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drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time.the current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. previously, using an output-driven optimization platform and an in vitro macrophage model of mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. here we use this platform to optimize the in vivo drug dose ...201728117835
phloretin exerts anti-tuberculosis activity and suppresses lung inflammation.an increase in the prevalence of the drug-resistant mycobacteria tuberculosis necessitates developing new types of anti-tuberculosis drugs. here, we found that phloretin, a naturally-occurring flavonoid, has anti-mycobacterial effects on h37rv, multi-drug-, and extensively drug-resistant clinical isolates, with minimum inhibitory concentrations of 182 and 364 μm, respectively. since mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of p ...201728117761
synthesis and biological activities of camphor hydrazone and imine derivatives.both sonochemical and classical methodologies have been employed to convert camphor, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one, c₉h16c=o, into a number of derivatives including hydrazones, c₉h16c=n-nhar 3, imines, c₉h16c=n-r 7, and the key intermediate nitroimine, c₉h16c=n-no₂ 6. reactions of nitroamine 6 with nucleophiles by classical methods provided the desired compounds in a range of yields. in evaluations of activity against mycobacterium tuberculosis, compound 7j exhibited the best activit ...201528117313
drug resistance mechanisms and novel drug targets for tuberculosis therapy.drug-resistant tuberculosis (tb) poses a significant challenge to the successful treatment and control of tb worldwide. resistance to anti-tb drugs has existed since the beginning of the chemotherapy era. new insights into the resistant mechanisms of anti-tb drugs have been provided. better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant tb. there is also a pressing need in the development of new drugs with novel targets ...201728117224
development of gallic acid formazans as novel enoyl acyl carrier protein reductase inhibitors for the treatment of tuberculosis.the enoyl acyl carrier protein reductase (inha) of mycobacterium tuberculosis (mtb) is an attractive target for developing novel antitubercular agents. a series of gallic acid formazans, were computationally designed and docked into the active site of inha to understand their binding mode and potential to inhibit inha. nine compounds from the designed series were identified as potential inha inhibitors, on the basis of good glide score. these compounds were synthesized in the laboratory and eval ...201728117201
synthesis, antimycobacterial and cytotoxic activity of α,β-unsaturated amides and 2,4-disubstituted oxazoline derivatives.the synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two mycobacterium tuberculosis strains (sensitive h37rv and a resistant clinical isolate) is reported. 2,4-disubstituted oxazolines (s)-3b,d,e were the most active in the sensitive strain with a mic of 14.2, 13.6 and 10.8μm, respectively, and the compounds (s)-3d,f were the most active against resistant strain with a mic of 6.8 and 7.4μm. the ex-vivo evaluation of hepatotoxi ...201728117200
evaluation of rapid genexpert mtb/rif method using dna tissue specimens of vertebral bones in patients with suspected spondylitis tb.to detect mycobacterium tuberculosis dna and rifampicin resistance in vertebral bone tissue specimens from spondylitis tb suspects.201728115796
characterization of t cells specific for cfp-10 and esat-6 in mycobacterium tuberculosis-infected mauritian cynomolgus macaques.nonhuman primates can be used to study host immune responses to mycobacterium tuberculosis mauritian cynomolgus macaques (mcms) are a unique group of animals that have limited major histocompatibility complex (mhc) genetic diversity, such that mhc-identical animals can be infected with m. tuberculosis two mcms homozygous for the relatively common m1 mhc haplotype were bronchoscopically infected with 41 cfu of the m. tuberculosis erdman strain. four other mcms, which had at least one copy of the ...201728115506
identification of mycobacterial rplj/l10 and rpsa/s1 proteins as novel targets for cd4(+) t cells.tuberculosis (tb) due to mycobacterium tuberculosis remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. we previously reported that a genetically modified strain of mycobacterium smegmatis called ikeplus is a promising tb vaccine candidate. since protective immunity induced by ikeplus is dependent on antigen-specific cd4(+) t cell memory, we hypothesized that the specificity of the ...201728115505
synergistic interactions of mmpl3 inhibitors with antitubercular compounds in vitro.a number of inhibitors of the essential mycobacterium tuberculosis mycolic acid transporter, mmpl3, are currently under development as potential novel antituberculosis agents. using the checkerboard method to study the interaction profiles of various antituberculosis drugs or experimental compounds with two different chemotypes inhibiting this transporter (indolcarboxamides and adamantyl ureas), we showed that mmpl3 inhibitors act synergistically with rifampin, bedaquiline, clofazimine, and β-la ...201728115355
close contact interferon-gamma response to the new psts1(285-374):cpf10: a preliminary 1-year follow-up study.the available diagnostic tools for latent tuberculosis (tb) infection (ltbi) via interferon-gamma (ifn-g) release assays (igra) are based on esat6:cfp10 stimulation. however, the mycobacterial antigen psts1 is also highly immunogenic and some of its fragments, such as psts1(285-374), have shown higher immunoreactivity in ltbi than in active tb. psts1(285-374), therefore, could increase the accuracy of the existing igra to detect ltbi. thus, a new chimeric protein has recently been developed (pst ...201728114976
identification of hpv types and mycobacterium tuberculosis complex in historical long-term preserved formalin fixed tissues in different human organs.university anatomical-pathological collections represent huge sources of human tissues and preparations from a variety of different diseases. with the help of modern genetic and histological methods, preserved fixed tissues from pathological collections can be used to re-evaluate former diagnoses. we analysed 25 specimens from our pathological collection with ages ranging from 78 to 112 years. the tissues originated from the oral cavity, lip, tongue, lung, bone, kidney, spleen, thymus, larynx, l ...201728114406
