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neutrophils: double agents for tb.nitric oxide restricts growth of mycobacterium tuberculosis by repressing neutrophilic inflammation.201728615363
strain-based hla association analysis identified hla-drb1*09:01 associated with modern strain tuberculosis.tuberculosis (tb) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. human leukocyte antigen (hla) class ii molecules play an important role in the host immune system. however, no study has assessed the association between hla class ii genes and susceptibility to tb caused by specific strains. this study investigated the possible association of hla class ii genes with tb caused by modern and ancient mycobacterium tuberculosis (mtb). the stud ...201728612994
[addiction of toxin-antitoxin systems to a chaperone in mycobacterium tuberculosis]. 201728612721
[prediction and analysis of epitopes in clpp2 of mycobacterium tuberculosis].to predict and analyze the antigenic epitopes in mycobacterium tuberculosis protein caseinolytic protease p2 (clpp2), and explore its possibility to be applied as a new tuberculosis (tb) vaccine and drug development target.201728612535
comparative study of genexpert mtb/rif assay and multiplex pcr assay for direct detection of mycobacterium tuberculosis in suspected pulmonary tuberculosis patients.pulmonary tuberculosis (ptb) is one of the major infectious diseases in developing countries. the objective of this study was to compare rapid diagnostics technique, genexpert mtb/rif (genexpert) and multiplex pcr assay (mpcr) targeting is6110 segment and mpb64 gene for direct detection of mycobacterium tuberculosis (mtb) in suspected ptb patients. a cross sectional study was carried among 105 sputum samples from suspected ptb patients to evaluate genexpert and multiplex pcr who visited national ...201728612135
antimicrobial activity of quinazolin derivatives of 1,2-di(quinazolin-4-yl)diselane against mycobacteria.mycobacterium tuberculosis (m. tuberculosis) is one of the leading causes of morbidity and mortality. currently, the emergence of drug resistance has an urgent need for new drugs. in previous study, we found that 1,2-di(quinazolin-4-yl)diselane (dqyd), a quinazoline derivative, has anticancer activities against many cancers. however, whether dqyd has the activity of antimycobacterium is still little known. here our results show that dqyd has a similar value of the minimum inhibitory concentratio ...201728612027
diametric role of the latency-associated protein acr1 of mycobacterium tuberculosis in modulating the functionality of pre- and post-maturational stages of dendritic cells.it is instrumental for the mycobacterium tuberculosis (mtb) to persist within its host in dormancy. mtb represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (acr1). therefore, it is imperative to understand how throughout dormancy, mtb employs acr1 to regulate the host immunity. this study reveals that acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (dcs). in the cu ...201728611779
alterations in conformational topology and interaction dynamics caused by l418a mutation leads to activity loss of mycobacterium tuberculosis isocitrate lyase.mycobacterium tuberculosis isocitrate lyase (mtbicl) is a key enzyme of the glyoxylate cycle that catalyzes the cleavage of isocitrate to succinate and glyoxylate and is a potential antituberculosis drug target. the aim of this research was to explore the structural alterations induced by l418a point mutation that caused the loss of enzyme activity. in-depth structural analyses were carried out for understanding the influence of l418a mutation using techniques, viz. molecular dynamics, principal ...201728610921
high-resolution ct findings of pulmonary tuberculosis in liver transplant patients.to assess the high-resolution computed tomography (hrct) findings in liver transplant patients diagnosed with pulmonary mycobacterium tuberculosis infection.201728610889
molecular mechanisms of action, resistance, detection to the first-line anti tuberculosis drugs: rifampicin and pyrazinamide in the post whole genome sequencing era.recent studies in addition to studies based on whole genome sequencing (wgs) of clinical isolates of mycobacterium tuberculosis (mtb) from diverse geographical regions have provided useful insights into the mechanisms of drug resistance. of importance, are some of the findings pertaining to mechanisms of resistance to two of the first-line anti-tuberculosis (tb) drugs, namely, rifampicin (rif) and pyrazinamide (pza). for example, the implication of mutations in rpoa and rpoc genes that act as co ...201728610794
the role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs.novel treatment strategies for tuberculosis are urgently needed. many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. the aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. the concentration- and time-dependent mycobacterial ...201728610791
comparative study of genotypes of mycobacterium tuberculosis from a northern indian setting with strains reported from other parts of india and neighboring countries.this study was carried out to characterize mycobacterium tuberculosis population in ghatampur, kanpur, north india, by spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (miru-vntrs) typing. a total of 335 isolates were genotyped by spoligotyping and central asian (cas) sub-lineage was the most prevalent, comprising 59.1% of all isolates. other lineages were: east-african indian (eai) (19.10%), t (5.07%), beijing (3.28%), manu (2.98%), x (2.68%), s (0 ...201728610789
spolsimilaritysearch - a web tool to compare and search similarities between spoligotypes of mycobacterium tuberculosis complex.spoligotyping is one of the most commonly used polymerase chain reaction (pcr)-based methods for identification and study of genetic diversity of mycobacterium tuberculosis complex (mtbc). despite its known limitations if used alone, the methodology is particularly useful when used in combination with other methods such as mycobacterial interspersed repetitive units - variable number of tandem dna repeats (miru-vntrs). at a worldwide scale, spoligotyping has allowed identification of information ...201728610787
a brief history of tuberculosis in the czech lands.tuberculosis currently remains a serious medical problem, therefore increased attention is being paid to this disease. paleopathological studies focused on the monitoring of morbid changes in skeletal remains of historical populations facilitate a detailed study of the development of this disease. they provide direct evidence of the existence of tuberculosis and its past forms. in addition to literary and iconographic sources, the present study is focused on recording the findings of bone tuberc ...201728610786
