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in vitro isolation and characterization of oxazolidinone resistant mycobacterium tuberculosis.oxazolidinones are promising candidates for the treatment of mycobacterium tuberculosis infections. we isolated linezolid resistant strains from h37rv (euro-american) and hn878 (east-asian) strains; resistance frequency was similar in both strains. mutations were identified in ribosomal protein l3 (rplc) and the 23s rrna (rrl). all mutant strains were cross resistant to sutezolid; a subset were cross-resistant to chloramphenicol. mutations in rrl led to growth impairment and decreased fitness th ...201728760892
susceptibility of mycobacterium tuberculosis cytochrome bd oxidase mutants to compounds targeting the terminal respiratory oxidase, cytochrome c.we deleted subunits i (cyda) and ii (cydb) of the mycobacterium tuberculosis cytochrome bd menaquinol oxidase. the resulting δcyda and δcydab mutants were hypersusceptible to compounds targeting the mycobacterial bc1 menaquinol-cytochrome c oxidoreductase, and exhibited bioenergetic profiles indistinguishable from strains deficient in the abc-type transporter, cyddc, predicted to be essential for cytochrome bd assembly. these results confirm cydab and cyddc as potential targets for drugs aimed a ...201728760899
tpl2 promotes innate cell recruitment and effector t cell differentiation to limit citrobacter rodentium burden and dissemination.tumor progression locus 2 (tpl2) is a serine-threonine kinase that regulates th1 differentiation, secretion of the inflammatory cytokine ifnγ, and host defense against the intracellular pathogens toxoplasma gondii, listeria monocytogenes, and mycobacterium tuberculosis however, there is relatively little known about the contribution of tpl2 to th17 differentiation and immune cell function during infection with an extracellular pathogen. the goal of this study was to determine whether tpl2 influe ...201728760932
cutaneous squamous cell carcinoma in lupus vulgaris caused by drug resistant mycobacterium tuberculosis.tuberculosis (tb) is still a major public health problem in the world, with many factors contributing to this burden, including poor living conditions, overcrowding, poverty, malnutrition, illiteracy, and rapid spread of human immunodeficiency virus infection. cutaneous tuberculosis is a less common form of extrapulmonary tuberculosis, and in this paucibacillary form the diagnosis depends on histopathology, tuberculin positivity, and response to treatment. the diagnosis is even more difficult in ...201728761842
ribosome rescue inhibitors kill actively growing and nonreplicating persister mycobacterium tuberculosis cells.the emergence of mycobacterium tuberculosis (mtb) strains that are resistant to most or all available antibiotics has created a severe problem for treating tuberculosis and has spurred a quest for new antibiotic targets. here, we demonstrate that trans-translation is essential for growth of mtb and is a viable target for development of antituberculosis drugs. we also show that an inhibitor of trans-translation, kkl-35, is bactericidal against mtb under both aerobic and anoxic conditions. biochem ...201728762275
complete auxotrophy for unsaturated fatty acids requires deletion of two sets of genes in mycobacterium smegmatis.the synthesis of unsaturated fatty acids in mycobacterium smegmatis is poorly characterized. bioinformatic analysis revealed four putative fatty acid desaturases in its genome, one of which, msmeg_1886, is highly homologous to desa3, the only palmitoyl/stearoyl desaturase present in the mycobacterium tuberculosis genome. a msmeg_1886 deletion mutant was partially auxotrophic for oleic acid and viable at 37°c and 25°c, although with a long lag phase in liquid medium. fatty acid analysis suggested ...201728762586
detecting new mycobacterium tuberculosis infection: time for a more nuanced interpretation of quantiferon conversions. 201728763239
multifocal tubercular dactylitis: a rare presentation of skeletal tuberculosis in an adult.tubercular dactylitis is an uncommon form of osteo-articular tuberculosis seen in children. multifocal involvement, simultaneously involving hands and feet is extremely uncommon. here we report an adult patient with tubercular dactylitis involving multiple digits of both hands and second digit of right foot in absence of any risk factors like immunodeficiency or any debilitating condition. the patient was successfully treated with anti-tubercular drugs for six months. mycobacterium tuberculosis ...201728764233
evaluation of antimycobacterial, leishmanicidal and antibacterial activity of three medicinal orchids of arunachal pradesh, india.the ethnic population of arunachal pradesh uses a number of orchids as such, or in decoction for various ailments. three untapped orchids namely, rhynchostylis retusa, tropidia curculioides and satyrium nepalense, traditionally used in tuberculosis, asthma and cold stage of malaria in folk medicine, were selected for the present study.201728764749
tuberculous pericarditis treated with steroid in a dialysis patient.mycobacterium tuberculosis has spread worldwide and its mortality rate had been very high. the prevention technology and antituberculosis (tb) chemotherapy has improved its prognosis. however, immunocompromised patients, such as those who had hiv infection, older age and on haemodialysis, are still at high risk of tb infection. tb pericarditis is a common cause of constrictive pericarditis and its mortality remains high. early diagnosis and initiation of appropriate therapy are critical to impro ...201728765186
isothermal point mutation detection: toward a first-pass screening strategy for multidrug-resistant tuberculosis.point mutations in dna are useful biomarkers that can provide critical classification of disease for accurate diagnosis and to inform clinical decisions. conventional approaches to detect point mutations are usually based on technologies such as real-time polymerase chain reaction (pcr) or dna sequencing, which are typically slow and require expensive lab-based equipment. while rapid isothermal strategies such as recombinase polymerase amplification (rpa) have been proposed, they tend to suffer ...201728766343
dendritic cells that phagocytose apoptotic macrophages loaded with mycobacterial antigens activate cd8 t cells via cross-presentation.while homeostatic apoptosis is immunologically silent, macrophage apoptosis during mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. to examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing lpqh. the apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nu ...201728767693