flavonoids from erythrina schliebenii.prenylated and o-methylflavonoids including one new pterocarpan (1), three new isoflavones (2-4), and nineteen known natural products (5-23) were isolated and identified from the root, stem bark, and leaf extracts of erythrina schliebenii. the crude extracts and their constituents were evaluated for antitubercular activity against mycobacterium tuberculosis (h37rv strain), showing mics of 32-64 μg ml(-1) and 36.9-101.8 μm, respectively. evaluation of their toxicity against the aggressive human b ...201728112509
polymerase chain reaction for mycobacterium tuberculosis dna detection from ocular fluids in patients with various types of choroiditis in a referral eye center in india.the aim of this study was to detect mycobacterium tuberculosis (mtb) dna with polymerase chain reaction (pcr) in aqueous or vitreous samples of patients suffering from choroiditis presumed to be infectious origin.201628112131
in silico approaches and chemical space of anti-p-type atpase compounds for discovering new antituberculous drugs.tuberculosis (tb) is one of the most important public health problems around the world. the emergence of multi-drug-resistant (mdr) and extensively drug-resistant (xdr) mycobacterium tuberculosis strains has driven the finding of alternative anti-tb targets. in this context, p-type atpases are interesting therapeutic targets due to their key role in ion homeostasis across the plasma membrane and the mycobacterial survival inside macrophages. in this review, in silico and experimental strategies ...201728111912
the effects of first-line anti-tuberculosis drugs on the actions of vitamin d in human macrophages.tuberculosis (tb) is a major global health problem. patients with tb have a high rate of vitamin d deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. although data on the efficacy of vitamin d supplementation on mycobacterium tuberculosis (mtb) clearance is uncertain from randomized controlled trials (rcts), vitamin d enhances the expression of the anti-microbial peptide human cathelicidin (hcap18) in cultured macrophages in vitro. one possible explana ...201628111615
quinolidene based monocarbonyl curcumin analogues as promising antimycobacterial agents: synthesis and molecular docking study.a series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [hdbu][hso4] as catalyst via knoevenagel type condensation and evaluated for their in vitro antitubercular activity against mycobacterium tuberculosis h37ra (mtb) and mycobacterium bovis bcg in dormant state. the analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. the antiproliferative activity of the analogues against mcf-7, a549 and hct-116 cell lines was evaluated using mo ...201728110868
multiplex pcr as a novel method in the diagnosis of spinal tuberculosis-a pilot study.establishment of a reliable and rapid diagnosis is of paramount importance in spinal tuberculosis. the available gadgetry of investigations, such as afb smear, culture of mycobacterium tuberculosis, and uniplex pcr, suffers from a lack of adequate sensitivity and/or a lack of rapidity. therefore, many times a diagnosis is made either very late in the disease process or sometimes empirical therapy has to be started because a definite diagnosis could not be made. all of these are not ideal situati ...201728110400
multidetector ct findings of histopathologically proven peritoneal tuberculous cold abscesses.to evaluate the characteristic multidetector ct findings of peritoneal tuberculous (tb) cold abscesses.201728110370
takayasu's arteritis with isolated pulmonary artery involvement in a middle-aged asian woman with hepatitis b and latent tuberculosis infection.we report a rare case of takayasu's arteritis with isolated pulmonary artery stenosis in the presence of active hepatitis b and latent mycobacterium tuberculosis infection in a middle-aged asian woman who initially presented with severe dyspnea on exertion and recurrent syncope, occasional burning chest pains, and fatigue. therapy of the active hepatitis b and latent m. tuberculosis infection together with a course of methotrexate led to a slight reversal of the symptoms, as angioplasty with or ...201728110338
performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in bamako, mali.in mali early detection and treatment of multidrug-resistant tuberculosis (mdr-tb) are still challenging due to the cost, time and/or complexity associated with regular tests. microscopic observation drug susceptibility (mods) is a low-cost assay validated by who in 2010. it is a liquid-culture-based assay to detect the 'cording' characteristic of mycobacterium tuberculosis complex and to assess susceptibility to both isoniazid and rifampicin defining multidrug-resistant tuberculosis (mdr-tb). i ...201728110049
the role of pattern recognition receptors in lung sarcoidosis.sarcoidosis is a granulomatous disorder of unknown etiology. infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. the etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. inflammation results from recognition of evolutionarily conserved structures of pathogens (pathogen-associated molecular patterns, pamps) and/or fro ...201728108375
conformational analysis of an antibacterial cyclodepsipeptide active against mycobacterium tuberculosis by a combined roe and rdc analysis.griselimycin (gm) and methylgriselimycin (mgm), naturally produced by microorganisms of the genus streptomyces, are cyclic depsipeptides composed of ten amino acids. they exhibit antibacterial activity against mycobacterium species by inhibiting the sliding clamp of prokaryotic dna polymerase iii and are therefore considered as potential anti-tuberculosis drugs. the difference between the peptides is the presence of l-(r)-4-methyl-proline in mgm instead of l-proline in gm at position 8 of the am ...201728106929
inhibition of innate immune cytosolic surveillance by an m. tuberculosis phosphodiesterase.mycobacterium tuberculosis infection leads to cytosolic release of the bacterial cyclic dinucleotide (cdn) c-di-amp and a host-generated cdn, cgamp, both of which trigger type i interferon (ifn) expression in a sting-dependent manner. here we report that m. tuberculosis has developed a mechanism to inhibit sting activation and the type i ifn response via the bacterial phosphodiesterase (pde) cdnp, which mediates hydrolysis of both bacterial-derived c-di-amp and host-derived cgamp. mutation of cd ...201728106876
naphthalimides selectively inhibit the activity of bacterial, replicative dna ligases and display bactericidal effects against tubercle bacilli.the dna ligases, enzymes that seal breaks in the backbones of dna, are essential for all organisms, however bacterial ligases essential for dna replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5'-triphosphate. this fact leads to the conclusion that nad⁺-dependent dna ligases in bacteria could be targeted by their co-factor specific inhibitors. the development of novel alternative medical strategies, i ...201728106753