chemokines additional to ifn-γ can be used to differentiate among mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.current diagnostic tests for tuberculosis (tb) remain limited in their ability to discriminate between active tb (atb) and latent tb infection (ltbi). early clearance (ec) of tb by individuals exposed to mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. we measured and compared secreted chemokines in the plasma fraction from 48 atb, 38 ltbi, 162 presumed ec and 39 healthy controls (hc) using the quantiferon(®)-tb gold in-tube assay. single chemokine markers were l ...201728610785
molecular investigation of active binding site of isoniazid (inh) and insight into resistance mechanism of s315t-mtkatg in mycobacterium tuberculosis.multi drug resistant tuberculosis is a major threat for mankind. resistance against isoniazid (inh), targeting mtkatg protein, is one of the most commonly occurring resistances in mdr tb strains. s315t-mtkatg mutation is widely reported for inh resistance. despite having knowledge about the mechanism of inh, exact binding site of inh to mtkatg is still uncertain and proposed to have three presumable binding sites (site-1, site-2, and site-3). in the current study docking, molecular dynamics simu ...201728610784
assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model.the aim of the study is to compare counting of colony forming units (cfu), the time to positivity (ttp) assay and the molecular bacterial load (mbl) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. cfu counting, ttp and the mbl assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. mice were treated for 24 weeks with 4 treatment arms: isoniazid (h) - rifampicin (r) - pyrazinamide (z ...201728610782
using genotyping to delineate tuberculosis transmission in long-term care facilities: single facility 4-year experience.residents in long-term care facilities (ltcfs) are vulnerable to tuberculosis (tb) transmission; however, to delineate possible routes of tb transmission in ltcfs is difficult. this study aimed to address the use of regular genotyping surveillance to delineate tb transmission in ltcfs.201728610564
selective killing of dormant mycobacterium tuberculosis by marine natural products.the dormant phenotype acquired by mycobacterium tuberculosis during infection poses a major challenge in disease treatment, since these bacilli show tolerance to front-line drugs. therefore, it is imperative to find novel compounds that effectively kill dormant bacteria. by screening 4,400 marine natural product samples against dual-fluorescent m. tuberculosis under both replicating and nonreplicating conditions, we have identified compounds that are selectively active against dormant m. tubercu ...201728607021
mir-20b inhibits mycobacterium tuberculosis induced inflammation in the lung of mice through targeting nlrp3.tuberculosis (tb) is one of immune-related disorders. although dysregulation of mirnas has been implicated in innate and adaptive immune response, the specific effect of mir-20b on tb has not been documented. in this study, downregulation of mir-20b and upregulation of nlrp3 were observed in macrophages of tb patients, increased levels of inflammatory factors secretion were observed in serum of tb patients. next, we established a tb mice model by using m. tuberculosis infection and intravenous i ...201728606793
poncet's disease in human immunodeficiency virus: a case report.poncet's disease is a rare reactive polyarthritis associated with active tuberculosis and no evidence of mycobacterium tuberculosis in the affected joint.201728606166
isolation of anti-mycobacterial compounds from curtisia dentata (burm.f.) c.a.sm (curtisiaceae).tuberculosis is counted amongst the most infectious and lethal illnesses worldwide and remains one of the major threats to human health. the aim of the current study was to isolate and characterize anti-mycobacterial compounds present in curtisia dentata (burm.f.) c.a.sm , a medicinal plant reportedly used in the treatment of tuberculosis, stomach ailments and sexually transmitted infections.201728606081
structure-based screening and molecular dynamics simulations offer novel natural compounds as potential inhibitors of mycobacterium tuberculosis isocitrate lyase.mycobacterium tuberculosis is the etiological agent of tuberculosis in humans and is responsible for more than two million deaths annually. m. tuberculosis isocitrate lyase (mtbicl) catalyzes the first step in the glyoxylate cycle, plays a pivotal role in the persistence of m. tuberculosis, which acts as a potential target for an anti-tubercular drug. to identify the potential anti-tuberculosis compound, we conducted a structure-based virtual screening of natural compounds from the zinc database ...201728605994
performance of the quantamatrix multiplexed assay platform system for the differentiation and identification of mycobacterium species.the purpose of this study was to evaluate the usefulness of a new diagnostic multiplexed bead-based bioassay (quantamatrix multiplexed assay platform; qmap) system with shape-encoded silica microparticles for the rapid and accurate detection and identification of 23 mycobacterial species/groups, including mycobacterium tuberculosis complex (mtbc).201728604333
drug resistant pulmonary tuberculosis mimicking a flu-like syndrome in an elderly man: an atypical case report.despite remarkable reductions in its incidence and mortality, tuberculosis (tb) continues to be a major health burden globally. pulmonary tb occasionally challenges physicians, either due to tb's ability to mimic many different conditions or because of the increasing number of drug-resistant mycobacterium tuberculosis isolates. here we present a case of pulmonary tb with both characteristics and a brief review of the relevant literature.201728603235
anti-fungal and anti-mycobacterial activity of plants of nuevo leon, mexico.severe fungal infections, particularly those caused by candida spp, have increased in recent decades and are associated with an extremely high rate of morbidity and mortality. since plants are an important source of potentially bioactive compounds, in this work the antifungal activity of the methanol extracts of 10 plants (acacia rigidula, buddleja cordata, cephalanthus occidentalis, juglans nigra, parkinsonia aculeata, parthenium hysterophorus, quercus canbyi, ricinus communis, salvia coccinea ...201728603107