engaging the cd40-cd40l pathway augments t-helper cell responses and improves control of mycobacterium tuberculosis infection.mycobacterium tuberculosis (mtb) impairs dendritic cell (dc) functions and induces suboptimal antigen-specific cd4 t cell immune responses that are poorly protective. mucosal t-helper cells producing ifn-γ (th1) and il-17 (th17) are important for protecting against tuberculosis (tb), but the mechanisms by which dcs generate antigen-specific t-helper responses during mtb infection are not well defined. we previously reported that mtb impairs cd40 expression on dcs and restricts th1 and th17 respo ...201728767735
impact of childhood malnutrition on host defense and infection.the global impact of childhood malnutrition is staggering. the synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, ...201728768707
identification of compounds that decrease numbers of mycobacteria in human macrophages in the presence of serum amyloid p.mϕs are a heterogeneous population of cells and include classically activated mϕs (m1) and alternatively activated mϕs (m2). mϕs can change from m1 to m2 and vice versa in response to environmental stimuli. serum amyloid p (sap) is a constitutive plasma protein that polarizes mϕs to an m2 phenotype, and part of this effect is mediated through fcγri receptors. in an effort to find ways to alter mϕs phenotypes, we screened for compounds that can block the sap-fcγri interaction. from a screen of 30 ...201728768708
immunodominance of adenovirus-derived cd8(+) t cell epitopes interferes with the induction of transgene-specific immunity in adenovirus-based immunization.adenovirus (ad)-based immunization is a popular approach in vaccine development, and ad-based vectors are renowned for their potential to induce strong cd8(+) t cell responses to the encoded transgene. surprisingly, we found before in the mouse friend retrovirus (fv) model that ad-based immunization did not induce cd8(+) t cell responses to the fv leader-gag-derived immunodominant epitope gagl85-93 we show now that induction of gagl85-93-specific cd8(+) t cells was highly effective when leader-g ...201728768877
storage and retrieval of mycobacterium tuberculosis on filter paper strips. 199428769224
the role of rapid slide culture in the diagnosis and management of pulmonary tuberculosis.rapid slide culture method using human blood medium was utilized for the primary culture of mycobacterium tuberculosis and the results obtained were compared with results of smear examination of sputum specimens from fresh cases of pulmonary tuberculosis. smear and rapid slide culture results of a total of 320 patients were analyzed. slide culture was positive in 104 cases whereas smears were positive in 90 cases. early culture confirmation in 7 days coupled with positivity better than smear exa ...199528769283
multidrug resistant tuberculosis - biomechanism, epidemiology and management strategies.muitidrug resistant tuberculosis has shown an alarming increase and this assumes added importance in view of the increasing number of hiv infected patients. this article reviews the biomechanism of resistance and discusses the present stategies that are available and recommended to tackle the rising incidence of tuberculosis due to resistant mycobacteria.199728769486
the dynamic immunomodulatory effects of vitamin d3 during mycobacterium infection.mycobacterium tuberculosis ( mtb), is a highly infectious airborne bacterium. previous studies have found vitamin d3 to be a key factor in the defense against mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. mycobacterium smegmatis was used in our study as a surrogate of mtb. we hypothesized that the continuous presence of vitamin d3, as well as the level of severity of infection would differentially modulate host cell immune ...201728770668
teixobactin and its analogues: a new hope in antibiotic discovery.increasing bacterial resistance against current antibiotics and lack of new molecules to combat bacterial resistance are key challenges to global health. there is, therefore, a continuing need to develop new antibiotics. teixobactin, a cyclic undecapeptide, displays excellent antibacterial activities against a range of pathogenic bacteria, such as methicillin-resistant staphylococcus aureus (mrsa) and mycobacterium tuberculosis. interestingly, it operates by multiple modes of actions and is bact ...201728770988
comparative proteomic profiles reveal characteristic mycobacterium tuberculosis proteins induced by cholesterol during dormancy conditions.cholesterol has been reported to play an important role during mycobacterium tuberculosis infection and during its dormant state inside the host. we present the determination of proteomic profiles of m. tuberculosis h37rv in the presence of cholesterol as the sole carbon source under exponential growth and in two in vitro dormancy phases (nrp1 and nrp2). using 2d-page, we detected that m. tuberculosis expressed a high diversity of proteins in both exponential and non-replicative phases. we also ...201728771131
a novel nanoemulsion vaccine induces mucosal interleukin-17 responses and confers protection upon mycobacterium tuberculosis challenge in mice.tuberculosis (tb), caused by mycobacterium tuberculosis (mtb) is contracted via aerosol infection, typically affecting the lungs. mycobacterium bovis bacillus calmette-guerin (bcg) is the only licensed vaccine and has variable efficacy in protecting against pulmonary tb. additionally, chemotherapy is associated with low compliance contributing to development of multidrug-resistant (mdr) and extensively drug-resistant (xdr) mtb. thus, there is an urgent need for the design of more effective vacci ...201728774560
an evaluation study on phenotypical methods and real-time pcr for detection of mycobacterium tuberculosis in sputa of two health centers in iran.for further confirmation of the previous in-house real-time pcr and cyp 141 target as a rapid and cheap diagnostic technique and a new target for direct detection of mycobacterium tuberculosis, we evaluated and compared the results of smear, culture and real-time pcr in sputa that were collected from 2 health centers. moreover we tried to evaluate the diagnostic accuracy of phenotypical methods for detection of tuberculosis that have been applied in two health centers of iran.201728775822
malignant metastatic deposits in an immunocompromised patient-could this be tuberculosis?we report the case of a 50-year-old female renal transplant patient who developed disseminated deposits initially diagnosed as metastatic malignancy of unknown primary. she declined a tissue diagnosis but subsequently developed recurrent sepsis and symptomatic unilateral pleural effusion. mycobacterium tuberculosis was cultured from pleural fluid. following introduction of anti-tuberculous medications, her symptoms improved rapidly and the progression of her disseminated deposits stabilized. tub ...201728775851