early secreted antigenic target of 6-kda of mycobacterium tuberculosis stimulates il-6 production by macrophages through activation of stat3.as early secreted antigenic target of 6 kda (esat-6) of mycobacterium tuberculosis (mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied esat-6 stimulated il-6 production by macrophages. esat-6 stimulated significantly higher il-6 secretion by murine bone marrow derived macrophages (bmdm) compared to culture filtrate protein 10 kda (cfp10) and antigen 85a. polymyxin b, an lps blocker, did not affect esat-6 stimulated macrophage il ...201728106119
rhodococcus erythropolis as a host for expression, secretion and glycosylation of mycobacterium tuberculosis proteins.glycosylation is one of the most abundant posttranslational polypeptide chain modification in nature. although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of b cell epitopes, the role in t cell immunity is not completely understood. there is growing evidence about the importance of these modifications in host bacteria interactions in tuberculosis. it is known, that the sugars present in some mycobacterium tuberculosis glycoproteins ...201728103877
hybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: sar and docking studies.a number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against mycobacterium tuberculosis h37ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (mic 7.6-19.1 μg/ml, 12-35 μm) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (mic 23.4 μg/ml, 41 μm) as well as active (mic 25.4 μg/ml, 45 μm) stage. structural modifications of the compou ...201728103537
mycobacterium marinum degrades both triacylglycerols and phospholipids from its dictyostelium host to synthesise its own triacylglycerols and generate lipid inclusions.during a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (fas) and sterols are the major energy and carbon source for mycobacterium tuberculosis. mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. lipid droplets (lds) store fas in form of triacylglycerols (tags) and are energy reservoirs of prokaryotes and eukaryotes. using the dictyostelium discoideum/mycobacterium marinum infection m ...201728103313
effect of bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres on bone and joint tuberculosis in vitro.rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (rpms)-loaded bone-like hydroxyapatite/poly amino acid (bha/paa) is effective in curing staphylococcus aureus-induced chronic osteomyelitis. this study continues to investigate the effect of rpm-loaded bha/paa on the bacterial growth of mycobacterium tuberculosis (mtb), cell proliferation and differentiation in mtb h37rv-infected mg63 cells. furthermore, whether wnt/β-catenin signaling pathway was activated by rpm-loaded bha/paa was e ...201728102559
find tuberculosis strain bank: a resource for researchers and developers working on tests to detect mycobacterium tuberculosis and related drug resistance.the spread of multidrug-resistant (mdr) tuberculosis (tb) and extensively drug-resistant (xdr) tb hampers global efforts in the fight against tuberculosis. to enhance the development and evaluation of diagnostic tests quickly and efficiently, well-characterized strains and samples from drug-resistant tuberculosis patients are necessary. in this project, the foundation for innovative new diagnostics (find) has focused on the collection, characterization, and storage of such well-characterized ref ...201728100602
accuracy of line probe assays for the diagnosis of pulmonary and multidrug-resistant tuberculosis: a systematic review and meta-analysis.only 25% of multidrug-resistant tuberculosis (mdr-tb) cases are currently diagnosed. line probe assays (lpas) enable rapid drug-susceptibility testing for rifampicin (rif) and isoniazid (inh) resistance and mycobacterium tuberculosis detection. genotype mtbdrplusv1 was who-endorsed in 2008 but newer lpas have since been developed.this systematic review evaluated three lpas: hain genotype mtbdrplusv1, mtbdrplusv2 and nipro ntm+mdrtb. study quality was assessed with quadas-2. bivariate random-effe ...201728100546
antibodies to mycobacterium tuberculosis. 201728099836
transmission of extensively drug-resistant tuberculosis in south africa.background drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (hiv) infection worldwide. a widespread epidemic of extensively drug-resistant (xdr) tuberculosis is occurring in south africa, where cases have increased substantially since 2002. the factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. methods we conducted a prospective study involving 4 ...201728099825
thioridazine: a non-antibiotic drug highly effective, in combination with first line anti-tuberculosis drugs, against any form of antibiotic resistance of mycobacterium tuberculosis due to its multi-mechanisms of action.this review presents the evidence that supports the use of thioridazine (tz) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. the evidence consists of in vitro and ex vivo assays that demonstrate the activity of tz against all encountered mycobacterium tuberculosis (mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of mtb, or for human subjects infected w ...201728098814
the il-17a rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in argentina.mycobacterium tuberculosis (mtb) causes nearly 10 millions of new tuberculosis disease cases annually. however, most individuals exposed to mtb do not develop tuberculosis, suggesting the influence of a human genetic component. here, we investigated the association of the rs2275913 snp (g → a) from il-17a and tuberculosis in argentina by a case-control study. furthermore, we evaluated in vitro the functional relevance of this snp during the immune response of the host against mtb and analyzed it ...201728098168
bacterial subversion of camp signalling inhibits cathelicidin expression, which is required for innate resistance to mycobacterium tuberculosis.antimicrobial peptides such as cathelicidins are important components of innate immune defence against inhaled microorganisms, and have shown antimicrobial activity against mycobacterium tuberculosis in in vitro models. despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. we sought to determine whether the cathelicidin-related antimicrobial peptide gene (cramp), the murine functional homologue of the human cathelicidin gene (camp or ll-37 ...201728097645