evaluation of the bactec mgit 960 system and the resazurin microtiter assay for susceptibility testing of mycobacterium tuberculosis to second-line drugs.drug resistance in tuberculosis is a major threat to public health and control of the disease worldwide. given the need of a rapid and accurate detection of mycobacterium tuberculosis resistance to second-line drugs, this study evaluated the performance of the bactec mgit 960 for second-line, drug susceptibility testing in comparison with the resazurin microtiter assay (rema), in order to implement the automated methodology in the diagnostic routine of a reference laboratory. drug susceptibility ...201728601653
rifampin stability and solution concentration enhancement through amorphous solid dispersion in cellulose ω-carboxyalkanoate matrices.tuberculosis (tb) is a deadly infectious disease; approximately 2 billion people are currently latently infected with the causative agent mycobacterium tuberculosis. approximately 8 million new active cases and 2 million deaths due to tb are recorded annually.(1) rifampin (rif) is a vital first-line tb treatment drug. its effectiveness is hampered by the high dose required (600 mg 1×/day) and by its moderate, variable bioavailability. these issues can be explained by rif instability at gastric p ...201728601524
croi 2017: complications and comorbidities of hiv disease and its treatment.complications of hiv disease remained a major focus at the 2017 conference on retroviruses and opportunistic infections (croi), and included studies focused on noncommunicable chronic diseases (eg, cardiovascular disease, obesity, bone disease, and malignancies) and opportunistic infections (mycobacterium tuberculosis and cryptococcosis). progress in identifying predictors of specific complications as well as interventions for the prevention and treatment of these comorbidities are summarized be ...201728598792
new structural classes of antituberculosis agents.tuberculosis (tb), one of the deadliest diseases is shattering the health and socioeconomic status of the society. the emergence of multidrug resistant (mdr) and extremely drug resistant (xdr) strains has provided unprecedented lethal character to tb. the development of mdr and xdr strains of tb results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. because of the development of rapid resistance by mycobacterium tuberculosis, research ...201728598559
anti-mycobacterial evaluation of 7-chloro-4-aminoquinolines and hologram quantitative structure-activity relationship (hqsar) modeling of amino-imino tautomers.in an ongoing research program for the development of new anti-tuberculosis drugs, we synthesized three series (a, b, and c) of 7-chloro-4-aminoquinolines, which were evaluated in vitro against mycobacterium tuberculosis (mtb). now, we report the anti-mtb and cytotoxicity evaluations of a new series, d (d01-d21). considering the active compounds of series a (a01-a13), b (b01-b13), c (c01-c07), and d (d01-d09), we compose a data set of 42 compounds and carried out hologram quantitative structure- ...201728598408
in vitro activity of sitafloxacin against mycobacterium tuberculosis with gyra/b mutations isolated in japan.sitafloxacin (sfx) is a new fluoroquinolone (fq) that has shown a strong bactericidal effect against mycobacterium tuberculosis (mtb) in vitro. however, data on sfx efficacy against mtb with gyra/b mutations and its epidemiological cut-off (ecoff) value remain limited. therefore, we evaluated and compared the in vitro activity of sfx against gyra/b-mutant mtb to that of moxifloxacin (mfx), levofloxacin (lfx) and ciprofloxacin (cfx), and determined the ecoff for sfx.201728598311
[genetic recombiniation and protein expression detection of listeria-based tuberculosis vaccine candidates.]genetic construction of tuberculosis vaccine candidates based on listeria(l.) monocytogenes,l.ivanovii,and evaluation their protein expression,in order to provide a novel method for research on tuberculosis controlling.201628598105
digitizing medicines for remote capture of oral medication adherence using co-encapsulation.high-resolution measurement of medication adherence is essential to personalized drug therapy . an fda-cleared device, using an edible ingestion sensor (is), external wearable patch and paired mobile device, can detect and record ingestion events. oral medications must be combined with an is to generate precise 'digitized-medication' ingestion records. we developed a gmp-protocol to repackage oral medications with the is within certified capsugel® capsules, termed co-encapsulation (coe). a rando ...201728597911
pathology of tuberculosis: how the pathology of human tuberculosis informs and directs animal models.tuberculosis (tb) is a chronic inflammatory disease caused by the pathogenic bacterium mycobacterium tuberculosis. a wide variety of host- and pathogen-associated variables influence the clinical manifestation of tb in different individuals within the human population. as a consequence, the characteristic granulomatous lesions that develop within the lung are heterogeneous in size and cellular composition. due to the lack of appropriate tissues from human tb patients, a variety of animal models ...201728597826
mycobacterial biofilms: revisiting tuberculosis bacilli in extracellular necrotizing lesions.under detergent-free in vitro conditions, mycobacterium tuberculosis, the etiological agent of tuberculosis in humans, spontaneously forms organized multicellular structures called biofilms. moreover, in vitro biofilms of m. tuberculosis are more persistent against antibiotics than their single-cell planktonic counterparts, thereby raising questions about the occurrence of biofilms in the host tissues and their significance in persistence during chemotherapy of tuberculosis. in this article, we ...201728597824
oxidative phosphorylation as a target space for tuberculosis: success, caution, and future directions.the emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. the mycobacterium tuberculosis complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the ab ...201728597820
killing mycobacterium tuberculosis in vitro: what model systems can teach us.tuberculosis is one of the most successful human diseases in our history due in large part to the multitude of virulence factors exhibited by the causative agent, mycobacterium tuberculosis. understanding the pathogenic nuances of this organism in the context of its human host is an ongoing topic of study facilitated by isolating cells from model organisms such as mice and non-human primates. however, m. tuberculosis is an obligate intracellular human pathogen, and disease progression and outcom ...201728597814
mycobacterium tuberculosis in the face of host-imposed nutrient limitation.coevolution of pathogens and host has led to many metabolic strategies employed by intracellular pathogens to deal with the immune response and the scarcity of food during infection. simply put, bacterial pathogens are just looking for food. as a consequence, the host has developed strategies to limit nutrients for the bacterium by containment of the intruder in a pathogen-containing vacuole and/or by actively depleting nutrients from the intracellular space, a process called nutritional immunit ...201728597811