comprehensive definition of human immunodominant cd8 antigens in tuberculosis.despite widespread use of the bacillus calmette-guerin vaccine, tuberculosis, caused by infection with mycobacterium tuberculosis, remains a leading cause of morbidity and mortality worldwide. as cd8(+) t cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia ankara expressing ag85a that failed to demonstrate efficacy, also failed to induce a cd8(+) t cell response, an effective tuberculosis vaccine may need to induce cd8(+) t cells. however, little is ...201728775896
fighting tuberculosis by drugs targeting nonreplicating mycobacterium tuberculosis bacilli.current tuberculosis (tb) treatment requires 6 months of combination therapy with isoniazid (inh), rifampin (rif), pyrazinamide (pza), and ethambutol for active tb and 9 months of inh or 3 months of rifapentine (rfp) + inh for latent tb. the lungs of patients with active and latent tb contain heterogeneous mixtures of cellular and caseous granulomas harboring mycobacterium tuberculosis bacilli ranging from actively replicating (ar) to nonreplicating (nr), phenotypically drug-resistant stages. se ...201728776518
common bacterial isolates, clinical outcome and tb meningitis in children admitted at morogoro regional referral hospital, tanzania.bacterial meningitis is still one of the major causes of deaths, disabilities, and mental retardation in children in morogoro region. to study the current meningitis burden, we evaluated the common bacterial isolates and clinical outcome of the disease in the region.201728776526
humoral immune responses in mice immunized with region of difference dna vaccine constructs of pumvc6 and pumvc7.we aimed to study the antigen-specific antibody responses in mice immunized with recombinant dna vaccines constructs of pumvc6 and pumvc7, containing rd1 and rd9 genes of mycobacterium tuberculosis.201728776528
rapid laboratory diagnosis of pulmonary tuberculosis.tuberculosis (tb) ranks as the second leading cause of death from an infectious disease worldwide. early diagnosis of mycobacterium tuberculosis in clinical samples becomes important in the control of tb both for the treatment of patients and for curbing of disease transmission to the others in the community. the study objective was to perform ziehl-neelsen (zn) staining, fluorochrome staining, line probe assay (lpa), and loop-mediated isothermal amplification (lamp) assay for rapid detection of ...201728776530
preservation of sputum samples with cetylpyridinium chloride (cpc) for tuberculosis cultures and xpert mtb/rif in a low-income country.culture contamination with environmental bacteria is a major challenge in tuberculosis (tb) laboratories in hot and humid climate zones. we studied the effect of cetylpyridinium chloride (cpc) preservation on culture results and performance of xpert mtb/rif.201728778186
discovery of new leads against mycobacterium tuberculosis using scaffold hopping and shape based similarity.bm212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant mycobacterium tuberculosis and mycobacteria residing in macrophages. however, it was not pursued because of its poor pharmacokinetics and toxicity profile. our goal was to design and synthesize new antimycobacterial bm212 analogs with lower toxicity and better pharmacokinetic profile. using the scaffold hopping approach, three structurally diverse h ...201728778369
2-n-arylthiazole inhibitors of mycobacterium tuberculosis.to develop agents for the treatment of infections caused by mycobacterium tuberculosis, a novel phenotypic screen was undertaken that identified a series of 2-n-aryl thiazole-based inhibitors of intracellular mycobacterium tuberculosis. analogs were optimized to improve potency against an attenuated bsl2 h37ra laboratory strain cultivated in human macrophage cells in vitro. the insertion of a carboxylic acid functionality resulted in compounds that retained potency and greatly improved microsoma ...201728778468
clinical diagnostic value of simultaneous amplification and testing for the diagnosis of sputum-scarce pulmonary tuberculosis.since 20% of pulmonary tuberculosis (ptb) patients are asymptomatic, the early detection of ptb is a challenge particularly in sputum-scarce patients and diagnostic accuracy based solely on clinical characteristics and chest x-ray/ct scans are not always satisfactory. the ampsure simultaneous amplification and testing method for the detection of mycobacterium tuberculosis (sat-tb assay) is an alternative approach to diagnose ptb. in the present study, we analyzed the usefulness of the sat-tb ass ...201728779754
direct detection of mycobacterium tuberculosis and drug resistance in respiratory specimen using abbott realtime mtb detection and rif/inh resistance assay.abbott realtime mtb (abbott-rt) in conjunction with abbott realtime mtb rif/inh resistance (abbott-rif/inh) is a new, high-throughput automated nucleic acid amplification platform (abbott-mdr) for detection of mycobacterium tuberculosis complex (mtbc) and the genotypic markers for rifampicin (rif) and isoniazid (inh) resistance directly from respiratory specimens. this prospective study evaluated the diagnostic performance of this new platform for mtbc and multidrug-resistant tuberculosis (mdr-t ...201728780247
targeting mycobacterium tuberculosis sensitivity to thiol stress at acidic ph kills the bacterium and potentiates antibiotics.mycobacterium tuberculosis (mtb) must sense and adapt to immune pressures such as acidic ph during pathogenesis. the goal of this study was to isolate compounds that inhibit acidic ph resistance, thus defining virulence pathways that are vulnerable to chemotherapy. here, we report that the compound ac2p36 selectively kills mtb at acidic ph and potentiates the bactericidal activity of isoniazid, clofazimine, and diamide. we show that ac2p36 activity is associated with thiol stress and causes an e ...201728781126
asymmetric structure of the dimerization domain of phor, a sensor kinase important for the virulence of mycobacterium tuberculosis.the phop-phor two-component system is essential for the virulence of mycobacterium tuberculosis (mtb) and therefore represents a potential target for developing novel antituberculosis therapies. however, little is known about the mechanism by which this two-component system regulates the virulence. in this study, we demonstrated that a phor mutant mtb strain has phenotypes similar to those of a phop mutant, suggesting that phop and phor work in the same pathway to regulate mtb virulence. we dete ...201728782049
