculosis.mycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. new tools for treatment and prevention of tuberculosis are urgently needed. we previously showed that a ferritin (bfrb) mutant of m. tuberculosis has altered iron homeostasis and increased sensitivity to antibiotics and to microbicidal effectors produced by activated macrophages. most importantly, m. tuberculosis lacking bfrb is strongly attenuated in mice, especially, during the chronic phase of ...201526339659
myelin ultrastructure of sciatic nerve in rat experimental autoimmune neuritis model and its correlation with associated protein expression.to explore the relationship of peripheral nerve ultrastructure and its associated protein expression in experimental autoimmune neuritis (ean). ean was established in lewis rats using an emulsified mixture of p0 peptide 180-199, mycobacterium tuberculosis, and incomplete freund's adjuvant. rats immunized with saline solution were used as a control group. sciatic nerve ultrastructure and immunofluorescence histopathology were measured at the neuromuscular severity peak on day 18 post-induction. c ...201526339349
quantitative detection of cells expressing blac using droplet-based microfluidics for use in the diagnosis of tuberculosis.this paper describes a method for the quantitative detection of cells expressing blac, a β-lactamase naturally expressed by mycobacterium tuberculosis, intended for the diagnosis of tuberculosis. the method is based on the compartmentalization of bacteria in picoliter droplets at limiting dilutions such that each drop contains one or no cells. the co-encapsulation of a fluorogenic substrate probe for blac allows the quantification of bacteria by enumerating the number of fluorescent drops. quant ...201526339319
detection of mycobacterium tuberculosis complex in sputum specimens using a loop-mediated isothermal amplification assay in korea.tuberculosis (tb), an infectious disease caused by mycobacterium tuberculosis complex (mtc), remains one of the leading causes of death in the world. in korea, the current prevalence of multidrug-resistant tb (mdr-tb) poses a major problem. the most common method for diagnosing tb in developing countries is sputum smear microscopy; however, the sensitivity of this test is relatively low and it usually requires well-trained laboratory staff. cultures of mtc require up to several weeks in sophisti ...201526338293
gene expression profiling of mycobacterium tuberculosis lipoarabinomannan-treated macrophages: a role of the bcl-2 family member a1 in inhibition of apoptosis in mycobacteria-infected macrophages.macrophages play an important role in the establishment of infection by intracellular pathogens. mycobacterium tuberculosis is known to inhibit apoptosis and to downregulate immune responses of host cells using various strategies, including activation of peroxisome proliferator-activated receptor (ppar)γ. mannose-capped lipoarabinomannan (manlam) is one of the known bacterial effectors that plays a role in subversion of host immunity and activation of pparγ. here, we have used an unbiased global ...201526337784
evaluation of matricellular proteins in systemic and local immune response to mycobacterium tuberculosis infection.matricellular proteins such as osteopontin (opn), galectin-9 (gal-9), and tenascin-c (tn-c) are expressed not only under normal physiological conditions, but also during infection, inflammation and tumorigenesis. plasma concentrations of matricellular proteins were studied to determine their diagnostic value as potential markers of tuberculosis (tb) activity. it was found that concentrations of opn and tn-c were higher in patients with active tb than in healthy controls and individuals with late ...201526337438
protection by novel vaccine candidates, mycobacterium tuberculosis δmosr and δecha7, against challenge with a mycobacterium tuberculosis beijing strain.mycobacterium tuberculosis, the etiological agent of tuberculosis (tb), infects over two billion people, claiming around 1.5 million lives annually. the only vaccine approved for clinical use against this disease is the bacillus calmette-guérin (bcg) vaccine. unfortunately, bcg has limited efficacy against the adult, pulmonary form of tuberculosis. this vaccine was developed from m. bovis with antigen expression and host specificity that differ from m. tuberculosis. to address these problems, we ...201526363381
[a case of rib tuberculosis and chest wall abscess with multi-drug hypersensitivity reactions].extrapulmonary tuberculosis is the reactivation of the remaining latent organism which spreads during primary infection by the lymphohematogenous way. it should be considered in the differential diagnosis especially in endemic countries for tuberculosis. tuberculosis (tb) treatment is based on the principle of the combined use of several drugs. as a result of the combination therapy there can be life threatening side effects which can lead to improper use of medications and may also cause drug r ...201526313287
