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mycobacterium bovis bcg triggered myd88 induces mir-124 feedback negatively regulates immune response in alveolar epithelial cells.the emerging roles of micrornas (mirnas) and pulmonary epithelial cells in regulating the immune response against microbial invasion has attracted increasing attention in recent years, however, the immunoregulatory roles of mirnas in the pulmonary epithelial cells in response to mycobacterial infection has not been fully demonstrated. in this study, we show that mir-124 expression is induced upon mycobacterium bovis bacillus calmette-guerin (bcg) infection in a549 alveolar epithelial cells and m ...201424705038
evidence of increasing intra and inter-species transmission of mycobacterium bovis in south africa: are we losing the battle?tuberculosis caused by mycobacterium bovis is recognized worldwide as a significant health risk in domestic cattle, farmed and wild animal species as well as in humans. we carried out spoligotyping and variable number of tandem repeat (vntr) typing methods to characterize 490 m. bovis isolates from livestock (cattle, n=230; pig n=1) and wildlife species (n=259) originating from different farms and regions in south africa, with the aim to further establish the genetic diversity of the isolates, s ...201424703246
draft genome sequence of mycobacterium bovis strain an5, used for production of purified protein derivative.mycobacterium bovis strain an5 has been used to produce purified protein derivative (ppd) for the intradermal test for bovine tuberculosis since it was introduced in 1948. this work reports the draft genome sequence of m. bovis an5, which is used for the production of bovine ppd in brazil, as well as comparisons to other strains of m. bovis and mycobacterium tuberculosis.201424699964
polyclonal activation of naïve t cells by urease deficient-recombinant bcg that produced protein complex composed of heat shock protein 70, cyso and major membrane protein-ii.mycobacterium bovis bacillus calmette-guérin (bcg) is known to be only partially effective in inhibiting m. tuberculosis (mtb) multiplication in human. a new recombinant (r) urease-deficient bcg (bcg-dhcm) that secretes protein composed of heat shock protein (hsp)70, mtb-derived cyso and major membrane protein (mmp)-ii was produced for the efficient production of interferon gamma (ifn-γ) which is an essential element for mycobacteriocidal action and inhibition of neutrophil accumulation in lungs ...201424690183
feline mycobacterial infections.mycobacteria of feline importance include (1) obligate pathogens (tuberculosis), (2) mycobacteria that are difficult to grow, so the environmental niche is unknown (feline leprosy syndrome), and (3) facultative pathogenic opportunistic saprophytes (non-tuberculous mycobacteriosis). most cats present with cutaneous disease, although some have systemic involvement. diagnosis is challenging because there are no pathognomonic histopathological changes and many mycobacteria fail to culture, so molecu ...201424685470
local cattle movements in response to ongoing bovine tuberculosis zonation and regulations in michigan, usa.bovine tuberculosis (mycobacterium bovis) is an ongoing management issue in the state of michigan with eradication from livestock as the ultimate goal. eradication has been a challenge owing to the presence of a wildlife reservoir; competing interests in managing the livestock and wildlife hosts; and many uncertainties in transmission dynamics of m. bovis. one of the cornerstones of the eradication effort has been to stop movement of infected cattle among farms by imposing strict pre-movement te ...201424685049
defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer.low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (ta, t1, cis). however, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a heterogeneous group that does not fit into either of these categories. as a result, many urologists remain uncertain about the categorization of patients as intermediate risk as well as the selection of the most appro ...201424681333
strategic use of serology for the diagnosis of bovine tuberculosis after intradermal skin testing.diagnostic tests based on cell-mediated immunity are used in programmes for eradication of bovine tuberculosis (mycobacterium bovis). serological assays could be applied as ancillary methods to detect infected animals. our objective was to evaluate two serological techniques: m. bovis ab test (idexx, usa) and enferplex™ tb assay (enfer, ireland) in animals tested simultaneously with the single and comparative intradermal tests and the interferon-gamma assay. this work was performed at two stages ...201424679958