in vitro activity of alpha-viniferin isolated from the roots of carex humilis against mycobacterium tuberculosis.this study explores the antitubercular activity of α-viniferin, a bioactive phytochemical compound obtained from carex humilis. α-viniferin was active against both drug-susceptible and -resistant strains of mycobacterium tuberculosis at mic50s of 4.6 μm in culture broth medium and mic50s of 2.3-4.6 μm inside macrophages and pneumocytes. in combination with streptomycin and ethambutol, α-viniferin exhibited an additive effect and partial synergy, respectively, against m. tuberculosis h37rv. α-vin ...201728782713
impact of larger sputum volume on xpert(®) mtb/rif assay detection of mycobacterium tuberculosis in smear-negative individuals with suspected tuberculosis.as a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (afb) negative samples, larger volumes of sputum (5-10 ml) were tested with xpert(®) mtb/rif from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. despite larger volumes, this strategy had a suboptimal sensitivity of 50% (4/8).201728783093
guanine nucleotide exchange factor -h1 promotes inflammatory cytokine production and intracellular mycobacterial elimination in macrophages.mycobacterium tuberculosis (m.tb), which causes tuberculosis, is a host-adapted intracellular pathogen that can live within macrophages owning to its ability to arrest phagolysosome biogenesis. the guanine nucleotide exchange factor h1 (gef-h1) may contribute to the phagocytosis of bacteria by macrophages through mediating the crosstalk between microtubules and the actin cytoskeleton. its role in shigella infection has been determined but little is known about the role of gef-h1 in mycobacterial ...201728783414
plasmid-based high-resolution melting analysis for accurate detection of rpob mutations in mycobacterium tuberculosis isolates from moroccan patients.rapid diagnosis of drug resistance in tuberculosis (tb) is pivotal for the timely initiation of effective antibiotic treatment to prevent the spread of drug-resistant strains. the development of low-cost, rapid and robust methods for drug-resistant tb detection is highly desirable for resource-limited settings.201728784099
characterization of a minimal type of promoter containing the -10 element and a guanine at the -14 or -13 position in mycobacteria.three key promoter elements, -10, -35, and t-15g-14n, are recognized by the σ subunit of rna polymerase. among them, promoters with the -10 element and either of -35 or t-15g-14n consensuses are known to efficiently initiate transcription, but recent systematic analyses have identified a large group of promoters in mycobacterium tuberculosis that contain only a -10 consensus. how these promoters initiate transcription remains poorly understood. here, we show that promoters containing the -10 ele ...201728784819
enrichment by hybridisation of long dna fragments for nanopore sequencing.enrichment of dna by hybridisation is an important tool which enables users to gather target-focused next-generation sequence data in an economical fashion. current in-solution methods capture short fragments of around 200-300 nt, potentially missing key structural information such as recombination or translocations often found in viral or bacterial pathogens. the increasing use of long-read third-generation sequencers requires methods and protocols to be adapted for their specific requirements. ...201628785419
catabolism of the cholesterol side chain in mycobacterium tuberculosis is controlled by a redox-sensitive thiol switch.mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), is a highly successful human pathogen and has infected approximately one-third of the world's population. multiple drug resistant (mdr) and extensively drug resistant (xdr) tb strains and coinfection with hiv have increased the challenges of successfully treating this disease pandemic. the metabolism of host cholesterol by mtb is an important factor for both its virulence and pathogenesis. in mtb, the cholesterol side ch ...201728786661
diagnosing diffuse lung disease in children in a middle-income country: the role of open lung biopsy.a tertiary care hospital situated in a middle-income country with a high burden of tuberculosis (tb) and human immunodeficiency virus (hiv) infection.201728786794
immuno-diagnosis of mycobacterium tuberculosis in sputum, and reduction of timelines for its positive cultures to within 3 h by pathogen-specific thymidylate kinase expression assays.laboratory diagnosis of tuberculosis (tb) is traditionally based on microscopy and or culture. microscopy is however, only sensitive to a specified degree of bacillary load not present in hiv co-infected persons. traditional cultures of mycobacterium tuberculosis (m. tb), on the other hand, take weeks to read-thereby delaying the critical decision whether or not, to treat. although nucleic acids amplification tests (naats) applied directly on sputum or cultures can increase the sensitivity for t ...201728789704
prioritization of natural compounds against mycobacterium tuberculosis 3-dehydroquinate dehydratase: a combined in-silico and in-vitro study.enormous efforts have been endeavored to develop inhibitors against the potential therapeutic target, mycobacterium tuberculosis 3-dehydroquinate dehydratase (mtbdhqase) to combat resistance. over a dozen of small molecules have been crystallized to characterize the structural basis of the inhibition. however, the studies accomplished so far, have not incorporated all the essential interactions of these complexes simultaneously, to identify the novel inhibitors. therefore, an attempt was made to ...201728789944
mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in spain 1998-2005.although the incidence of tuberculosis (tb) is gradually decreasing in spain, there is an increase in the proportion of foreign-born cases. this changing scenario is slowly shifting the local tb epidemiology from endemic to imported cases with an increased risk for multidrug-resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis complex. mdr/xdr strains from spain (n=366 mtbc isolates, 1 strain per patient) isolated between 1998 and 2005 were retained for this ...201728789982
recent advances in tuberculosis diagnostic techniques.tuberculosis is re-emerging as an important cause of morbidity and mortality in man. this article outlines current strategies available for the diagnosis of tuberculosis, and its applicability. fluorescent staming, modified culture methods, antigen detection, elisa based assays against various antigen preparation and recent advances in molecular techniques have been outlined. present strategies being developed at armed forces medical college for the early diagnosis, speciation, antibiotic sensit ...200028790679