e-dna sensor of mycobacterium tuberculosis based on electrochemical assembly of nanomaterials (mwcnts/ppy/pamam).two-step electrochemical patterning methods have been employed to elaborate composite nanomaterials formed with multiwalled carbon nanotubes (mwcnts) coated with polypyrrole (ppy) and redox pamam dendrimers. the nanomaterial has been demonstrated as a molecular transducer for electrochemical dna detection. the nanocomposite mwcnts-ppy has been formed by wrapping the ppy film on mwcnts during electrochemical polymerization of pyrrole on the gold electrode. the mwcnts-ppy layer was modified with p ...201526313137
mutation profiling for detection of isoniazid resistance in mycobacterium tuberculosis clinical isolates.progress in the detection of drug-resistant tb has been underpinned by the development and implementation of new, reliable and rapid diagnostic tools. these rely mostly on the detection of specific mutations conferring resistance to anti-tb drugs. the aim of this study was to search for mutations associated with isoniazid resistance among mycobacterium tuberculosis clinical isolates.201526311839
targeting mycobacterium tuberculosis biotin protein ligase (mtbpl) with nucleoside-based bisubstrate adenylation inhibitors.mycobacterium tuberculosis (mtb), responsible for both latent and symptomatic tuberculosis (tb), remains the second leading cause of mortality among infectious diseases worldwide. mycobacterial biotin protein ligase (mtbpl) is an essential enzyme in mtb and regulates lipid metabolism through the post-translational biotinylation of acyl coenzyme a carboxylases. we report the synthesis and evaluation of a systematic series of potent nucleoside-based inhibitors of mtbpl that contain modifications t ...201526299766
design and synthesis of 11α-substituted bile acid derivatives as potential anti-tuberculosis agents.we have synthesized a series of novel 11α-triazoyl bile acid derivatives. in addition, we also have synthesized n-alkyl and n-acyl derivatives of c-11 amino bile acid esters. all the compounds were evaluated for the inhibitory activity against mycobacterium tuberculosis h37ra (mtb) at 30 μg/ml level. four lead compounds (2b, 3, 7 and 8) were further confirmed from their dose dependent effect against mtb. these compounds were found to be active against dormant and active stage mtb under both in v ...201526299346
setting the gray zone of near-cutoff values in a real-time pcr test for the detection of mycobacterium tuberculosis in an intermediate burden country.recently, molecular detection of mycobacterium tuberculosis in a respiratory specimens is accepted as one of the standard procedures for diagnosis of tuberculosis in korea. when detecting tuberculosis using a real-time polymerase chain reaction (pcr), results showed the repeated near-cutoff values in a specimen make it difficult for the laboratory to give definitive reports as positive or negative.201526299089
comparison and development of pyrazinamide susceptibility testing methods for tuberculosis in thailand.pyrazinamide (pza) plays a critical role in shortening tuberculosis treatment duration and in treating multi-drug resistant tuberculosis (mdr-tb). the standard phenotypic mgit pza susceptibility testing method is imperfect because it is slow and has potential for false resistance. in this study, we evaluated 2 different phenotypic-based methods, quantitative real-time pcr (qpcr) phage assay, and mtt assay, as well as genotypic sequencing. the assay was evaluated on 71 clinical mycobacterium tube ...201526298819
one-pot synthesis of new triazole--imidazo[2,1-b][1,3,4]thiadiazole hybrids via click chemistry and evaluation of their antitubercular activity.a new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. all the intermediates and final molecules were characterised using spectral methods and one of the target compounds (6c) was analysed by the single crystal xrd study. the derivatives were screened for their antimycobacterial activity against mycobacterium tuberculosis h37rv strain. two comp ...201526298500
molecular epidemiology study of mycobacterium tuberculosis and its susceptibility to anti-tuberculosis drugs in indonesia.genotyping of mycobacterium tuberculosis helps to understand the molecular epidemiology of tuberculosis and to address evolutionary questions about the disease spread. certain genotypes also have implications for the spread of infection and treatment. indonesia is a very diverse country with a population with multiple ethnicities and cultures and a history of many trade and tourism routes. this study describes the first attempt to map the molecular epidemiology of tb in the indonesian archipelag ...201526297576