genotyping mycobacterium bovis from cattle in the central pampas of argentina: temporal and regional trends.mycobacterium bovis is the causative agent of bovine tuberculosis (tb), a disease that affects approximately 5% of argentinean cattle. among the molecular methods for genotyping, the most convenient are spoligotyping and variable number of tandem repeats (vntr). a total of 378 samples from bovines with visible lesions consistent with tb were collected at slaughterhouses in three provinces, yielding 265 m. bovis spoligotyped isolates, which were distributed into 35 spoligotypes. in addition, 197 ...201424676658
mycobacterium bovis infection in cats. 201424676264
unusual cluster of mycobacterium bovis infection in cats. 201424676263
feline tuberculosis caused by mycobacterium bovis. 201424676262
identification and survival studies of mycobacterium tuberculosis within laboratory-fermented bovine milk.mycobacterium tuberculosis and mycobacterium bovis are the classic agents causing tuberculosis (tb) in humans and animals respectively. transmission of tuberculous bacteria to humans usually occurs by inhalation of aerosols containing droplets of tubercle bacilli or via consumption of contaminated foods and drinks, primarily milk. the practice of milk pooling, including from cows with tb of the udder, further exacerbates the situation by rendering the whole milk supply infective. the simultaneou ...201424666844
a caspase-dependent pathway is involved in wnt/β-catenin signaling promoted apoptosis in bacillus calmette-guerin infected raw264.7 macrophages.apoptosis of alveolar macrophages following mycobacterium tuberculosis infection have been demonstrated to play a central role in the pathogenesis of tuberculosis. in the present study, we found that wnt/β-catenin signaling possesses the potential to promote macrophage apoptosis in response to mycobacterial infection. in agreement with other findings, an activation wnt/β-catenin signaling was observed in murine macrophage raw264.7 cells upon mycobacterium bovis bacillus calmette-guerin (bcg) inf ...201424663056
[genetic and immunologic determinants of intravesical bcg therapy in non-muscle-invasive urothelial bladder cancer].bladder cancer (bca) is one of the most common cancers. in 2010 in poland, 6296 people developed bladder cancer and 3110 people died of it. immunotherapy with bcg (bacillus calmette-guérin) is by far the most effective adjuvant therapy. noninfiltrating muscle membrane changes, that is, stages ta, tis and t1 qualify for bcg immunotherapy. bcg immunotherapy comprises series of bladder instillations, containing attenuated strain of mycobacterium bovis. the effectiveness of immunotherapy in non-inva ...201424662797
spatial predictors of bovine tuberculosis infection and brucella spp. exposure in pastoralist and agropastoralist livestock herds in the ruaha ecosystem of tanzania.while many studies investigate animal-related risk factors for disease, few have considered environmental or spatial risk factors in the dynamics of bovine tuberculosis (btb) and brucellosis. in the ruaha ecosystem of tanzania, we investigated the role of household location as a predictor for infection with mycobacterium bovis and exposure to brucella in pastoralist and agropastoralist cattle herds in a typical african wildlife-livestock-human interface. arcgis was utilized to calculate euclidia ...201424659301
investigation of a mycobacterium bovis outbreak in cattle at a colorado dairy in 2010.to describe an epidemiological investigation of a bovine tuberculosis outbreak on a colorado dairy operation.201424649991
the role of gamma delta t cells in immunity to mycobacterium bovis infection in cattle.accumulating evidence suggests that γδ t cells play a critical role in the early response to mycobacterium bovis and may be key in bridging innate and adaptive immunity following infection. in vitro, γδ t cells proliferate and produce robust amounts of ifnγ in response to complex, protein and non-protein mycobacterial antigens including m. bovis purified protein derivative (ppd), heat shock proteins and cell wall components such as mycolylarabinogalactan peptidoglycan (magp). vaccination with ba ...201424636303