first insight into the molecular epidemiology of mycobacterium tuberculosis isolates from the minority enclaves of southwestern china.yunnan is a province located in southwestern china. the aim of this study was to investigate the genetic diversity of mycobacterium tuberculosis (mtb) strains circulating in yunnan province. we used spoligotyping and a 12-locus high-resolution vntr set to identify a total of 271 mtb isolates collected from six prefectures' yunnan. all the 271 patients were classified as 11 different ethnic groups, including 133 han patients (49.1%) and 138 minority patients (50.9%). spoligotyping analyses reveal ...201728596961
epigenetic regulation of matrix metalloproteinase-1 and -3 expression in mycobacterium tuberculosis infection.in pulmonary tuberculosis (tb), the inflammatory immune response against mycobacterium tuberculosis (mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. matrix metalloproteinase (mmp)-1 is a host enzyme critical for the development of cavitation. mmp expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in mtb-associated induction of mmp-1 is unk ...201728596772
role of second-line injectable antituberculosis drugs in the treatment of mdr/xdr tuberculosis.second-line injectable antituberculosis drugs (aminoglycosides and capreomycin) are the main drugs used in the management of resistant tuberculosis. their preserved efficacy in the case of multi-drug-resistant bacillus is counterbalanced by frequent adverse events. adverse events are linked to the drugs themselves and to the recommended 8-month period of parenteral administration. in numerous countries facing a high incidence of multi-drug-resistant tuberculosis, treatment is administered by int ...201728595939
prevalence and risk factors for latent tuberculosis infection among healthcare workers in nampula central hospital, mozambique.healthcare workers in high tuberculosis burdened countries are occupationally exposed to the tuberculosis disease with uncomplicated and complicated tuberculosis on the increase among them. most of them acquire mycobacterium tuberculosis but do not progress to the active disease - latent tuberculosis infection. the objective of this study was to assess the prevalence and risk factors associated with latent tuberculosis infection among healthcare workers in nampula central hospital, mozambique.201728595594
synthesis of 99mtc-rifabutin: a potential tuberculosis radiodiagnostic agent.rifabutin (rfn) is bactericidal antibiotic with a very broad spectrum of activity against gram positive & gram negative organisms including pseudomonas aeruginosa and specifically mycobacterium tuberculosis.201728595542
[resection of a tuberculous abscess of the thoracic wall].the patient was a 76-year-old man. chest computed tomography revealed an abscess of the chest wall incidentally. mycobacterium tuberculosis was detected by the aspiration of the abscess. since the abscess cavity exhibited a larger trend in spite of 3 months of antituberculosis chemotherapy, surgical resection was performed. during the operation, indigo stain was injected thorough an aspiration tube to visualize the spread of the abscess. the abscess was completely resected with combined partial ...201728595221
the introduction of mesenchymal stromal cells induces different immunological responses in the lungs of healthy and m. tuberculosis infected mice.mesenchymal stromal cells (msc) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. it was suggested recently that msc injections can be used to treat multi-drug resistant tuberculosis (tb). however, msc trafficking and immunomodulatory effects of msc injections during mycobacterium tuberculosis (mtb) infection have not been studied. to address this issue we have analyzed msc distribution in tissues and local immunological effects of msc i ...201728594940
structure-based optimization of pyridoxal 5'-phosphate-dependent transaminase enzyme (bioa) inhibitors that target biotin biosynthesis in mycobacterium tuberculosis.the pyridoxal 5'-phosphate (plp)-dependent transaminase bioa catalyzes the second step in the biosynthesis of biotin in mycobacterium tuberculosis (mtb) and is an essential enzyme for bacterial survival and persistence in vivo. a promising bioa inhibitor 6 containing an n-aryl, n'-benzoylpiperazine scaffold was previously identified by target-based whole-cell screening. here, we explore the structure-activity relationships (sar) through the design, synthesis, and biological evaluation of a syste ...201728594172
second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance mycobacterium tuberculosis peptides in human serum.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis (tb), the number one cause of death due to an infectious disease. tb diagnosis is performed by microscopy, culture or pcr amplification of bacterial dna, all of which require patient sputum or the biopsy of infected tissue. detection of mycobacterial products in serum, as biomarkers of diagnosis or disease status would provide an improvement over current methods. due to the low-abundance of mycobacterial products in serum, w ...201728592925
validation and implementation of clinical laboratory improvements act-compliant whole-genome sequencing in the public health microbiology laboratory.public health microbiology laboratories (phls) are on the cusp of unprecedented improvements in pathogen identification, antibiotic resistance detection, and outbreak investigation by using whole-genome sequencing (wgs). however, considerable challenges remain due to the lack of common standards. here, we describe the validation of wgs on the illumina platform for routine use in phls according to clinical laboratory improvements act (clia) guidelines for laboratory-developed tests (ldts). we dev ...201728592550
salt-regulated reversible fibrillation of mycobacterium tuberculosis isocitrate lyase: concurrent restoration of structure and activity.protein fibrillation is associated with a number of neurodegenerative diseases. nevertheless, several proteins not related to disease can also form fibrils in vitro under specific conditions. in the present study, we demonstrate the reversible fibrillation of a globular protein that is modulated by salt under physiological ph. mycobacterium tuberculosis isocitrate lyase (mtbicl) is a crucial enzyme involved in the glyoxylate shunt and a potential drug target against m. tuberculosis infection. un ...201728591590