trehalose polyphleates, external cell wall lipids in mycobacterium abscessus, are associated with the formation of clumps with cording morphology, which have been associated with virulence.mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by mycobacterium tuberculosis. when grown in agar medium, m. abscessus strains generate rough (r) or smooth colonies (s). r morphotypes are more virulent than s morphotypes. in searching for the virulence factors responsible for this difference, r morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. furthermo ...201728790995
a genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis.thiolactomycin (tlm) is a thiotetronate antibiotic that selectively targets bacterial fatty acid biosynthesis through inhibition of the β-ketoacyl-acyl carrier protein synthases (kasi/ii) that catalyse chain elongation on the type ii (dissociated) fatty acid synthase. it has proved effective in in vivo infection models of mycobacterium tuberculosis and continues to attract interest as a template for drug discovery. we have used a comparative genomics approach to uncover the (hitherto elusive) bi ...201628791099
role of ergothioneine in microbial physiology and pathogenesis.l-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria and some fungi. in contrast to other low molecular weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological ph, which makes it resistant to autoxidation. ergothioneine regulates microbial physiology and enables survival of the microbes under stressful conditions encountered in their natural environments. in particular, ergothioneine enables p ...201728791878
[morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis.201728791993
bedaquiline and linezolid for extensively drug-resistant tuberculosis in pregnant woman.a woman with extremely drug-resistant tuberculosis treated with a drug regimen including linezolid and bedaquiline during her last 3 weeks of pregnancy gave birth to a child without abnormalities. no fetal toxicities were noted by 2 years after delivery. this drug combination might be safe during the late third trimester of pregnancy.201728792382
environmental aspects related to tuberculosis and intestinal parasites in a low-income community of the brazilian amazon.we carried out a cross-sectional study from january to december 2015 on 1,425 inhabitants from a floating population in the brazilian amazon (murinin district, pará state) to describe the population-based prevalence of tuberculosis (tb) from 2011 to 2014, recent tb contacts (rcts) latently infected with mycobacterium tuberculosis (ltbi) , the coverage of the local health network, socio-environmental factors, and frequency of intestinal parasitic infection (ipi). we found that the sanitary struct ...201728793025
cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of pa-824 via il-10 in mycobacterium tuberculosis disease.pa-824 is a novel bicyclic nitroimidazole anti-tuberculosis (tb) drug. cordyceps sinensis (berk.) sacc. (cs) was proven to be a good immunomodulatory compound. this research aimed to investigate the effect of cs on pa-824 in mycobacterium tuberculosis (m.tb) infected mice (female cba/j mice, 6 to 8 weeks of age and 20±2 g of weight). mice were randomly assigned to 4 groups: pa-824, cs, pa-824+cs, and control. to verify the effect of pa-824 and cs on m.tb, after drug administration, mice lungs we ...201728793052
ligation of dectin-2 with a novel microbial ligand promotes adjuvant activity for vaccination.the development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. while most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. microbes such as fungi and mycobacterium tuberculosis require th17 and th1 cells for resistance, and engage the c-type lectin receptors including dectin-2. herein, we discovered a novel dectin-2 li ...201728793349
genotype mtbdrplus assay for screening and characterization of isoniazid and rifampicin resistance-associated mutations in multidrug-resistant mycobacterium tuberculosis from india.multidrug resistant tuberculosis (mdr-tb) is rising and world health organization has recommended the line probe assay (lpa) for screening. in this study we assess lpa at a tertiary care center from north india in 1758 samples from suspected mdr-tb cases. all smear positive and/or m.tuberculosis culture confirmed cases (n=1170) were subjected to genotype-mtbdr assay. amongst these the majority were retreatment cases, smear positive at diagnosis (n=637). mdr prevalence of 7.8% was observed with t ...201728793376
optic disc swelling in a patient with tuberculous meningitis: a diagnostic challenge.we discuss the diagnostic challenge in an adult patient presented with purely ocular symptoms diagnosed with tuberculous meningitis (tbm). a 38-year-old woman presented with bilateral painless blurring of vision. there were bilateral sixth cranial nerve palsy and bilateral optic disc swelling. optic nerve function tests were normal. patient was lucid with no signs of meningism. brain imaging were normal. she had a positive mantoux test, high erythrocyte sedimentation rate but no clinical evidenc ...201728794092
potential of high-affinity, slow off-rate modified aptamer (somamer) reagents for mycobacterium tuberculosis proteins as tools for infection models and diagnostic applications.direct pathogen detection in blood to diagnose active tuberculosis (tb) has been difficult, due to low levels of circulating antigens or due to the lack of specific, high-affinity binding reagents and reliable assays with adequate sensitivity. we sought to determine whether slow off-rate modified aptamer (somamer) reagents with sub-nanomolar affinity for m. tuberculosis (mtb) proteins (antigen 85a, 85b, 85c, groes, groel2, dnak, cfp10, kad, cfp2, rpll and tpx) could be useful to diagnose tubercu ...201728794178
membrane filtration is suitable to reliably eliminate mycobacterium tuberculosis from saliva for therapeutic drug monitoring.tuberculosis (tb) remains an infectious disease of a worldwide concern.….201728794182
characterization of mycobacterium tuberculosis-specific cells using mhc class ii tetramers reveals phenotypic differences related to hiv infection and tuberculosis disease.a major challenge for the development of an effective vaccine against tuberculosis (tb) is that the attributes of protective cd4(+) t cell responses are still elusive for human tb. infection with hiv type 1 is a major risk factor for tb, and a better understanding of hiv-induced alterations of mycobacterium tuberculosis-specific cd4(+) t cells that leads to failed host resistance may provide insight into protective t cell immunity to tb. a total of 86 participants from a tb-endemic setting, eith ...201728794233