insights from the molecular docking of hydrolytic products of methyl isocyanate (mic) to inhibition of human immune proteins.this study is an attempt to find the reason for immunological suppression in victims of bhopal gas tragedy during 1984 against mycobacterium tuberculosis (mtb) infection. here, we tried to understand this problem by studying interactions between immune proteins associated with susceptibility to tuberculosis and hydrolytic products of methyl isocyanate (mic) released during the tragedy. the hydrolytic products of mic i.e. dimethyl urea, trimethyl urea and trimethyl isocyanurate were docked to dif ...201526297312
rapid detection of mycobacterium tuberculosis complex by real-time pcr in sputum samples and its use in the routine diagnosis in a reference laboratory.tuberculosis (tb) is an infectious disease of global distribution, constituting a serious public health problem in brazil. são paulo state, located in the south-east of brazil, notified 16,580 new tb cases in 2013. the instituto adolfo lutz is a public health reference laboratory for tb diagnosis for all the state. considering that rapid and accurate diagnosis is essential for tb control, the aim of this study was to evaluate the use of an in-house real-time (rt)-pcr assay targeting the mpt64 ge ...201526297002
mir-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages.tuberculosis (tb) is a serious infectious disease that most commonly affects the lungs. macrophages are among the first line defenders against establishment of mycobacterium tuberculosis infection in the lungs. in this study, we found that activation and cytokine production in monocyte-derived macrophages (mdm) from patients with active tb was impaired. mir-223 expression was significantly elevated in monocytes and mdm from patients with tb compared with healthy controls. to determine the functi ...201526296289
confinement-induced drug-tolerance in mycobacteria mediated by an efflux mechanism.tuberculosis (tb) is the world's deadliest curable disease, responsible for an estimated 1.5 million deaths annually. a considerable challenge in controlling this disease is the prolonged multidrug chemotherapy (6 to 9 months) required to overcome drug-tolerant mycobacteria that persist in human tissues, although the same drugs can sterilize genetically identical mycobacteria growing in axenic culture within days. an essential component of tb infection involves intracellular mycobacterium tuberc ...201526295942
new griselimycins for treatment of tuberculosis.griselimycin (gm), a natural product isolated a half century ago, is having a bit of a renaissance. after being known for more than 50 years, it is now being pursued as a treatment for tuberculosis. with the new mechanism of action, excellent in vitro and in vivo activity against sensitive and drug-resistant mycobacterium tuberculosis, and the improved pharmacokinetic properties, the cyclohexyl derivative of gm demonstrates a high translational potential.201526295835
vitamin d, serum 25(oh)d, ll-37 and polymorphisms in a canadian first nation population with endemic tuberculosis.canadian first nation populations have experienced endemic and epidemic tuberculosis (tb) for decades. vitamin d-mediated induction of the host defence peptide ll-37 is known to enhance control of pathogens such as mycobacterium tuberculosis.201526294193
mycobacterium tuberculosis pnca polymorphisms that do not confer pyrazinamide resistance at a breakpoint concentration of 100 micrograms per milliliter in mgit.sequencing of the mycobacterium tuberculosis pnca gene allows for pyrazinamide susceptibility testing. we summarize data on pnca polymorphisms that do not confer resistance at a susceptibility breakpoint of 100 μg/ml pyrazinamide in mgit within a cohort of isolates from south africa and the u.s. centers for disease control and prevention.201526292310
recent advances in the development of vaccines for tuberculosis.tuberculosis (tb) continues to be a dreadful infection worldwide with nearly 1.5 million deaths in 2013. furthermore multi/extensively drug-resistant tb (mdr/xdr-tb) worsens the condition. recently approved anti-tb drugs (bedaquiline and delamanid) have the potential to induce arrhythmia and are recommended in patients with mdr-tb when other alternatives fail. the goal of elimination of tb by 2050 will not be achieved without an effective new vaccine. the recent advancement in the development of ...201526288734
opportunistic infections among people living with hiv (plhiv) with diabetes mellitus (dm) attending a tertiary care hospital in coastal city of south india.hiv/aids and diabetes mellitus are the diseases' known to supress cell mediated immunity and predispose patients for opportunistic infections. hence, we conducted a study to compare the common opportunistic infections (ois) between people living with hiv with dm (plhiv-dm) and plhiv without dm (plhiv).201526287949
macrophage activation by ursolic and oleanolic acids during mycobacterial infection.oleanolic (oa) and ursolic acids (ua) are triterpenes that are abundant in vegetables, fruits and medicinal plants. they have been described as active moieties in medicinal plants used for the treatment of tuberculosis. in this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with mycobacterium tuberculosis (mtb). we evaluated production of nitric oxide (no), reactive oxygen species (ros), and cytokines (tnf-α and tgf-β) as well as expression of cell membrane ...201526287131