relevance of bovine tuberculosis research to the understanding of human disease: historical perspectives, approaches, and immunologic mechanisms.pioneer studies on infectious disease and immunology by jenner, pasteur, koch, von behring, nocard, roux, and ehrlich forged a path for the dual-purpose with dual benefit approach, demonstrating a profound relevance of veterinary studies for biomedical applications. tuberculosis (tb), primarily due to mycobacterium tuberculosis in humans and mycobacterium bovis in cattle, is an exemplary model for the demonstration of this concept. early studies with cattle were instrumental in the development o ...201424636301
prevalence of bovine tuberculosis and risk factor assessment in cattle in rural livestock areas of govuro district in the southeast of mozambique.bovine tuberculosis (btb), caused by mycobacterium bovis, is an infectious disease of cattle that also affects other domestic animals, free-ranging and farmed wildlife, and also humans. in mozambique, scattered surveys have reported a wide variation of btb prevalence rates in cattle from different regions. due to direct economic repercussions on livestock and indirect consequences for human health and wildlife, knowing the prevalence rates of the disease is essential to define an effective contr ...201424632593
anti-mycobacterial activity of 1,3-diaryltriazenes.the rapid generation and spread of the drug resistant tuberculosis has led to an ongoing demand for novel compounds for therapeutic use. identification and study of compounds with the ability to inhibit mycobacterium tuberculosis is of paramount importance. for this reason, a library of substituted 1,3-diaryltriazenes based on the acting component of the anti-trypanosomal drug, diminazene aceturate was created and evaluated for its potential as anti-tubercular agent. several compounds were ident ...201424631899
overview and phylogeny of mycobacterium tuberculosis complex organisms: implications for diagnostics and legislation of bovine tuberculosis.members of the mycobacterium tuberculosis complex (mtbc) cause a serious disease with similar pathology, tuberculosis; in this review, bovine tuberculosis will be considered as disease caused by any member of the mtbc in bovids. bovine tuberculosis is responsible for significant economic loss due to costly eradication programs and trade limitations and poses a threat to both endangered and protected species as well as to public health. we here give an overview on all members of the mtbc, focusin ...201424630673
mycobacterium avium subsp. paratuberculosis antibody response, fecal shedding, and antibody cross-reactivity to mycobacterium bovis in m. avium subsp. paratuberculosis-infected cattle herds vaccinated against johne's disease.vaccination for johne's disease with killed inactivated vaccine in cattle herds has shown variable success. the vaccine delays the onset of disease but does not afford complete protection. johne's disease vaccination has also been reported to interfere with measurements of cell-mediated immune responses for the detection of bovine tuberculosis. temporal antibody responses and fecal shedding of mycobacterium avium subsp. paratuberculosis, the causative agent of johne's disease, were measured in 2 ...201424623626
detection of mycobacterium bovis in bovine and bubaline tissues using nested-pcr for tbd1.in the present study, a nested-pcr system, targeting the tbd1 region, involving the performance of conventional pcr followed by real-time pcr, was developed to detect mycobacterium bovis in bovine/bubaline tissue homogenates. the sensitivity and specificity of the reactions were assessed with dna samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other actinomycetales species and dna samples extracted directly from bovine and bubaline tissue homogenates. in terms of ...201424618787
hspx vaccination and role in virulence in the guinea pig model of tuberculosis.mycobacterium tuberculosis (mtb) currently infects billions of people; many of whom are latently infection and at risk for reactivation. mycobacterium bovis bacille calmette-guerin (bcg) while approved as a vaccine, is unable to prevent reactivation of latent tuberculosis infection (ltbi). subunit vaccines boosting bcg or given alone are being tested for efficacy in ltbi models. alpha-crystallin (acr, hspx), is a latency associated protein and subunit vaccine candidate. in this report, three hsp ...201424616427