thiazomycin, nocathiacin and analogs show strong activity against clinical strains of drug-resistant mycobacterium tuberculosis.thiazolyl peptides are a class of natural products with potent gram-positive antibacterial activities. lack of aqueous solubility precluded this class of compounds from advancing to clinical evaluations. nocathiacins and thiazomycins are sub-classes of thiazolyl peptides that are endowed with structural features amenable for chemical modifications. semi-synthetic modifications of nocathiacin led to a series of analogs with improved water solubility, while retaining potency and antibacterial spec ...201728096545
comprehensive essentiality analysis of the mycobacterium tuberculosis genome via saturating transposon mutagenesis.for decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. to date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. as a result, the e ...201728096490
loss-of-function mutations in hspr rescue the growth defect of a mycobacterium tuberculosis proteasome accessory factor e (pafe) mutant.mycobacterium tuberculosis uses a proteasome to degrade proteins by both atp-dependent and -independent pathways. while much has been learned about atp-dependent degradation, relatively little is understood about the atp-independent pathway, which is controlled by mycobacterium tuberculosisproteasome accessory factor e (pafe). recently, we found that a mycobacterium tuberculosispafe mutant has slowed growth in vitro and is sensitive to killing by heat stress. however, we did not know if these ph ...201728096448
resistance to thiacetazone derivatives active against mycobacterium abscessus involves mutations in the mmpl5 transcriptional repressor mab_4384.available chemotherapeutic options are very limited against mycobacterium abscessus, which imparts a particular challenge in the treatment of cystic fibrosis (cf) patients infected with this rapidly growing mycobacterium. new drugs are urgently needed against this emerging pathogen, but the discovery of active chemotypes has not been performed intensively. interestingly, however, the repurposing of thiacetazone (tac), a drug once used to treat tuberculosis, has increased following the decipherin ...201728096157
comparison of loop-mediated isothermal amplification assay and smear microscopy with culture for the diagnostic accuracy of tuberculosis.tuberculosis (tb) caused by mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. sputum smear microscopy remains the most widely available pulmonary tb diagnostic tool particularly in resource limited settings. a highly sensitive diagnostic with minimal infrastructure, cost and training is required. hence, we assessed the diagnostic performance of loop-mediated isothermal amplification (lamp) assay in detecting m.tuberculosis infection in sputum sa ...201728095790
esx-1 and phthiocerol dimycocerosates of mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis.although phthiocerol dimycocerosates (dim) are major virulence factors of mycobacterium tuberculosis (mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. localized in the outer membrane of mycobacterial pathogens, dim are predicted to interact with host cell membranes. interaction with eukaryotic membranes is a property shared with another virulence factor of mtb, the early secretory antigenic target esxa (also known as esat-6). this small protein, w ...201728095608
anti-tuberculosis activity and structure-activity relationships of oxygenated tricyclic carbazole alkaloids and synthetic derivatives.a series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of mycobacterium tuberculosis and a mammalian cell line (vero cells). from this series, twelve carbazoles showed a significant anti-tb activity. the four most active compounds were the naturally occurring carbazole alkaloids clauszoline-m (45), murrayaline-c (41), carbalexin-c (27), and the synthetic carbazole derivative 22 with mic90 values ranging from 1.5 to 3.7μm. the active compounds were ...201628094223
prevalence of latent tuberculosis infection among tuberculosis laboratory workers in iran.the risk of transmission of mycobacterium tuberculosis from patients to health care workers (hcws) is a neglected problem in many countries, including iran. the aim of this study was to estimate the prevalence of latent tuberculosis (tb) infection (ltbi) among tb laboratory staff in iran, and to elucidate the risk factors associated with ltbi.201728092930
genomic analysis of globally diverse mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.multidrug-resistant tuberculosis (mdr-tb), caused by drug-resistant strains of mycobacterium tuberculosis, is an increasingly serious problem worldwide. here we examined a data set of whole-genome sequences from 5,310 m. tuberculosis isolates from five continents. despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. we have identified harbin ...201728092681
ocular mycobacteriosis-dual infection of m. tuberculosis complex with m. fortuitum and m. bovis.we report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of mycobacterium tuberculosis complex with mycobacterium fortuitum and mycobacterium bovis in an immunosuppressed, non-hiv patient. we did a systematic review of literature on dual infection due to m. tuberculosis and m. fortuitum via medline and pubmed and could not find any case reported of causing this kind of dual infection in the eye.201728091937
evaluation of five serologic assays for bovine tuberculosis surveillance in domestic free-range pigs from southern spain.in countries where bovine tuberculosis (btb) is still prevalent the contact among different animal species in extensive systems contributes to the circulation of mycobacterium bovis (m. bovis) and other members of the mycobacterium tuberculosis complex (mtc). thus, free-range pigs can develop subclinical infections and may contribute to disease spread to bovine and wildlife. serodiagnosis has been proposed as a screening tool for detecting infected pig herds; however, the value of this method to ...201728089289
regulation of immunity to tuberculosis.immunity against mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. regulatory t (treg) cells express the transcription factor foxp3+ and constitute an essential counterbalance of inflammatory th1 responses and are required to maintain immune homeostasis. the first reports describing the presence of foxp3-expressing cd4+ treg cells in tuberculosis (tb) emerged in 2006. di ...201628087948
innate immune responses to tuberculosis.tuberculosis remains one of the greatest threats to human health. the causative bacterium, mycobacterium tuberculosis, is acquired by the respiratory route. it is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. however, m. tuberculosis bacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primar ...201628087945