a tuberculin skin test survey and the annual risk of mycobacterium tuberculosis infection in gambian school children.a tuberculin skin test (tst) survey was conducted to assess the prevalence of latent tb infection (ltbi) and to estimate the annual risk of m. tuberculosis infection (arti) in gambian school children. the results are expected to contribute to understanding of tuberculosis epidemiology in the gambia.201526465745
construction of a dna vaccine encoding mtb32c and hbha genes of mycobacterium tuberculosis.tuberculosis (tb) is a contagious disease caused by mycobacterium tuberculosis. development of a new vaccine for tuberculosis requires immunogenic antigens capable of inducing suitable and long-lasting t cell immunity. the emergence of multidrugs and extensively drug-resistant strains of m. tuberculosis has made it a global public health concern.201526464766
structural basis of mapping the spontaneous mutations with 5-flurouracil in uracil phosphoribosyltransferase from mycobacterium tuberculosis.tuberculosis (tb) remains the second leading cause of death from an infectious disease globally, despite the incessant efforts to control it. research and development into new tb medicines is imperative for effective tb control; however, new strategies for the rational use of existing drugs, such as through the identification of new drug targets, could also significantly enhance this process. key enzymes involved in the essential metabolic and regulatory pathways are usually sought in the pursui ...201526456658
the microbiome at the pulmonary alveolar niche and its role in mycobacterium tuberculosis infection.advances in next generation sequencing (ngs) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. the presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological diffi ...201526455529
mycobacterium tuberculosis strains modify granular enzyme secretion and apoptosis of human neutrophils.mycobacterium tuberculosis has evolved to employ multiple strategies to avoid an efficient host immune response. accordingly, enzymes are important antimycobacterial elements and apoptosis decides the fate of any cell. hence, we carried out this study to discern the amplitude of two clinical stains (s7 & s10) and a laboratory strain (h37rv) of m. tuberculosis in modifying the release of lytic enzymes and apoptosis of neutrophils from healthy volunteers and pulmonary tuberculosis patients. we det ...201526455524
report: clinical characteristics and treatment experience report of severe pulmonary infection after renal transplantation.this study was to discuss the clinical diagnosis and treatment features of severe pulmonary infections after renal transplantation, in order to improve the cure rate. retrospective research was applied to analyze the 52 cases of patients with serve pulmonary infection after renal transplantation in the department of organ transplantation in people's hospital of zhengzhou from july, 2008 to december, 2013. the pathogens which caused the pulmonary infection after renal transplantation were bacteri ...201526431655
performance of four transport and storage systems for molecular detection of multidrug-resistant tuberculosis.detection of drug-resistant tuberculosis is essential for the control of the disease but it is often hampered by the limitation of transport and storage of samples from remote locations to the reference laboratory. we performed a retrospective field study to evaluate the performance of four supports enabling the transport and storage of samples to be used for molecular detection of drug resistance using the genotype mtbdrplus.201526431352
human nocardia infections: a review of pulmonary nocardiosis.human nocardiosis may present as an acute or a chronic infection. although a saprophyte nocardia spp are responsible for superficial skin infections, pulmonary infections, and disseminated nocardiosis usually involving patients who are immunosuppressed and debilitated. infections in immunocompetent individuals are usually chronic and present non-specific symptoms. invasive and disseminated nocardiosis is common among patients with weakened cellular immune systems. clinical diagnosis of pulmonary ...201526430578
e1 of α-ketoglutarate dehydrogenase defends mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress.enzymes of central carbon metabolism (ccm) in mycobacterium tuberculosis (mtb) make an important contribution to the pathogen's virulence. evidence is emerging that some of these enzymes are not simply playing the metabolic roles for which they are annotated, but can protect the pathogen via additional functions. here, we found that deficiency of 2-hydroxy-3-oxoadipate synthase (hoas), the e1 component of the α-ketoglutarate (α-kg) dehydrogenase complex (kdhc), did not lead to general metabolic ...201526430237