detection of tuberculosis drug resistance: a comparison by mycobacterium tuberculosis mlpa assay versus genotype®mtbdrplus.to cope with the emergence of multidrug-resistant tuberculosis (mdr-tb), new molecular methods that can routinely be used to screen for a wide range of drug resistance related genetic markers in the mycobacterium tuberculosis genome are urgently needed.201728591399
epsp synthase flexibility is determinant to its function: computational molecular dynamics and metadynamics studies.flexibility is involved in a wide range of biological processes, such as protein assembly and binding recognition. epsp synthase is an enzyme that must undergo a large conformational change to accommodate its ligands into its binding cavity. however, although the structure of epsp synthase has been determined, its plasticity has not been explored in depth. therefore, in this work, we extensively examined the influence of the flexibility of mycobacterium tuberculosis epsp (mtepsp) synthase on the ...201728589464
latent tuberculosis infection and tuberculosis in patients with rheumatic diseases treated with anti-tumor necrosis factor agents.the introduction of biological agents, especially the tumor necrosis factor inhibitors (anti-tnf), for the treatment of rheumatic diseases increased the risk of developing tuberculosis (tb). screening for latent tb infection (ltbi) is strongly recommended before starting therapy with anti-tnf agents. the objective of this study was to identify the prevalence of ltbi and tb among patients with rheumatic diseases on anti-tnf agents. this is a cross-sectional study. the electronic medical records o ...201728589321
a case report on complicated tuberculous meningitis.tuberculous meningitis (tbm) is associated with significant complications of central nervous system. it is accompanied by nonspecific and heterogeneous clinical symptoms. we focused on the significance of early diagnosis and prompt treatment. we describe a case of tbm in a 19-year-old asian female. she had a progressive motor weakness with no sensory findings. she was started on antituberculous therapy. her magnetic resonance imaging (mri) contrast of dorsolumbar spine showed syringomyelia. her ...201728589071
identification and evaluation of the novel immunodominant antigen rv2351c from mycobacterium tuberculosis.there is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (tb) and the efficacy of the tb vaccine to control the disease worldwide. in this study, we evaluated the diagnostic potential of a novel mycobacterium tuberculosis (mtb)-specific antigen, rv2351c, from region of difference (rd) 7 of the mtb genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. twenty t-cell epitop ...201728588287
mycobacterium tuberculosis beijing genotype family strain isolated from naturally infected plateau zokor (myospalax baileyi) in china. 201728588286
optimisation of a murine splenocyte mycobacterial growth inhibition assay using virulent mycobacterium tuberculosis.in the absence of a validated correlate of protection or robust animal models for human tuberculosis, mycobacterial growth inhibition assays (mgias) aim to assess vaccines ability to inhibit mycobacterial growth in-vitro. we optimised a reproducible murine splenocyte mgia based on in-vitro infection with virulent mycobacterium tuberculosis (m.tb) erdman. we identified splenocyte viability as a problem in state-of-art mgia protocols, which can be improved by simple changes in culture conditions ...201728588268
clinical presentation of adult pulmonary tuberculosis (ptb): a study of 103 cases from a tertiary care hospital.tuberculosis, one of the oldest diseases known to affect humans, is a major cause of death worldwide. the disease, which is caused by the bacteria mycobacterium tuberculosis complex, usually affects the lungs, although other organs are involved in up to one-third of causes. if properly treated, tuberculosis caused by drug-susceptible strains is curable in virtually all cases. if untreated, the disease may be fatal within five years in 50-65% of cases. transmission usually takes place through the ...201728588156
mycobacterium tuberculosis rv3615c is a highly immunodominant antigen and specifically induces potent th1-type immune responses in tuberculosis pleurisy.t-cell responses have been demonstrated to be essential for preventing mycobacterium tuberculosis infection. the th1-cytokines produced by t cells, such as inf-γ, il-2, and tnf-α, not only limit the invasion of m. tuberculosis but also eliminate the pathogen at the site of infection. bacillus calmette-guérin (bcg) is known to induce th1-type responses but the protection is inadequate. identification of immunogenic components, in addition to those expressed in bcg, and induction of a broad spectr ...201728588103
evaluation of a novel line probe assay to detect resistance to pyrazinamide, a key drug used for tuberculosis treatment.the development of rapid molecular diagnostic assays for pyrazinamide (pza) resistance is considered technically challenging as mutations are highly diverse, scattered along the full length of the pnca gene and not all are associated with pza resistance. we evaluated the performance of the novel genoscholar pza-tb ii line probe assay (pza-lpa2; nipro corporation, japan).201728587904
identification and synthesis of novel inhibitors of mycobacterium atp synthase.a non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against m. smegmatis atp synthase. herein, we disclose our efforts to develop the structure activity relationship against mycobacterium tuberculosis (mtb.h37rv strain) around the identified hit 1. a scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against mtb.h37rv.201728587823
advances in drug discovery of new antitubercular multidrug-resistant compounds.tuberculosis (tb), a disease caused mainly by the mycobacterium tuberculosis (mtb), is according to the world health organization (who) the infectious disease responsible for the highest number of deaths worldwide. the increased number of multidrug-resistant (mdr-tb) and extensively drug-resistant (xdr-tb) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. the scenario of drug discovery becomes alarming when it ...201728587160
tea drinking and its association with active tuberculosis incidence among middle-aged and elderly adults: the singapore chinese health study.experimental studies showed that tea polyphenols may inhibit growth of mycobacterium tuberculosis. however, no prospective epidemiologic study has investigated tea drinking and the risk of active tuberculosis. we investigated this association in the singapore chinese health study, a prospective population-based cohort of 63,257 chinese aged 45-74 years recruited between 1993 and 1998 in singapore. information on habitual drinking of tea (including black and green tea) and coffee was collected vi ...201728587081