laboratory diagnosis and susceptibility testing for mycobacterium tuberculosis.the laboratory, which utilizes some of the most sophisticated and rapidly changing technologies, plays a critical role in the diagnosis of tuberculosis. some of these tools are being employed in resource-challenged countries for the rapid detection and characterization of mycobacterium tuberculosis. foremost, the laboratory defines appropriate specimen criteria for optimal test performance. the direct detection of mycobacteria in the clinical specimen, predominantly done by acid-fast staining, m ...201628087944
the memory immune response to tuberculosis.immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. understanding long-term memory responses to mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (tb). for many years, triggering cd4 t cells and, in particular, those secreting interferon-γ has been the goal of most tb vaccine research, and numerous data from animals and humans sup ...201628087940
identification of unique essential proteins from a mycobacterium tuberculosis f15/lam4/kzn phage secretome library.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis disease (tb), the leading cause of death from bacterial infection worldwide. although treatable, the resurgence of multidrug-resistant and extensively drug-resistant tb is a major setback for the fight against tb globally. consequently, there is an urgent need for new mtb-derived biomarkers for use in the design of new drugs and rapid point-of-care diagnostic or prognostic tools for the management of tb transmission. therefo ...201728087649
engineering mycobacteria for the production of self-assembling biopolyesters displaying mycobacterial antigens for use as a tuberculosis vaccine.tuberculosis (tb) is a disease caused by mycobacterium tuberculosis or mycobacterium bovis and still remains one of the world's biggest global health burdens. recently, engineered polyhydroxyalkanoate (pha) biobeads that were produced in both escherichia coli and lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. we observed that such pha beads contained host cell proteins as impurities, which we hypothesized to have t ...201728087528
the impact of isgylation during mycobacterium tuberculosis infection in mice.mycobacterium tuberculosis infection results in 1.5 million deaths annually. type i interferon (ifn) signaling through its receptor ifnar correlates with increased severity of disease, although how this increases susceptibility to m. tuberculosis remains uncertain. isg15 is one of the most highly induced interferon stimulated genes (isgs) during m. tuberculosis infection. isg15 functions by conjugation to target proteins (isgylation), by noncovalent association with intracellular proteins, and b ...201728087453
[contribution of microbiology in the diagnosis of tuberculosis in castile and león (spain): findings of the grumicale 2013 study].a retrospective study was conducted by collecting microbiological tuberculosis (tb) data in castile and león during the year 2013 in order to determine the incidence and distribution of tb, and resistance to the tuberculostatic drug, and compare them with the epidemiological data provided by the department of epidemiological surveillance (sive).201728087144
evaluation of the xpert® mtb/rif assay and microscopy for the diagnosis of mycobacterium tuberculosis in namibia.tuberculosis (tb) kills approximately two million people and infects around nine million worldwide annually. its proper management, especially in resource-limited settings, has been hindered by the lack of rapid and easy-to-use diagnostic tests. sputum smear microscopy remains the cheapest, readily available diagnostic method but it only identifies less than half of the patients with a hiv/tb co-infection because the bacilli would have disseminated from the lungs to other areas of the body. the ...201728086955
dragmacidin g, a bioactive bis-indole alkaloid from a deep-water sponge of the genus spongosorites.a deep-water sponge of the genus spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin g. dragmacidin g was first reported by us in the patent literature and has recently been reported by hitora et al. from a sponge of the genus lipastrotheya. dragmacidin g is the first in this series of compounds to have a pyrazine ring linking the two indole rings. it also has a rare n-(2-mercaptoethyl)-guanidine side chain. dragmacidin g shows a broad spectrum of biological activity ...201728085024
the minimal unit of infection: mycobacterium tuberculosis in the macrophage.the interaction between mycobacterium tuberculosis and its host cell is highly complex and extremely intimate. were it not for the disease, one might regard this interaction at the cellular level as an almost symbiotic one. the metabolic activity and physiology of both cells are shaped by this coexistence. we believe that where this appreciation has greatest significance is in the field of drug discovery. evolution rewards efficiency, and recent data from many groups discussed in this review ind ...201628084213
diabetes and tuberculosis.the increase in type 2 diabetes mellitus (dm) patients in countries where tuberculosis (tb) is also endemic has led to the reemerging importance of dm as a risk factor for tb. dm causes a 3-fold increase in tb risk and a 2-fold increase in adverse tb treatment outcomes. given the sheer numbers of dm patients worldwide, there are now more tb patients with tb-dm comorbidity than tb-hiv coinfection. there is an urgent need to implement strategies for tb prevention and control among the millions of ...201628084206
tuberculous otomastoiditis.tuberculous otitis media and mastoiditis, or tuberculous otomastoiditis, is a rare but well-described infectious process occasionally affecting individuals in the united states but more frequently seen in countries where tuberculosis is endemic. infection may be primary and occur through mucus aspirated through the eustachian tube. alternatively, organisms may secondarily infect the nasopharynx when expectorated from the lungs and, less frequently, may be hematogenously spread. chronic otorrhea ...201628084203
mycobacterium bovis and other uncommon members of the mycobacterium tuberculosis complex.since its discovery by theobald smith, mycobacterium bovis has been a human pathogen closely related to animal disease. at present, m. bovis tuberculosis is still a problem of importance in many countries and is considered the main cause of zoonotic tuberculosis throughout the world. recent development of molecular epidemiological tools has helped us to improve our knowledge about transmission patterns of this organism, which causes a disease indistinguishable from that caused by mycobacterium t ...201628084202