[granulomatous pneumonia as a complication of intravesical bcg immunotherapy--a case report].bcg (bacillus calmette-guerin) comprises an attenuated strain of mycobacterium bovis and is used for vaccination against tuberculosis. an additional use of bcg is for immunotherapy of cancer in which the vaccine is administered intravesically for the treatment of superficial bladder cancer. the efficacy of immunotherapy with bcg in the prevention of recurrence is estimated at 70-99%, which is higher than for local chemotherapy. the most frequent complications of such treatment include fever and ...201424615200
topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (zno-nps) against human pathogens. zno-nps showed more activity against staphylococcus aureus and least against mycobacterium bovis-bcg. however, bcg killing was significantly increased in synergy with antituberculous-drug rifampicin. antibacterial mechanistic studies showed that zno-nps disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidati ...201424607937
physiological stress in the eurasian badger (meles meles): effects of host, disease and environment.a method for monitoring hypothalamic-pituitary-adrenal (hpa) responses of the eurasian badger (meles meles) to stressors was validated by measuring cortisol excretion in serum and faeces. serum and faecal samples were collected under anaesthesia from live-captured, wild badgers and fresh faeces was collected from latrines at 15 social groups in county down, northern ireland. variation in levels of cortisol in wild badgers was investigated relative to disease status, season, age, sex, body mass, ...201424607571
a wnt/β-catenin negative feedback loop represses tlr-triggered inflammatory responses in alveolar epithelial cells.increasing evidence has demonstrated that the epithelial cells in the lung play crucial roles in regulating certain inflammatory responses by modulating wnt signaling during microbial infection. however, the anti-microbial functions of wnt signaling in alveolar epithelial cells remain elusive. in this report, we show that wnt/β-catenin signaling is repressed in a549 alveolar epithelial cells during a toll-like receptor ligand stimulation with mycobacterium bovis bacillus calmette-guerin (bcg) or ...201424603120
evaluation of antibacterial and cytotoxic activity of artemisia nilagirica and murraya koenigii leaf extracts against mycobacteria and macrophages.artemisia nilagirica (asteraceae) and murraya koenigii (rutaceae) are widely distributed in eastern region of india. leaves of artemisia nilagirica plant are used to treat cold and cough by the local tribal population in east india. murraya koenigii is an edible plant previously reported to have an antibacterial activity. pathogenic strains of mycobacteria are resistant to most of the conventional antibiotics. therefore, it is imperative to identify novel antimycobacterial molecules to treat myc ...201424597853
mycobacteriosis in ostriches (struthio camelus) due to infection with mycobacterium bovis and mycobacterium avium complex.avian tuberculosis rarely affects ratites compared to other bird species and is typically caused by mycobacterium avium species. this study describes the pathological and microbiological findings in three adult ostriches with mycobacteriosis, in one of which mycobacterium bovis was isolated from the lesions. post mortem examinations on ostriches from two different zoological collections in ireland revealed multifocal caseous granulomas affecting the spleen and liver in all cases, with additional ...201324597127
linking bovine tuberculosis on cattle farms to white-tailed deer and environmental variables using bayesian hierarchical analysis.bovine tuberculosis is a bacterial disease caused by mycobacterium bovis in livestock and wildlife with hosts that include eurasian badgers (meles meles), brushtail possum (trichosurus vulpecula), and white-tailed deer (odocoileus virginianus). risk-assessment efforts in michigan have been initiated on farms to minimize interactions of cattle with wildlife hosts but research on m. bovis on cattle farms has not investigated the spatial context of disease epidemiology. to incorporate spatially exp ...201424595231
antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. paradoxically, we found that under nonpermissive growth conditions, exposure of mycobacterium bovis bcg bacilli to such antimicrobials enhanced their survival. we identified a transcriptional regulator, raas (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. induction of this transcriptional regulator re ...201424590482