transmission is a noticeable cause of resistance among treated tuberculosis patients in shanghai, china.it is generally believed that drug resistance among treated tuberculosis (tb) patients is as a result of acquired drug resistance due to inappropriate treatment. previous studies have shown that primary drug resistance caused by transmission also plays a role among treated cases. differentiating the two types of drug resistance will help in developing appropriate strategies for control of drug resistant tuberculosis. in this study, we tested the hypothesis that drug resistance among treated tb p ...201728794425
evaluation of genexpert mtb/rif for determination of rifampicin resistance among new tuberculosis cases in west and northwest iran.despite a mycobacterium tuberculosis control programme and anti-tuberculosis drugs, drug-resistant tuberculosis (dr-tb) is one of the most serious public health issues worldwide. rapid laboratory diagnosis of m. tuberculosis is needed for the diagnosis of multidrug-resistant (mdr) tb and to find the optimal treatment protocol. the purpose of this study was to detect resistance to rifampicin in new cases of tb using the genexpert mtb/rif (m. tuberculosis/rifampicin) assay and the standard proport ...201728794886
the potency of chicken egg yolk immunoglobulin (igy) specific as immunotherapy to mycobacterium tuberculosis infection.the aim of this study was to characterize of chicken egg yolk immunoglobulins (igys) specific as immunotherapy to mycobacterium tuberculosis complex (mtbc) infection. lohmann laying hens were immunized intramuscularly with antigenic of mtbc. egg yolk was separated from egg white, and igy antibody was then purified by multiple polyethylene glycols 6000 extraction and ammonium sulfate purification steps. the igy anti-mtbc concentration in egg yolk increased at 2 weeks and it reached a maximum at 4 ...201728795022
how long does antimycobacterial antibiotic-loaded bone cement have in vitro activity for musculoskeletal tuberculosis?antibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. however, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking.201728795294
the utility of immunohistochemistry in mycobacterial infection: a proposal for multimodality testing.mycobacterium species are slow growing bacteria that cause significant morbidity and mortality worldwide. because of the relative rarity of mycobacterial infections, potential for detection of nonpathogenic environmental contaminants, and substantial costs associated with molecular diagnostics, effective screening methods are needed to identify samples most suitable for molecular testing. while anatomic pathology specimens can be utilized to identify characteristic histologic inflammatory patter ...201728795999
prevalence and molecular characterization of second-line drugs resistance among multidrug-resistant mycobacterium tuberculosis isolates in southwest of china.this study aimed to investigate the prevalence of multidrug-resistant tuberculosis (mdr-tb) isolates resistant to the second-line antituberculosis drugs (slds) and its association with resistant-related gene mutations in mycobacterium tuberculosis (m.tb) isolates from southwest of china. there were 81 isolates resistant to at least one of the slds among 156 mdr-tb isolates (81/156, 51.9%). the rates of general resistance to each of the drugs were as follows: ofx (66/156, 42.3%), kan (26/156, 16. ...201728798931
splenic tuberculosis and multifocal serpiginoid choroiditis.serpiginoid multifocal choroiditis is a distinct morphological identity with a reported causal association with mycobacterium tuberculosis. we report a case of serpiginoid multifocal choroiditis in a 17-year-old boy who was suffering from isolated splenic tuberculosis. he was treated with systemic steroids along with anti-tubercular treatment with good visual recovery. this case was unique as no other organs except spleen and choroid showed tubercular involvement. we hereby emphasize association ...201728798995
mechanism of rv2837c from mycobacterium tuberculosis remains controversial. 201728801352
reply to valadares and woo: mechanism of rv2837c from mycobacterium tuberculosis remains controversial. 201728801353
protein o-mannosylation deficiency increases lprg-associated lipoarabinomannan release by mycobacterium tuberculosis and enhances the tlr2-associated inflammatory response.protein o-mannosylation is crucial for the biology of mycobacterium tuberculosis but the key mannosylated protein(s) involved and its(their) underlying function(s) remain unknown. here, we demonstrated that the m. tuberculosis mutant (δpmt) deficient for protein o-mannosylation exhibits enhanced release of lipoarabinomannan (lam) in a complex with lprg, a lipoprotein required for lam translocation to the cell surface. we determined that lprg is o-mannosylated at a unique threonine position by ma ...201728801649
lysx gene is differentially expressed among mycobacterium tuberculosis strains with different levels of virulence.antimicrobial peptides (amps) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. indeed, it has been described that this line of defense is essential to control infection. however, mycobacterium tuberculosis (mtb) has developed mechanisms to avoid amps activity, for instance lysx adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the amps. in the ...201728802397
mycobacterium tuberculosis myma is a tlr2 agonist that activate macrophages and a th1 response.cell wall of mycobacterium tuberculosis (m.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. myma (rv3083), a 55 kda m.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following m.tb internalization in macrophage. in this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (tlrs) engagement and subsequent signaling. our results showed ...201728802400
differences in igg responses against infection phase related mycobacterium tuberculosis (mtb) specific antigens in individuals exposed or not to mtb correlate with control of tb infection and progression.tuberculosis (tb) occurs in only 3-10% of mycobacterium tuberculosis (mtb) infected individuals, suggesting that natural immunity can contain mtb infection, although this remains poorly understood. next to t-cells, a potentially protective role for b-cells and antibodies has emerged recently. however, the mtb antigens involved remain ill-defined. here, we investigated in a tb-endemic setting igg levels against 15 mtb antigens, representing various phases of mtb infection and known to be potent h ...201728802401