genome comparison of an ancestral isolate and a modern isolate of mycobacterium tuberculosis of the beijing lineage from são paulo, brazil.mycobacterium tuberculosis of the bejing subtype (mtbb) is transmitted efficiently in high burden countries for this genotype. a higher virulence was associated with isolates of the "modern" beijing genotype sub-lineages when compared to "ancient" ones. here, we report the full genomes of the strain representing these two genotypes from brazil, a country with a low incidence of mtbb.201526430044
characterization of cd4/cd8+ αβ and vγ2vδ2+ t cells in hiv-negative individuals with different mycobacterium tuberculosis infection statuses.the immune responses of t cell subsets among patients with different mycobacterium tuberculosis (m.tb) infection statuses [i.e., active tuberculosis (atb), latent tuberculosis infection (ltbi) and non-infection (healthy control, hc)] have not been fully elucidated in hiv-negative individuals. specifically, data are limiting in high tuberculosis epidemic regions in china. to investigate the distributions and functions of t cell subsets (i.e., cd3+, cd4+, cd8+ αβ and vγ2vδ2+ t cells) in hiv-negati ...201526429305
recognizing drug targets using evolutionary information: implications for repurposing fda-approved drugs against mycobacterium tuberculosis h37rv.drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery. such a cost and time-saving approach gains immense importance for pathogens of special interest, such as mycobacterium tuberculosis h37rv. we report a comprehensive approach to repurpose drugs, based on the exploration of evolutionary relationships inferred from the comparative sequence and structural analyses between targets o ...201526429199
a rare case of concomitant tuberculosis of the nose, paranasal sinuses and larynx: clinical, histological and immunohistochemical aspects. a case report.extrapulmonary tuberculosis is a rare condition determined by mycobacterium tuberculosis. it can affect any organ, and has a higher incidence with the increase of hiv infection, or in countries with high pulmonary tuberculosis. diagnosis is difficult, mostly because of non-specific symptoms and a low rate of presentation for medical consult when symptoms do occur. complete diagnosis is usually set by histological, immunohistochemical examinations, and also with polymerase chain reaction (pcr) in ...201526429181
bone marrow aspirate microscopy v. bone marrow trephine biopsy microscopy for detection of mycobacterium tuberculosis infection.tuberculosis (tb) remains a global health problem. according to the 2013 global report on tuberculosis, 8.6 million people developed tb in 2012 and 1.3 million died from the disease. an estimated 13% of people who developed tb in 2012 were hiv-positive, and 75% of these lived in africa. while pulmonary tb is the commonest form of mycobacterium tuberculosis infection, extrapulmonary tb is increasingly being detected in hiv-positive patients. definitive diagnosis of disseminated tb is a challenge ...201526428979
tuberculosis: ph-responsive isoniazid-loaded nanoparticles markedly improve tuberculosis treatment in mice (small 38/2015).on page 5066, j. i. zink, m. a. horwitz, and co-workers use confocal microscopy to demonstrate the avid uptake of ritc-labeled mesoporous silica nanoparticles loaded with the anti-tuberculosis drug isoniazid (shown here in red) by human macrophages (nuclei stained blue with dapi) infected with gfp-expressing mycobacterium tuberculosis (shown here in green).201526450161
serological diagnosis of pulmonary mycobacterium tuberculosis infection by lips using a multiple antigen mixture.there is an urgent need for a simple and accurate test for the diagnosis of human mycobacterium tuberculosis, the infectious agent causing tuberculosis (tb). here we describe a serological test based on light emitting recombinant proteins for the diagnosis of pulmonary mycobacterium tuberculosis infection.201526449888
clarity and pact-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.visualization of infection and the associated host response has been challenging in adult vertebrates. owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ...201526449262
preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages.following infection, hiv establishes reservoirs within tissues that are inaccessible to optimal levels of antiviral drugs or within cells where hiv lies latent, thus escaping the action of anti-hiv drugs. macrophages are a persistent reservoir for hiv and may contribute to the rebound viremia observed after antiretroviral treatment is stopped. in this study, we further investigate the potential of poly(lactic-co-glycolic) acid (plga)-based nanocarriers as a new strategy to enhance penetration of ...201526445538