assessment of mycobacterium bovis deleted in p27-p55 virulence operon as candidate vaccine against tuberculosis in animal models.a mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental vaccine in animal models. the mutant mbδp27-p55 was significantly more attenuated in nude mice than its parental strain but more virulent than bcg pasteur. challenge experiments in mice and guinea pigs using m. bovis or m. tuberculosis strains showed similar protection conferred by mbδp27-p55 mutant than bcg in terms of pathology and bacterial loads in spleen but lower protection than bcg in lungs. wh ...201424588000
a pilot study exploring the use of breath analysis to differentiate healthy cattle from cattle experimentally infected with mycobacterium bovis.bovine tuberculosis, caused by mycobacterium bovis, is a zoonotic disease of international public health importance. ante-mortem surveillance is essential for control; however, current surveillance tests are hampered by limitations affecting ease of use or quality of results. there is an emerging interest in human and veterinary medicine in diagnosing disease via identification of volatile organic compounds produced by pathogens and host-pathogen interactions. the objective of this pilot study w ...201424586655
effect of dose and route of immunisation on the immune response induced in cattle by heterologous bacille calmette-guerin priming and recombinant adenoviral vector boosting.bcg is used experimentally as a vaccine against tuberculosis (tb), induced by mycobacterium bovis, in cattle (btb). however, the efficacy of bcg is variable in humans, cattle and guinea pigs. an adenoviral vector expressing antigen 85a (ad5ag85a) has enhanced protection against tb in mice when used in combination with bcg for prime-boost experiments. however, the route of immunisation affects the degree of protection seen. this work examines the immunogenicity of a new vectored vaccine (ad5-tbf) ...201424581917
mycobacterium bovis ornithine carbamoyltransferase, mb1684, induces proinflammatory cytokine gene expression by activating nf-κb in macrophages.mycobacterium bovis is the etiological factor of bovine tuberculosis (btb), posing a significant problem to domestic cattle. the bacterium is also zoonotic, affecting human health worldwide. macrophage evasion of the bacterium involves mycobacterial molecules such as mb1684 (ornithine carbamoyltransferase). in this study, we confirmed a concentration-dependent decrease in proliferation of ana-1 macrophages when treated with rmb1684 when compared with mycobacterium bovis purified protein derivati ...201424568683
an etha-ethr-deficient mycobacterium bovis bcg mutant displays increased adherence to mammalian cells and greater persistence in vivo, which correlate with altered mycolic acid composition.tuberculosis remains a major worldwide epidemic because of its sole etiological agent, mycobacterium tuberculosis. ethionamide (eth) is one of the major antitubercular drugs used to treat infections with multidrug-resistant m. tuberculosis strains. eth is a prodrug that requires activation within the mycobacterial cell; its bioactivation involves the etha-ethr locus, which encodes the monooxygenase etha, while ethr is a transcriptional regulator that binds to the intergenic promoter region of th ...201424566628
inhibition of ifn-γ promotes anti-asthma effect of mycobacterium bovis bacillus calmette-guerin neonatal vaccination: a murine asthma model.the mycobacterium bovis bacillus calmette-guerin (bcg) neonatal vaccination inhibits allergy-induced pathologic changes. however, the mechanisms underlying this process are unclear. this study aimed to investigate the role of interferon (ifn)-γ and interleukin (il)-17 in the protective effects of the bcg neonatal vaccination on allergic pulmonary inflammation and airway hyperresponsiveness (ahr).201424560675
evaluation of antimicrobial and cytotoxic activities of plant extracts from southern minas gerais cerrado.the antimicrobial activity of plant hidroethanolic extracts on bacteria gram positive, gram negative, yeasts, mycobacterium tuberculosis h37 and mycobacterium bovis was evaluated by using the technique of agar diffusion and microdilution in broth. among the extracts evaluated by agar diffusion, the extract of bidens pilosa leaf presented the most expressive average of haloes of growth inhibition to the microorganisms, followed by the extract of b. pilosa flower, of eugenia pyriformis' leaf and s ...201424553603