sustained expression of devr/dosr during long-term hypoxic culture of mycobacterium tuberculosis.devr/dosr is a key mediator of 'dormancy' adaptation in mycobacterium tuberculosis in response to gaseous stresses such as hypoxia that inhibit aerobic mode of respiration. in the present study, a temporal analysis over a 1 year period has revealed robust expression of representative devr regulon genes devr, hspx and tgs1, during long-term 'dormancy' adaptation to hypoxia. notably, a predominant proportion of long-term hypoxia-adapted bacteria were characterized by their inability to grow on sol ...201728802402
detection of mycobacterium tuberculosis from paraffin-embedded tissues by genexpert mtb/rif.genexpert mtb/rif (xpert) assay, a rapid and automated system based on real-time pcr and molecular beacon technology, proved to be a sensitive and specific tool capable of detecting mycobacterium tuberculosis and rifampin resistance in clinical specimens. in this study we provide a xpert-dedicated successful protocol for processing paraffin-embedded tissue and assess the feasibility of the xpert assay-based tuberculosis (tb) diagnosis on these specimens, thus proving the xpert assay as a valuabl ...201728802405
immunological characterization of latent tuberculosis infection in a low endemic country.the diagnosis of a latent tuberculosis infection (ltbi) is based on detection of immunity against mycobacterium tuberculosis (mtb). the tuberculin skin test (tst), the quantiferon (qft) and a prolonged lymphocyte stimulation test using either esat-6/cfp-10 (lst-ec) or ppd (lst-ppd) were evaluated in a cohort of 495 individuals, suspected to have ltbi, in a low endemic country. while the tst and lst-ppd were both positive in the majority (75%) of individuals, only one third responded in the lst-e ...201728802407
down-regulation of malate synthase in mycobacterium tuberculosis h37ra leads to reduced stress tolerance, persistence and survival in macrophages.malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-coa. this reaction helps in bypassing the tca cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide tca cycle intermediates. malate synthase (glcb) is encoded by mra_1848 of mycobacterium tuberculosis h37ra (mtb-ra). we developed a knockdown (kd) mtb-ra strain by down-regulating glcb. the ...201728802408
exploring the potential of t7 bacteriophage protein gp2 as a novel inhibitor of mycobacterial rna polymerase.over the past six decades, there has been a decline in novel therapies to treat tuberculosis, while the causative agent of this disease has become increasingly resistant to current treatment regimens. bacteriophages (phages) are able to kill bacterial cells and understanding this process could lead to novel insights for the treatment of mycobacterial infections. phages inhibit bacterial gene transcription through phage-encoded proteins which bind to rna polymerase (rnap), thereby preventing bact ...201728802409
evaluation of 24-locus miru-vntr genotyping in mycobacterium tuberculosis cluster investigations in four jurisdictions in the united states, 2006-2010.the u.s. centers for disease control and prevention (cdc) uses a combination of spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units-variable number of tandem repeats (miru-vntr) analyses as part of the national tb genotyping service (ntgs). the ntgs expansion from 12-locus miru-vntr (miru12) to 24-locus miru-vntr (miru24) in 2009 enhanced the ability to discriminate mycobacterium tuberculosis strains. in the current study, we investigated the miru24 conc ...201728802410
the minipig as an animal model to study mycobacterium tuberculosis infection and natural transmission.in endemic countries more than 20% of tuberculosis (tb) cases are in infants and children. current animal models study tb during adulthood but animal models for infant tb are scarce. here we propose that minipigs can be used as an animal model to study adult, adolescent and infant tb including natural transmission. in these studies, two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with h ...201728802411
mycobacterium tuberculosis sige mutant st28 used as a vaccine induces protective immunity in the guinea pig model.with more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. the only vaccine available against this disease, the attenuated strain mycobacterium bovis, bcg is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. consequently, the development of an effective anti-tuberculosis vaccine is a major ...201728802412
effect of dmso on protein structure and interactions assessed by collision-induced dissociation and unfolding.given the frequent use of dmso in biochemical and biophysical assays, it is desirable to understand the influence of dmso concentration on the dissociation or unfolding behavior of proteins. in this study, the effects of dmso on the structure and interactions of avidin and mycobacterium tuberculosis (mtb) cyp142a1 were assessed through collision-induced dissociation (cid) and collision-induced unfolding (ciu) as monitored by nanoelectrospray ionization-ion mobility-mass spectrometry (nesi-im-ms) ...201728803470
rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?one-third of the world's population is infected with mycobacterium tuberculosis (m.tb.). latent tuberculosis infection (ltbi) can progress to tuberculosis disease, the leading cause of death by infection. rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against m.tb. what are the advantages of each for ltbi or tuberculosis treatment? areas covered: we review studies assessing the pharmacokinetics (pk), pharmacodynamics (pd), drug interaction risk, safety, an ...201728803492
the potential of a portable, point-of-care electronic nose to diagnose tuberculosis.tuberculosis (tb) is the leading cause of death due to an infectious disease worldwide. especially in low-income countries, new diagnostic techniques that are accessible, inexpensive and easy-to-use, are needed to shorten transmission time and initiate treatment earlier.201728804027
prevalence and treatment outcome of extensively drug-resistant tuberculosis plus additional drug resistance from the national clinical center for tuberculosis in china: a five-year review.the objective of this study was to explore the prevalence and primary clinical outcomes of extensively drug-resistant tuberculosis plus addition resistance to all drug tested (xdr-tb-plus) between 2011 and 2015 in beijing chest hospital.201728804028