[tuberculosis].tuberculosis ranges among the most important causes of morbidity and mortality worldwide. the emergence of drug-resistant strains of mycobacterium tuberculosis, especially in the who region europe, is of serious concern. recently, important advances have been achieved in the areas of tuberculosis prevention, diagnosis and treatment and in the management of patients with multidrug-resistant tuberculosis. recent highlights are being presented in this mini-review.201526445253
evaluation of giant african pouched rats for detection of pulmonary tuberculosis in patients from a high-endemic setting.this study established evidence about the diagnostic performance of trained giant african pouched rats for detecting mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (tb) in a high-burden setting.201526445086
targeting mycobacterial enzymes with natural products.tuberculosis (tb) is a recurring threat to contemporary civilization. it affects not only those within developing countries, but has also appeared again in places where it was once considered eradicated. tb co-infection in patients infected by hiv is, at the time of writing, the most common cause of death. in the field of searching for new antimycobacterial drug leads, compounds of natural origin still remain a promising source. the review is intended to gather information about natural products ...201526441042
isoniazid induced motor-dominant neuropathy.isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. a 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. she was treated with vita ...201526440850
mycobacterium tuberculosis impdh in complexes with substrates, products and antitubercular compounds.tuberculosis (tb) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant tb. inosine 5'-monophosphate dehydrogenase 2 (impdh2) from mycobacterium tuberculosis (mtb) is an attractive drug target. the enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of nad+ to nadh. this reaction controls flux into the guanine nucleotide pool. we rep ...201526440283
lack of intracellular replication of m. tuberculosis and m. bovis bcg caused by delivering bacilli to lysosomes in murine brain microvascular endothelial cells.invasion and traversal of the blood-brain barrier (bbb) by mycobacterium tuberculosis cause meningeal tuberculosis (tb) in the central nervous system (cns). meningeal tb is a serious, often fatal disease that disproportionately affects young children. the mechanisms involved in cns invasion by m. tuberculosis bacilli are poorly understood. in this study, we microscopically examined endosomal trafficking and measured survival of m. tuberculosis and m. bovis bacille calmette-guérin (bcg) bacilli i ...201526440149
dynamics of immune parameters during the treatment of active tuberculosis showing negative interferon gamma response at the time of diagnosis.in the performance of interferon gamma release assays (igra) for the diagnosis of tuberculosis (tb) infection, false-negative results are a major obstacle. in active tb patients, treatment-dependent changes of the negative test results remain unknown.201526439971
ppe26 induces tlr2-dependent activation of macrophages and drives th1-type t-cell immunity by triggering the cross-talk of multiple pathways involved in the host response.the pathophysiological functions and the underlying molecular basis of pe /ppe proteins of m. tuberculosis remain largely unknown. in this study, we focused on the link between ppe26 and host response. we demonstrated that ppe26 can induce extensive inflammatory responses in macrophages through triggering the cross-talk of multiple pathways involved in the host response, as revealed by itraq-based subcellular quantitative proteomics. we observed that ppe26 is able to specifically bind to tlr2 le ...201526439698
one of these is not like the others.a mycobacterium tuberculosis meta mutant that is auxotrophic for methionine is unlike other auxotrophic mutants of this important species as methionine starvation results in rapid death instead of cessation of growth. evidence suggests that this phenotype results from starvation affecting essential pathways that utilize s-adenosylmethionine in addition to methionine.201526439291
peptidoglycan synthesis in mycobacterium tuberculosis is organized into networks with varying drug susceptibility.peptidoglycan (pg), a complex polymer composed of saccharide chains cross-linked by short peptides, is a critical component of the bacterial cell wall. pg synthesis has been extensively studied in model organisms but remains poorly understood in mycobacteria, a genus that includes the important human pathogen mycobacterium tuberculosis (mtb). the principle pg synthetic enzymes have similar and, at times, overlapping functions. to determine how these are functionally organized, we carried out who ...201526438867