the immune interaction between hiv-1 infection and mycobacterium tuberculosis.the modulation of tuberculosis (tb)-induced immunopathology caused by human immunodeficiency virus (hiv)-1 coinfection remains incompletely understood but underlies the change seen in the natural history, presentation, and prognosis of tb in such patients. the deleterious combination of these two pathogens has been dubbed a "deadly syndemic," with each favoring the replication of the other and thereby contributing to accelerated disease morbidity and mortality. hiv-1 is the best-recognized risk ...201628084192
synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents.resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a-5c) have been synthesized and screened for their antitubercular activity against mycobacterium tuberculosis h37ra (h37ra). the triazolethiones 4b and 4v showed high antitubercular activity (both mic and ic50 ) against the dormant h37ra by in vitro and ex vivo. they were ...201728083914
a case of koch's spine treated with modified transpedicular vertebral curettage and posterior fixation: a novel technique.tuberculosis (tb) is a chronic granulomatous infection caused by acid-fast mycobacterium tuberculosis bacilli. spinal involvement occurs in less than one percent of tb. spinal tb (pott's disease) accounts for 50% of skeletal tb. though it most commonly affects the thoracolumbar junction, it can occur at any level of the spine. early diagnosis and treatment is mandatory in order to avoid neurological complications and spinal deformity. we report a case of a young female with tuberculosis of d12-l ...201628083459
the wnt blows: on the functional role of wnt signaling in mycobacterium tuberculosis infection and beyond.in recent years, it has become apparent that the wnt signaling pathway, known for its essential functions in embryonic development and tissue homeostasis, exerts immunomodulatory functions during inflammation and infection. most functional studies indicate that wnt5a exerts pro-inflammatory functions on its cellular targets, which include various types of immune and non-immune cells. wnt5a expression has also been linked to the pathogenesis of chronic inflammatory diseases. activation of beta-ca ...201628082976
sub-optimal specificity of modified ziehl-neelsen staining for quick identification of tuberculous meningitis.background: microbiological confirmation of tuberculous meningitis (tbm) remains problematic. we assessed the diagnostic performance of a modified ziehl-neelsen (mzn) staining method that showed promise in earlier studies. methods: patients evaluated for tbm in shaanxi province, china, were prospectively enrolled from may, 2011 to april, 2013. cerebrospinal fluid (csf) specimens were evaluated using the xpert mtb/rif® assay, mzn staining, and standard biochemical and microbiological tests, toget ...201628082963
whole-genome sequences of mycobacterium tuberculosis tb282 and tb284, a widespread and a unique strain, respectively, identified in a previous study of tuberculosis transmission in central los angeles, california, usa.we report here the genome sequences of two mycobacterium tuberculosis clinical isolates previously identified in central los angeles, ca, in the 1990s using a pacbio platform. isolate tb282 represents a large-cluster strain that caused 27% of the tuberculosis cases, while tb284 represents a strain that caused disease in only one patient.201728082486
oligomeric state of hypoxanthine-guanine phosphoribosyltransferase from mycobacterium tuberculosis.sedimentation equilibrium and size-exclusion chromatography experiments on mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase (mthgprt) have established the existence of this enzyme as a reversibly associating mixture of dimeric and tetrameric species in 0.1 m tris-hcl-0.012 m mgcl2, ph 7.4. displacement of the equilibrium position towards the larger oligomer by phosphate signifies the probable existence of mthgprt as a tetramer in the biological environment. these data th ...201728082125
the bare essentials of antibiotic target validation.the convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. impdh was already identified an essential protein in mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. a new target appeared to be born. surprisingly, the two groups came to completely different conclusions about the vulnerability of impdh and its future as a drug target ...201728081610
structure-activity relationships of spectinamide antituberculosis agents: a dissection of ribosomal inhibition and native efflux avoidance contributions.spectinamides are a novel class of antitubercular agents with the potential to treat drug-resistant tuberculosis infections. their antitubercular activity is derived from both ribosomal affinity and their ability to overcome intrinsic efflux mediated by the mycobacterium tuberculosis rv1258c efflux pump. this study explores the structure-activity relationships through analysis of 50 targeted spectinamides. compounds are evaluated for ribosomal translational inhibition, mic activity in rv1258c ef ...201728081607
diagnostic accuracy of genexpert mtb/rif assay in comparison to conventional drug susceptibility testing method for the diagnosis of multidrug-resistant tuberculosis.xpert mtb/rif assay is regarded as a great achievement of modern medicine for the rapid diagnosis of multidrug-resistant tuberculosis (mdr-tb). the main purpose of this study was to determine the performance of xpert mtb/rif assay compared to conventional drug susceptibility testing (dst) method for the diagnosis of mdr-tb. a comparative cross sectional study was carried out at german-nepal tuberculosis project, kathmandu, nepal, from april 2014 to september 2014. a total of 88 culture positive ...201728081227
assessment of a 96-well plate assay of quantitative drug susceptibility testing for mycobacterium tuberculosis complex in china.to evaluate the performance of the sensitire mycotb mic plate (mycotb) which could measure the twelve anti-tuberculosis drugs susceptibility on one 96-wells plate.201728081169
isoniazid: a review of characteristics, properties and analytical methods.isoniazid is a synthetic antimicrobial and one of the most important first-line drugs used in the treatment of tuberculosis. since it was introduced in the therapy in 1952, the drug remains at the front line of the antituberculosis treatment mainly due to its potency and high selectivity against mycobacterium tuberculosis. pharmaceutical analysis and therapeutic drug monitoring of isoniazid in both, pharmaceuticals and biological samples, plays an important role to comprehend aspects regarding t ...201728080136