association between caudal fold tuberculin test responses and results of an elisa for mycobacterium avium subsp paratuberculosis and mycobacterial culture of feces in tuberculosis-free dairy herds.objective--to evaluate associations between mycobacterium avium subsp paratuberculosis (map) and caudal fold tuberculin (cft) test results in cattle. design--longitudinal and cross-sectional evaluations. animals--1 california (approx 3,600 cows) and 3 colorado (approx 640, 1,190, and 1,480 cows) dairy herds considered free of mycobacterium bovis infection. procedures--in the california herd, the association between cft response and map status was determined with elisa and mycobacterial culture o ...201424548233
specific recognition of mycobacterial protein and peptide antigens by γδ t cell subsets following infection with virulent mycobacterium bovis.promoting effective immunity to mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. we report that γδ t cells from virulent m. bovis-infected cattle respond specifically and directly to complex, protein, and nonprotein mycobacterial ags. importantly, to our knowledge, we demonstrate for the first time that bovine γδ t cells specifically recognize peptide ags derived from the mycobacterial protein complex esat6:cfp10 and that this rec ...201424532582
new skin test for detection of bovine tuberculosis on the basis of antigen-displaying polyester inclusions produced by recombinant escherichia coli.the tuberculin skin test for diagnosing tuberculosis (tb) in cattle lacks specificity if animals are sensitized to environmental mycobacteria, as some antigens in purified protein derivative (ppd) prepared from mycobacterium bovis are present in nonpathogenic mycobacteria. three immunodominant tb antigens, esat6, cfp10, and rv3615c, are present in members of the pathogenic mycobacterium tuberculosis complex but absent from the majority of environmental mycobacteria. these tb antigens have the po ...201424532066
molecular profiling of mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme rv3378c.to identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent mycobacterium tuberculosis with the attenuated vaccine strain mycobacterium bovis bacillus calmette-guérin. comparative lipidomics analysis identified more than 1,000 molecular differences, including a previously unknown, mycobacterium tuberculosis-specific lipid that is composed of a diterpene unit linked to adenosine. we established the complete structure of the natural product as 1- ...201424516143
a tetr family transcriptional factor directly regulates the expression of a 3-methyladenine dna glycosylase and physically interacts with the enzyme to stimulate its base excision activity in mycobacterium bovis bcg.3-methyladenine dna glycosylase recognizes and excises a wide range of damaged bases and thus plays a critical role in base excision repair. however, knowledge on the regulation of dna glycosylase in prokaryotes and eukaryotes is limited. in this study, we successfully characterized a tetr family transcriptional factor from mycobacterium bovis bacillus calmette-guerin (bcg), namely bcg0878c, which directly regulates the expression of 3-methyladenine dna glycosylase (designated as mbaag) and infl ...201424509852
augmentation of antitubercular therapy with ifnγ in a patient with dominant partial ifnγ receptor 1 deficiency.osteomyelitis due to mycobacterium bovis bacille calmette-guerin (bcg) often develops in patients with interferon-γ receptor 1 (ifnγr1) deficiency. in these patients, susceptibility appears to be caused by impaired interleukin-12- and ifnγ-mediated immunity. here we report the case of a one-year-old girl with dominant partial ifnγr1 deficiency who suffered from lymphadenitis and multiple sites of osteomyelitis due to bcg infection. she was allergic to isoniazid and rifampicin--the prescribed sta ...201424509072
a proof of concept study to assess the potential of pcr testing to detect natural mycobacterium bovis infection in south american camelids.cases of mycobacterium bovis infection south american camelids have been increasing in great britain. current antemortem immunological tests have some limitations. cases at post mortem examination frequently show extensive pathology. the feasibility of detecting mycobacterium bovis dna in clinical samples was investigated.201424507471