delayed and unreported drug-susceptibility testing results in the us national tuberculosis surveillance system, 1993-2014.drug-susceptibility testing (dst) of mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. dst is recommended for all culture-confirmed cases of tuberculosis. we examined trends in delayed and unreported dst results in the centers for disease control and prevention's national tuberculosis surveillance system.201728586626
clinical implications of new drugs and regimens for the treatment of drug-resistant tuberculosis.the emergence of drug-resistant tuberculosis (tb) is a growing problem worldwide. the lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. therefore, new tb drugs able to bolster the current tb treatment regimen are urgently required. novel drugs that are effective and safe against mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible tb and multi-dru ...201728584788
identification of novel efflux proteins rv0191, rv3756c, rv3008, and rv1667c involved in pyrazinamide resistance in mycobacterium tuberculosis.pyrazinamide (pza) is a critical drug used for the treatment of tuberculosis (tb). pza is a prodrug that requires conversion to the active component pyrazinoic acid (poa) by pyrazinamidase (pzase) encoded by the pnca gene. although resistance to pza is mostly caused by pnca mutations and less commonly by rpsa, pand, and clpc1 mutations, clinical strains without these mutations are known to exist. while efflux of poa was demonstrated in mycobacterium tuberculosis previously, the efflux proteins i ...201728584158
t cell-derived il-10 impairs host resistance to mycobacterium tuberculosis infection.tuberculosis (tb), caused by mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. cd4(+) t cells and several cytokines, such as the th1 cytokine ifn-γ, are critical in the control of this infection. conversely, the immunosuppressive cytokine il-10 has been shown to dampen th1 cell responses to m. tuberculosis infection impairing bacterial clearance. however, the critical cellular source of il-10 during m. tuberculosis infectio ...201728584007
tuberculosis arthritis of the sternoclavicular joint after uncomplicated falciparum malaria: a case report.malaria and tuberculosis are co-endemic in many developing countries. however their associations are rarely reported. yet, it has been suggested that a pathological process may link the two diseases.201728583115
qsar-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity.new anti-tuberculosis (anti-tb) drugs are urgently needed to battle drug-resistant mycobacterium tuberculosis strains and to shorten the current 6-12-month treatment regimen. in this work, we have continued the efforts to develop chalcone-based anti-tb compounds by using an in silico design and qsar-driven approach. initially, we developed sar rules and binary qsar models using literature data for targeted design of new heteroaryl chalcone compounds with anti-tb activity. using these models, we ...201728582669
aberrant plasma il-7 and soluble il-7 receptor levels indicate impaired t-cell response to il-7 in human tuberculosis.t-cell proliferation and generation of protective memory during chronic infections depend on interleukin-7 (il-7) availability and receptivity. regulation of il-7 receptor (il-7r) expression and signalling are key for il-7-modulated t-cell functions. aberrant expression of soluble (s) and membrane-associated (m) il-7r molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (aids) patients. here we investigated the role of il-7/il-7r on t ...201728582466
il17a augments autophagy in mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease.during mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. autophagy collaborates with human immune responses against mycobacterium tuberculosis (mt) in association with specific ifng secreted against the pathogen. however, ifng alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. actually, induction of th1 and th17 immune responses are required for protection ag ...201728581888
characteristics of drug resistant tuberculosis in sanatoria of north korea.although several reports about drug-resistant tuberculosis (tb) in north korea have been published, a nationwide surveillance on this disease remains to be performed. this study aims to analyze the drug resistance patterns of mycobacterium tuberculosis among the patients in the sanatoria of north korea, especially during the period when second-line drugs (slds) had not yet been officially supplied to this country. the eugene bell foundation (ebf) transferred 947 sputum specimens obtained from 66 ...201728581266
a single tube system for the detection of mycobacterium tuberculosis dna using gold nanoparticles based fret assay.the global combat against mtb is limited by challenges in accurate affordable detection. in this study, a rapid, affordable, single tube system for detection of unamplified mtb16s rdna was developed. utilizing a aunp based fret system, this assay achieved a sensitivity and specificity of 98.6% and 90% respectively.201728579440
construction of human masp-2-ccp1/2sp, ccp2sp, sp plasmid dna nanolipoplexes and the effects on tuberculosis in bcg-infected mice.the lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. the serine protease of masp-2 plays an essential role in complement activation of the lectin pathway. the c-terminal segment of masp-2 is comprised of the ccp1-ccp2-sp domains, and is the crucial catalytic segment. however, what is the effect of ccp1-ccp2-sp domains in controlling chronic infection is unknown. in order to evaluate the potential impact of ccp1-ccp2-sp domain ...201728578092
the synthesis and evaluation of triazolopyrimidines as anti-tubercular agents.we identified a di-substituted triazolopyrimidine with anti-tubercular activity against mycobacterium tuberculosis. three segments of the scaffold were examined rationally to establish a structure-activity relationship with the goal of improving potency and maintaining good physicochemical properties. a number of compounds displayed sub-micromolar activity against mycobacterium tuberculosis with no cytotoxicity against eukaryotic cells. non-substituted aromatic rings at c5 and a two-carbon chain ...201728576632
functional details of the mycobacterium tuberculosis vapbc26 toxin-antitoxin system based on a structural study: insights into unique binding and antibiotic peptides.toxin-antitoxin (ta) systems are essential for bacterial persistence under stressful conditions. in particular, mycobacterium tuberculosis express vapbc ta genes that encode the stable vapc toxin and the labile vapb antitoxin. under normal conditions, these proteins interact to form a non-toxic ta complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. here, we present the crystal structure of the m. tuberculosis vapbc26 complex and show that the ...201728575388