esters of pyrazinoic acid are active against pyrazinamide-resistant strains of mycobacterium tuberculosis and other naturally resistant mycobacteria in vitro and ex vivo within macrophages.pyrazinamide (pza) is active against major mycobacterium tuberculosis species (m. tuberculosis, m. africanum, and m. microti) but not against m. bovis and m. avium. the latter two are mycobacterial species involved in human and cattle tuberculosis and in hiv coinfections, respectively. pza is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to form the active metabolite pyrazinoic acid (poa). as a result of this mechanism, resis ...201526438493
mycobacterium tuberculosis nucleic acid amplification tests reduce nosocomial tuberculosis exposure in intensive care units: a nationwide cohort study.this retrospective national surveillance study investigated the burden of and risk factors for nosocomial exposure of pulmonary tuberculosis (tb) in intensive care units.201526437626
identification and validation of aspartic acid semialdehyde dehydrogenase as a new anti-mycobacterium tuberculosis target.aspartic acid semialdehyde dehydrogenase (asadh) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. mutations in the asadh gene encoding asadh produce an inactive enzyme, which is lethal. therefore, in this study, we investigated the hypothesis that asadh represents a new anti-mycobacterium tuberculosis (mtb) target. an asadh promoter-replacement mutant mtb, designated mtb::asadh, in which asadh gene ...201526437401
comparative proteomic analysis of aminoglycosides resistant and susceptible mycobacterium tuberculosis clinical isolates for exploring potential drug targets.aminoglycosides, amikacin (ak) and kanamycin (km) are second line anti-tuberculosis drugs used to treat tuberculosis (tb) and resistance to them affects the treatment. membrane and membrane associated proteins have an anticipated role in biological processes and pathogenesis and are potential targets for the development of new diagnostics/vaccine/therapeutics. in this study we compared membrane and membrane associated proteins of ak and km resistant and susceptible mycobacterium tuberculosis iso ...201526436944
partial saturation of menaquinone in mycobacterium tuberculosis: function and essentiality of a novel reductase, menj.menaquinone (mk) with partially saturated isoprenyl moieties is found in a wide range of eubacteria and archaea. in many gram-positive organisms, including mycobacteria, it is the double bond found in the β-isoprene unit that is reduced. mass spectral characterization of menaquinone from mycobacterial knockout strains and heterologous expression hosts demonstrates that rv0561c (designated menj) encodes an enzyme which reduces the β-isoprene unit of menaquinone in mycobacterium tuberculosis, form ...201526436137
tubercular nodular episcleritis: a case report.tuberculosis (tb) is an infectious disease caused by the acid-fast bacillus mycobacterium tuberculosis and is an important cause of death worldwide. tuberculosis most commonly affects the lungs, but has many extrapulmonary manifestations as well, including intraocular involvement. tubercular nodular episcleritis is a very rare presentation and no such case in an adult male has been reported in the literature. herein, we present the very first case of tubercular nodular episcleritis in a 30-year- ...201526435978
analysis of the molecular evolution of the mycobacterium tuberculosis drug-resistant gene rpob in asia using a bayesian evolutionary method.tuberculosis (tb) is a serious communicable disease throughout the world. re-emergence of the tb epidemic is aggravated by the circulation of multidrug-resistant mycobacterium tuberculosis strains, and more than half of new cases have occurred in asia. therefore, it is important to understand the gene mutations underlying the development of rifampicin resistance in asia.201526427147
update in mycobacterium tuberculosis lung disease 2014. 201526426784
a mycobacterium tuberculosis dormancy antigen differentiates latently infected bacillus calmette-guérin-vaccinated individuals.ifn-γ release assays (igras) are better indicators of mycobacterium tuberculosis infection than the tuberculin skin test (tst) in bacillus calmette-guérin (bcg)-vaccinated populations. however, igras do not discriminate active and latent infections (ltbi) and no gold standard for ltbi diagnosis is available. thus, since improved tests to diagnose m. tuberculosis infection are required, we assessed the efficacy of several m. tuberculosis latency antigens. bcg-vaccinated healthy donors (hd) and tu ...201526425695
distribution and transmission of mycobacterium tuberculosis complex lineages among children in peri-urban kampala, uganda.to gain insight into the transmission of tuberculosis (tb) in peri-urban kampala-uganda, we performed a household contact study using children as a surrogate for recent transmission of mycobacterium tuberculosis (mtb). using this approach, we sought to understand m. tuberculosis complex (mtbc) lineage diversity, distribution and how these relate to tb transmission to exposed children.201526424324
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