pulmonary mycobacterium bovis bcg vaccination confers dose-dependent superior protection compared to that of subcutaneous vaccination.worldwide, the mycobacterium bovis bcg vaccine is one of the most widely used vaccines. however, it appears to be ineffective in preventing pulmonary tuberculosis. here, we show that pulmonary bcg vaccination of mice with a broad dose range provides superior protection against mycobacterium tuberculosis challenge compared to that of subcutaneous vaccination.201424501340
genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.tuberculosis (tb) caused by mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. there is significant heritability for host resistance to bovine tb (btb) in dairy cattle. to identify resistance loci for btb, we undertook a genome-wide association study in female holstein-friesian cattle with 592 cases and 559 age-matched controls from case herds. cases and controls were categorised into distinct phenotypes: sk ...201424496092
novel regimens identified in mice for treatment of latent tuberculosis infection in contacts of patients with multidrug-resistant tuberculosis.preventing the development of tuberculosis (tb) in contacts of patients with multidrug-resistant tb (mdr-tb) by the treatment of latent tb infection (ltbi) is highly desirable. however, few safe, well tolerated, and effective drugs are available to treat mdr-ltbi and the published guidance is limited. fortunately, six new chemical entities from four classes developed to treat tb have entered clinical trials in the past decade. we tested three of these drugs alone and in combination in an experim ...201424492372
mycobacteria bypass mucosal nf-kb signalling to induce an epithelial anti-inflammatory il-22 and il-10 response.the mechanisms by which mycobacteria subvert the inflammatory defence to establish chronic infection remain an unresolved question in the pathogenesis of tuberculosis. using primary epithelial cells, we have analysed mycobacteria induced epithelial signalling pathways from activation of tlrs to cytokine secretion. mycobacterium bovis bacilli calmette-guerin induced phosphorylation of glycogen synthase kinase (gsk)3 by pi3k-akt in the signalling pathway downstream of tlr2 and tlr4. mycobacteria d ...201424489729
comparison of antibody and cell-mediated immune responses of foals and adult horses after vaccination with live mycobacterium bovis bcg.equine neonates have reduced humoral and cell-mediated immune responses compared to adult horses after administration of killed vaccines. as a basis for this study, we hypothesized that newborn foals can mount strong immune responses after vaccination with live mycobacterium bovis bcg.201424486362
recombinant ag85b vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed mycobacteria-specific immune responses by intranasal immunization.viral vectors are promising vaccine candidates for eliciting suitable ag-specific immune response. since mycobacterium tuberculosis (mtb) normally enters hosts via the mucosal surface of the lung, the best defense against mtb is mucosal vaccines that are capable of inducing both systemic and mucosal immunity. although mycobacterium bovis bacille calmette-guérin is the only licensed tuberculosis (tb) vaccine, its efficacy against adult pulmonary forms of tb is variable. in this study, we assessed ...201424486310
modeling and mitigating winter hay bale damage by elk in a low prevalence bovine tuberculosis endemic zone.wildlife causes extensive crop damage throughout much of north america and these shared feeds are a key risk factor in the transmission of diseases between wildlife and livestock, including bovine tuberculosis (tb). predicting wildlife use of agricultural crops can provide insight directed toward targeted disease mitigation at areas of potential indirect interaction. in this study, we quantified use of hay bales by elk (cervus canadensis) during the winter in southwestern manitoba, canada using ...201424486094
asymmetric cell division in mycobacterium tuberculosis and its unique features.recently, several reports showed that about 80 % of mid-log phase mycobacterium smegmatis, mycobacterium marinum, and mycobacterium bovis bcg cells divide symmetrically with 5-10 % deviation in the septum position from the median. however, the mode of cell division of the pathogenic mycobacterial species, mycobacterium tuberculosis, remained unclear. therefore, in the present study, using electron microscopy, fluorescence microscopy of septum- and nucleoid-stained live and fixed cells, and live ...201424481536