in vitro and in vivo activity of biapenem against drug-susceptible and rifampicin-resistant mycobacterium tuberculosis.biapenem, a carbapenem antibiotic, has been shown to have synergistic bactericidal anti-tb activity when combined with rifampicin both in vitro and in the mouse model of tb chemotherapy. we hypothesized that this synergy would result in biapenem/rifampicin activity against rifampicin-resistant mycobacterium tuberculosis .201728575382
the incremental value of repeated induced sputum and gastric aspirate samples for the diagnosis of pulmonary tuberculosis in young children with acute community-acquired pneumonia.mycobacterium tuberculosis (mtb) contributes to the pathogenesis of childhood acute community-acquired pneumonia in settings with a high tuberculosis burden. the incremental value of a repeated induced sputum (is) sample, compared with a single is or gastric aspirate (ga) sample, is not well known.201728575364
high rate of treatment completion in program settings with 12-dose weekly isoniazid and rifapentine (3hp) for latent mycobacterium tuberculosis infection.rcts demonstrated the newest ltbi regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3hp), as efficacious as 9 months of isoniazid (9h) with a greater completion rate (82% versus 69%); however, 3hp has not been assessed in routine health care settings.201728575208
genetic diversity & drug sensitivity profiles of mycobacterium tuberculosis isolates from two slums of jaipur city, rajasthan, india.slums are considered as hotspots of tuberculosis (tb). the study of genetic diversity and drug susceptibility profile of mycobacterium tuberculosis (mtb) will help understand the transmission dynamics and can be used for better prevention and control of the disease. the aim of this study was to determine the drug susceptibility profiles and genetic diversity using the random amplified polymorphic dna (rapd) and mycobacterial interspersed repetitive units-variable number of tandem repeats (miru v ...201728574018
line probe assay for detection of mycobacterium tuberculosis complex: an experience from central india.mycobacterium tuberculosis complex may sometimes not be detected in sputum samples of suspected multidrug-resistant tuberculosis (mdr-tb) patients by line probe assay (lpa) even though they are smear positive for acid-fast bacilli (afb). this retrospective analysis was attempted to understand and document our experience with lpa for detection of m. tuberculosis complex and diagnosis of mdr-tb under programmatic conditions.201728574017
the ser/thr protein kinase protein-protein interaction map of m. tuberculosis.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. there are 11 eukaryotic-like serine/threonine protein kinases (stpks) in mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. however, their underlying mechanisms of action remain largely uncharacterized. in this study, using a mtb proteome microarray, we have globally identified the binding proteins in mtb for all of the ...201728572091
individual- and neighborhood-level contextual factors are associated with mycobacterium tuberculosis transmission: genotypic clustering of cases in michigan, 2004-2012.using genotyping data of mycobacterium tuberculosis isolates from new cases reported to the tuberculosis (tb) surveillance program, we evaluated risk factors for recent tb transmission at both the individual- and neighborhood- levels among u.s.-born and foreign-born populations.201728571914
bioinformatics approach to prioritize known drugs towards repurposing for tuberculosis.new drugs are urgently needed to cure tuberculosis (tb) in a short period of time without causing any adverse effects since currently used drugs for the treatment of multi drug-resistant tb cause several adverse effects with poor success rate. therefore, we aimed to prioritize known drugs towards repurposing for tb by employing bioinformatics approach in the present study. a total of 1554 fda approved drugs were obtained from drugbank. serine/threonine-protein kinase, pknb (rv0014c) of mycobacte ...201728571806
determination and validation of a lower cut off value of cerebrospinal fluid adenosine deaminase (csf-ada) activity in diagnosis of tuberculous meningitis.tuberculous meningitis is an infection of the meninges caused by mycobacterium tuberculosis. it is one of the most common infectious diseases of the central nervous system (cns) and a major health problem in developing countries like india. if there is delay in diagnosis and initiation of specific treatment, it causes significant morbidity and mortality. csf-ada 10 u/l is the standard cut off value that is used for differentiation between tuberculous (tbm) and non-tuberculous meningitis (non-tbm ...201728571185
comparative diagnostic utility of is6110 pcr assay in csf and peripheral blood samples of tuberculous meningitis patients: a pilot study from central india.tuberculous meningitis (tbm) is the most severe form of central nervous system tuberculosis (cns-tb) and constitutes about 6% of all extrapulmonary tb (eptb) cases. most guidelines for the diagnosis and management of tbm agree on the use of simple cerebrospinal fluid (csf) analysis using molecular tools like polymerase chain reaction (pcr). however, the sensitivity of pcr varies while using a csf sample. in the present study, we have compared the diagnostic utility of pcr assay in both periphera ...201728571129
mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology.tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. we hypothesised that mycobacterium tuberculosis (mtb) specifically targets negative regulatory pathways to augment immunopathology. inhibition of signalling through the pi3k/akt/mtorc1 pathway increased matrix metalloproteinase-1 (mmp-1) gene expression and secr ...201728570642
the dynamics of immune responses to mycobacterium tuberculosis during different stages of natural infection: a longitudinal study among greenlanders.understanding human immunity to mycobacterium tuberculosis (mtb) during different stages of infection is important for development of an effective tuberculosis (tb) vaccine. we aimed to evaluate immunity to mtb infection by measuring immune responses to selected mtb antigens expressed during different stages of infection over time and to observe sustainability of immunity.201728570574
deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity.microorganisms are often studied as populations but the behaviour of single, individual cells can have important consequences. for example, tuberculosis, caused by the bacterial pathogen mycobacterium tuberculosis, requires months of antibiotic therapy even though the bulk of the bacterial population dies rapidly. shorter courses lead to high rates of relapse because subpopulations of bacilli can survive despite being genetically identical to those that are easily killed. in fact, mycobacteria c ...201728569798