the quantiferon-tb gold in-tube assay in neuro-ophthalmology.although quantiferon-tb gold in-tube (qft-git) testing is regularly used to detect infection with mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (tb) has been questioned. the following is a cohort study analyzing the efficacy of qft-git testing as a method for detection of active tb disease in low-risk individuals in a neuro-ophthalmologic setting.201728079759
corrigendum: construction and application of a co-expression network in mycobacterium tuberculosis. 201728079164
[igra methods in the routine operation - quantiferon®-tb gold or t-spot.tb?]for indirect diagnosis of tuberculosis, two commercial igra (interferon gamma release assay) assays are available - primal quantiferon®-tb gold test, new version quantiferon®-tb gold plus test (four tube, differentiation in activity cd4+ a cd8+) and t-spot®.tb test. both methods are based on the same principle, but their workflows are different. in this article, both assays are compared on the collection of 284 patients. inter-rate agreement measure showed 81.3% consistency and cohens kappa inde ...201628078903
the role of uv radiation and vitamin d in the seasonality and outcomes of infectious disease.the seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. one of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (uvr), and its subsequent control of vitamin d production. here we show how uvr and vitamin d, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne ...201728078341
factors associated with missed detection of mycobacterium tuberculosis by automated bactec mgit 960 system.despite the demonstration of excellent performance, mycobacterial growth in bactec mgit 960 can go undetected. the aim of this study was to investigate the prevalence of "false-negative" culture sample in beijing and the potential factors associated with the detection failures by mgit 960. of the 577 sputum samples tested, 141 (24.4%) were culture-positive for mycobacteria, of which 133 (94.3%) were automatically determined by mgit 960 system and 8 (5.7%) were positive for visual growth (false n ...201628078294
il-37 confers protection against mycobacterial infection involving suppressing inflammation and modulating t cell activation.interleukin-37 (il-37), a novel member of the il-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (tb) has not been clearly elucidated. in this study, single nucleotide polymorphism (snp) analysis demonstrated an association of the genetic variant rs3811047 of il-37 with tb susceptibility. in line with previous report, a significant elevated il-37 abundance in the ...201728076390
biosynthesis of the methylthioxylose capping motif of lipoarabinomannan in mycobacterium tuberculosis.lipoarabinomannan (lam) is a lipoglycan found in abundant quantities in the cell envelope of all mycobacteria. the nonreducing arabinan termini of lam display species-specific structural microheterogeneity that impacts the biological activity of the entire molecule. mycobacterium tuberculosis, for instance, produces mannoside caps made of one to three α-(1 → 2)-manp-linked residues that may be further substituted with an α-(1 → 4)-linked methylthio-d-xylose (mtx) residue. while the biological fu ...201728075556
discovery of imidazo[1,2-a]pyridine ethers and squaramides as selective and potent inhibitors of mycobacterial adenosine triphosphate (atp) synthesis.the approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (atp) synthase as an attractive target to kill mycobacterium tuberculosis (mtb). herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (ipe) and squaramides (sqa) as inhibitors of mycobacterial atp synthesis. through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an atp synth ...201728075132
binding and processing of β-lactam antibiotics by the transpeptidase ldtmt2 from mycobacterium tuberculosis.β-lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as a therapeutic target. peptidoglycan stability in mycobacterium tuberculosis, especially during infection, relies on the nonconventional peptide cross-links formed by l,d-transpeptidases. these enzymes are known to be inhibited by β-lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active s ...201728075068
anti-folates potentiate bactericidal effects of other antimicrobial agents.synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. previously, vilchèze et al. found that, sulfamethoxazole (smx) could potentiate the bacterialcidal activity of isoniazid (inh) and rifampin (rif) in mycobacterium tuberculosis. to test if this was also the case in other bacteria, the ability to potentiate bactericidal effect of rif by smx was evaluated in escherichia coli, staphylococcus aureus, salmonella typhimurium and ...201728074051
dynamics of fluoroquinolones induced resistance in dna gyrase of mycobacterium tuberculosis.dna gyrase is a validated target of fluoroquinolones which are key components of multidrug resistance tuberculosis (tb) treatment. most frequent occurring mutations associated with high level of resistance to fluoroquinolone in clinical isolates of tb patients are a90v, d94g, and a90v-d94g (double mutant [dm]), present in the larger subunit of dna gyrase. in order to explicate the molecular mechanism of drug resistance corresponding to these mutations, molecular dynamics (md) and mechanics appro ...201728071975
the ppe2 protein of mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production.mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. it has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. here, we show that one of the unique ppe family member proteins of m. tuberculosis, ppe2, can limit nitric oxide (no) production by inhibiting inos gene transcription. ppe2 protein has a leucine zipper dna-binding motif and a functional n ...201728071726
design and construction of a cloning vector containing the hspx gene of mycobacterium tuberculosis.tuberculosis (tb) is a major cause of death worldwide. finding an effective vaccine against tb is the best way to control it. several vaccines against this disease have been developed but none are completely protective. the aim of this study was to design and construct a cloning vector containing the mycobacterium tuberculosis (m. tuberculosis) heat shock protein x (hspx).201628070534