a multiple-antigen detection assay for tuberculosis diagnosis based on broadly reactive polyclonal antibodies.detection of circulating mycobacterium tuberculosis (m. tuberculosis) antigens is promising in tuberculosis (tb) diagnosis. however, not a single antigen marker has been found to be widely expressed in all tb patients. this study is aimed to prepare broadly reactive polyclonal antibodies targeting multiple antigen markers (multi-target antibodies) and evaluate their efficacies in tb diagnosis.201728804606
linking high-throughput screens to identify moas and novel inhibitors of mycobacterium tuberculosis dihydrofolate reductase.though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. each approach provides different information, and understanding their results can provide hypotheses for a mechanism of action (moa) and reveal actionable chemical matter. here, we describe a framework for identifying efficacy targets of bioactive compounds. high throughput biophysical profiling against ...201728806050
new synthetic lipid antigens for rapid serological diagnosis of tuberculosis.during pulmonary tuberculosis (ptb) antibodies are generated to trehalose esters of mycolic acids which are cell wall lipids of mycobacterium tuberculosis (mtb). attempts have been made to use these complex natural mixtures in serological tests for ptb diagnosis.201728806423
assessment of tuberculosis spatial hotspot areas in antananarivo, madagascar, by combining spatial analysis and genotyping.tuberculosis (tb) remains a public health problem in madagascar. a crucial element of tb control is the development of an easy and rapid method for the orientation of tb control strategies in the country. our main objective was to develop a tb spatial hotspot identification method by combining spatial analysis and tb genotyping method in antananarivo.201728806916
simultaneous detection of 13 key bacterial respiratory pathogens by combination of multiplex pcr and capillary electrophoresis.lower respiratory tract infections continue to pose a significant threat to human health. it is important to accurately and rapidly detect respiratory bacteria. to compensate for the limits of current respiratory bacteria detection methods, we developed a combination of multiplex polymerase chain reaction (pcr) and capillary electrophoresis (mpce) assay to detect thirteen bacterial pathogens responsible for lower respiratory tract infections, including streptococcus pneumoniae, haemophilus influ ...201728807095
allium sativum constituents exhibit anti-tubercular activity in vitro and in raw 264.7 mouse macrophage cells infected with mycobacterium tuberculosis h37rv.long duration of treatment, side-effects of currently used anti-tubercular drugs and emergence of drug-resistant forms of mycobacterium tuberculosis (mtb) warrants the need to develop new drugs to tackle the scourge of tuberculosis (tb). garlic is an edible plant reported to have anti-tubercular activity. however, previous researches on anti-tubercular effect of garlic were focused mostly on preliminary in vitro screening.201728808382
microencapsulated solid lipid nanoparticles as a hybrid platform for pulmonary antibiotic delivery.solid lipid nanoparticles (sln) containing rifabutin (rfb), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. to facilitate their pulmonary delivery, the rfb-loaded sln were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. confocal analysis microscopy showed that microspheres are spherical and that sln are efficiently microencapsulated a ...201728809501
[analysis of infection and drug-resistance in 6 107 cases of extrapulmonary tuberculosis in chengdu area].objective: to analyze the infection and drug resistance of extrapulmonary tuberculosis, in order to provide useful references for prevention and treatment of tuberculosis (tb). methods: a total of 6 107 suspected cases of extrapulmonary tuberculosis, including lymph node, pleural, peritoneal, meningeal, urinary tract, and bone tuberculosis, were collected retrospectively from january 2013 to december 2015 in public health clinical center of chengdu. there were 4 033 male and 2 074 female patient ...201728810312
outcomes from patients with presumed drug resistant tuberculosis in five reference centers in brazil.the implementation of rapid drug susceptibility testing (dst) is a current global priority for tb control. however, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pdr-tb) evaluated under field conditions in high burden countries.201728810911
the capacity of mycobacterium tuberculosis to survive iron starvation might enable it to persist in iron-deprived microenvironments of human granulomas.this study was conducted to investigate the role of iron deprivation in the persistence of mycobacterium tuberculosis we present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation m. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. transcriptomics and metabolomic analyses indicated that the persistence of m. tuberculosis under iron starvation is dependent on strict control of endo ...201728811344
the mycobacterial phosphatase ptpa regulates the expression of host genes and promotes cell proliferation.mycobacterium tuberculosis ptpa is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-jnk, p-p38, and p-vps33b, leading to suppression of host innate immunity. here we show that, in addition, ptpa enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as gadd45a). ptpa can bind directly to the promoter region of ga ...201728811474
delayed effects of transcriptional responses in mycobacterium tuberculosis exposed to nitric oxide suggest other mechanisms involved in survival.mycobacterium tuberculosis has succeeded as a human pathogen for tens of thousands of years thanks to its ability to resist and adapt to the adverse conditions it encounters upon infection. bacterial adaptation to stress is commonly viewed in the context of transcriptional regulation, with the implicit expectation that an initial transcriptomic response is tightly coupled to an ensuing proteomic response. however, after challenging m. tuberculosis with nitric oxide we found that the rapid transc ...201728811595
recombinant expression and biochemical characterization of mycobacterium tuberculosis 3fe-4s ferredoxin rv1786.ferredoxins are iron-sulfur protein that mediate electron transfer in cytochrome p450 mono-oxygenase (cyp)-related catalytic reactions in a wide variety of organisms. rv1786 is a putative ferredoxin, encoded by a gene located downstream of the gene encoding cyp143a1 in the mycobacterium tuberculosis genome. however, the structure and function of rv1786 have remained unclear. here, the recombinant mtb rv1786 was expressed, purified as a his-tagged form and characterized with [3fe-4s] clusters as ...201728812125
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