diagnostic accuracy and usefulness of the genotype mtbdrplus assay in diagnosing multidrug-resistant tuberculosis in cameroon? a cross-sectional study.drug-resistant tuberculosis, especially multidrug-resistant tuberculosis (mdr-tb), is a major public health problem. effective management of mdr-tb relies on accurate and rapid diagnosis. in this study, we assessed the diagnostic accuracy of the genotype mtbdrplus assay in diagnosing mdr-tb in cameroon, and then discuss on its utility within the diagnostic algorithm for mdr-tb.201728569148
spatial-temporal distribution of genotyped tuberculosis cases in a county with active transmission.harris county, texas is the third most populous county in the united states and consistently has tuberculosis rates above the national average. understanding jurisdictional epidemiologic characteristics for the most common mycobacterium tuberculosis genotyped clusters is needed for tuberculosis prevention programs. our objective is to describe the demographic, laboratory, clinical, temporal and geospatial characteristics for the most common mycobacterium tuberculosis gentype clusters in harris c ...201728569145
serum enolase-2, high-sensitivity c-reactive protein, and serum cholesterol in smear-positive drug-naïve pulmonary tuberculosis.pulmonary tuberculosis (ptb) is a chronic granulomatous disease caused by mycobacterium tuberculosis. the present study determined the serum human enolase-2 (eno-2), high-sensitive c-reactive protein (hs-crp), and serum cholesterol levels as biological marker of disease activity and treatment response in smear-positive drug-naïve ptb.201728567068
[evaluation of quantiferon®-tb gold in tube test and tuberculin skin test in the diagnosis of mycobacterium tuberculosis infection].the aims of this study were to evaluate the sensitivity of quantiferon®-tb gold in tube (qft) test and its agreement with the tuberculin skin test (tst), to investigate possible factors associated with indeterminate qft test results and to explore the relationship between latent tuberculosis infection (ltbe) prevalence and the rate of tuberculosis (tb) cases in our region. 1455 cases with qft test performed in ege university faculty of medicine hospital between 2013 and 2015 were included in the ...201728566075
recombinant bacille calmette-guérin coexpressing ag85b-ifn-γ enhances the cell-mediated immunity in c57bl/6 mice.the only available vaccine against pulmonary tuberculosis is bacille calmette-guérin (bcg). as the efficacy reported of the vaccine is not up to the mark, there is an urgent need to develop improved anti-tuberculosis vaccines. antigen 85b (ag85b) is a very promising vaccine candidate molecule of mycobacterium tuberculosis and interferon (ifn)-γ and has been considered the most attractive correlate of protective immunity. the aim of this study was to construct a novel recombinant bcg (rbcg) to se ...201728565847
use of dna microarray chips for the rapid detection of mycobacterium tuberculosis resistance to rifampicin and isoniazid.the objective of the present study was to evaluate the potential development of dna microarray chips to detect rifampicin (rfp) and isoniazid (inh) resistance in mycobacterium tuberculosis (mtb), using samples from clinical tuberculosis (tb) patients in soochow city, china. the sputum samples of 42 patients with tb in the affiliated hospital of infectious diseases of soochow university (soochow, china) were collected. the conventional lowenstein-jensen culture medium (gold standard) was used to ...201728565846
development of an epitope panel for consistent identification of antigen-specific t-cells in humans.we aimed to establish a panel of mhc-peptide multimers suitable as a positive control in the detection of hla a*0201 restricted antigen specific t cells (astc) by flow cytometry. mhc dextramers were loaded with hla a*0201 binding peptides from viral antigens and melanoma targets identified from a literature search and in silico prediction. peripheral blood mononuclear cells (pbmc) from healthy donors were analysed with the mhc dextramers using flow cytometry. the best performing epitopes were te ...201728564390
new paradigm for translational modeling to predict long-term tuberculosis treatment response.disappointing results of recent tuberculosis chemotherapy trials suggest that knowledge gained from preclinical investigations was not utilized to maximal effect. a mouse-to-human translational pharmacokinetics (pks) - pharmacodynamics (pds) model built on a rich mouse database may improve clinical trial outcome predictions. the model included mycobacterium tuberculosis growth function in mice, adaptive immune response effect on bacterial growth, relationships among moxifloxacin, rifapentine, an ...201728561946
miliary tuberculosis with cerebral, liver, prostate and retroesophageal involvement.miliary tuberculosis results from the lymphohematogenous spread of mycobacterium tuberculosis and it is a rare form of this disease. the most affected places are the lymph nodes, pleura, and osteoarticular system, but any organ can be involved. currently the disease is still endemic in developing countries by its close association with poor living conditions and malnutrition. other comorbidities, particularly infection by human immunodeficiency virus (hiv), diabetes mellitus, smoking and alcohol ...201728560175
contribution of putative efflux pump genes to isoniazid resistance in clinical isolates of mycobacterium tuberculosis.isoniazid (inh) resistance in mycobacterium tuberculosis has been mainly attributed to mutations in katg (64%) and inha (19%). however, 20%-30% resistance to inh cannot be explained by mutations alone. hence, other mechanisms besides mutations may play a significant role in providing drug resistance. here, we explored the role of 24 putative efflux pump genes conferring inh-resistance in m. tuberculosis.201728559521
phenotypic low-level isoniazid resistance as a marker to predict ethionamide resistance in mycobacterium tuberculosis.tuberculosis is one of the most prevalent diseases in pakistan. pakistan has the highest burden of mdr-tb in the eastern mediterranean region. ethionamide is an anti-tuberculous drug frequently used to treat mdr-tb. its drug susceptibility testing is not easily available in resource limited settings. since it acts on the same target protein as isoniazid (inha protein encoded by inha gene), we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance.201728559519
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