spinal tuberculosis and cold abscess without known primary disease: case report and review of the literature.extrapulmonary tuberculosis (tb) is uncommon but not rare. bone and joint involvement constitute about 10% of extrapulmonary tb cases, with the spine being the most frequently affected site. spinal tb patients typically present with back pain but other constitutional or pulmonary symptoms may be absent, rendering the diagnosis difficult. this case explores challenges in the diagnosis of spinal tb. we report a case of a 39-year-old woman presenting with vague back swelling for many years. imaging ...201628070429
c-type lectin receptor dcir modulates immunity to tuberculosis by sustaining type i interferon signaling in dendritic cells.immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. tuberculosis (tb) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. here, we report that c-type lectin dendritic cell (dc) immunoreceptor (dcir), a key component in dc homeostasis, is required to modulate lung infl ...201728069953
interaction of the cd43 sialomucin with the mycobacterium tuberculosis cpn60.2 chaperonin leads to tumor necrosis factor alpha production.mycobacterium tuberculosis is the causal agent of tuberculosis. tumor necrosis factor alpha (tnf-α), transforming growth factor β (tgf-β), and gamma interferon (ifn-γ) secreted by activated macrophages and lymphocytes are considered essential to contain mycobacterium tuberculosis infection. the cd43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin cpn60.2, facilitating mycobacterium-macrophage contact. we report here that cpn60.2 induces b ...201728069816
mutation in an unannotated protein confers carbapenem resistance in mycobacterium tuberculosis.β-lactams are the most widely used antibacterials. among β-lactams, carbapenems are considered the last line of defense against recalcitrant infections. as recent developments have prompted consideration of carbapenems for treatment of drug-resistant tuberculosis, it is only a matter of time before mycobacterium tuberculosis strains resistant to these drugs will emerge. in the present study, we investigated the genetic basis that confers such resistance. to our surprise, instead of mutations in ...201728069655
antituberculosis compounds from a deep-sea-derived fungus aspergillus sp. scsio ind09f01.eleven diketopiperazine and fumiquinazoline alkaloids (1-11) together with a tetracyclic triterpenoid helvolic acid (12) were obtained from the cultures of a deep-sea derived fungus aspergillus sp. scsio ind09f01. the structures of these compounds (1-12) were determined mainly by the extensive nmr, esims spectra data and by comparison with previously described compounds. besides, anti-tuberculosis, cytotoxic, antibacterial, cox-2 inhibitory and antiviral activities of these compounds were evalua ...201728068839
prophage-mediated defence against viral attack and viral counter-defence.temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. mycobacteriophages are viruses that infect mycobacterial hosts including mycobacterium tuberculosis and mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. characterization of ten cluster n temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that ...201728067906
performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.tuberculosis (tb) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. serological tests have the potentially to impact tb diagnosis, in particular in extreme clinical settings.201628066611
targeting innate-like t cells in tuberculosis.peptide-specific conventional t cells have been major targets for designing most antimycobacterial vaccines. immune responses mediated by conventional t cells exhibit a delayed onset upon primary infection and are highly variable in different human populations. in contrast, innate-like t cells quickly respond to pathogens and display effector functions without undergoing extensive clonal expansion. specifically, the activation of innate-like t cells depends on the promiscuous interaction of high ...201628066410
functional studies of five toxin-antitoxin modules in mycobacterium tuberculosis h37rv.toxin-antitoxin (ta) systems, which consist of an intracellular toxin and its antidote (antitoxin), are encoded by ubiquitous genetic modules in prokaryotes. commonly, the activity of a toxin is inhibited by its antitoxin under normal growth conditions. however, antitoxins are degraded in response to environmental stress, and toxins liberated from antitoxins consequently induce cell death or growth arrest. in free-living prokaryotes, ta systems are often present in large numbers and are consider ...201628066388
a fluorescent probe for detecting mycobacterium tuberculosis and identifying genes critical for cell entry.the conventional method for quantitating mycobacterium tuberculosis (mtb) in vitro and in vivo relies on bacterial colony forming unit (cfu) enumeration on agar plates. due to the slow growth rate of mtb, it takes 3-6 weeks to observe visible colonies on agar plates. imaging technologies that are capable of quickly quantitating both active and dormant tubercle bacilli in vitro and in vivo would accelerate research toward the development of anti-tb chemotherapies and vaccines. we have developed a ...201628066347
synthesis, identification and in vitro biological evaluation of some novel quinoline incorporated 1,3-thiazinan-4-one derivatives.the present study describes the synthesis of two new series of 3-hydroxy-n-(4-oxo-2-phenyl-1,3-thiazinan-3-yl)-8-(trifluoromethyl)quinoline-2-carboxamide derivatives (4a-j) and 3-((7-chloroquinolin-4-ylamino)methyl)-2-phenyl-1,3-thiazinan-4-one derivatives (5a-7j). all the compounds were synthesized in moderate to good yield by one-pot three component cyclo-condensation reaction. the newly synthesized compounds were characterized by ft-ir, (1)h, (13)c nmr and elemental analysis. the compounds we ...201728065567
nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in south korea.nontuberculous mycobacteria (ntm) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (ra) patients. this study aimed to identify the incidence and clinical characteristics of ntm infection in ra patients living in tuberculosis (tb) infection endemic area.201728063416
disruption of redox catalytic functions of peroxiredoxin-thioredoxin complex in mycobacterium tuberculosis h37rv using small interface binding molecules.mycobacterium tuberculosis has distinctive ability to detoxify various microbicidal superoxides and hydroperoxides via a redox catalytic cycle involving thiol reductants of peroxiredoxin (prx) and thioredoxin (trx) systems which has conferred on it resistance against oxidative killing and survivability within host. we have used computational approach to disrupt catalytic functions of prx-trx complex which can possibly render the pathogen vulnerable to oxidative killing in the host. using protein ...201728063347
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