multi-locus variable-number tandem repeat analysis (mlva) reveals heterogeneity of mycobacterium bovis strains and multiple genotype infections of cattle in ethiopia.bovine tuberculosis (btb) remains a major threat to animal and human health, and obstructs international and inter-regional livestock trade in ethiopia. many aspects of epidemiology of btb and its causative agent, mycobacterium bovis (m. bovis) are not well known. aims of the study were to elucidate molecular characteristics of m. bovis strains using mlva typing method. further aim was to determine infection pressure associated with occurrence of multiple genotypes in individual infected cattle. ...201424480051
circulating mycobacterium bovis peptides and host response proteins as biomarkers for unambiguous detection of subclinical infection.bovine tuberculosis remains one of the most damaging diseases to agriculture, and there is also a concern for human spillover. a critical need exists for rapid, thorough, and inexpensive diagnostic methods capable of detecting and differentiating mycobacterium bovis infection from other pathogenic and environmental mycobacteria at multiple surveillance levels. in a previous study, seth et al. (plos one 4:e5478, 2009, doi:10.1371/journal.pone.0005478) identified 32 host peptides that specifically ...201324478485
bacillus calmette-guerin cystitis after intravesical therapy. 201324470748
an immunomodulatory role for the mycobacterium tuberculosis region of difference 1 locus proteins pe35 (rv3872) and ppe68 (rv3873).the pathogenesis of mycobacterium tuberculosis involves the coordinate action of multiple bacillary components that modulate host immune responses to ensure its survival. one such group of factors is the multigenic pe_ppe protein family, several members of which have been implicated in host immune evasion. here we investigate the function of the pe-ppe gene pair pe35 (rv3872)-ppe68 (rv3873), located in the region of difference 1, encoding a specialized mycobacterial secretion system that is dele ...201424467650
tlr3 regulates mycobacterial rna-induced il-10 production through the pi3k/akt signaling pathway.cytokine induction in response to mycobacterium tuberculosis (mtb) infection is critical for pathogen control, by (i) mediating innate immune effector functions and (ii) instructing specific adaptive immunity. il-10 is an important anti-inflammatory cytokine involved in pathogenesis of tuberculosis (tb). here, we show that tlr3, a sensor of extracellular viral or host rna with stable stem structures derived from infected or damaged cells, is essential for mtb-induced il-10 production. upon mycob ...201424462705
analysis of mirna expression profiling in human macrophages responding to mycobacterium infection: induction of the immune regulator mir-146a.the regulatory mechanism of microrna (mirna) within macrophage innative response to mycobacterium tuberculosis infection is not clear yet.201424462562
phylogenetic polymorphisms in antibiotic resistance genes of the mycobacterium tuberculosis complex.sequence analysis of known antibiotic resistance genes of the mycobacterium tuberculosis complex (mtbc) is increasingly being used to infer phenotypic resistance to a variety of antibiotics. however, a clear understanding of the genotype-phenotype relationship is required to interpret genotypic susceptibility results accurately. in this context, it is particularly important to distinguish phylogenetically informative neutral polymorphisms from true resistance-conferring mutations.201424458512
evidence of presence of mycobacterium tuberculosis in bovine tissue samples by multiplex pcr: possible relevance to reverse zoonosis.bovine tuberculosis, caused by mycobacterium bovis, remains one of the most important zoonotic health concerns worldwide. the transmission of mycobacterium tuberculosis from humans to animals also occurs especially in countries where there is close interaction of humans with the animals. in the present study, thirty bovine lung tissue autopsy samples from an organized dairy farm located in north india were screened for the presence of mycobacterium tuberculosis complex by smear microscopy, histo ...201424456326
retrospective serological investigation of bovine tuberculosis in two gemsbok (oryx gazelle gazelle) and an onager (equus hemionus onager).in 1997 a 26-yr-old gemsbok (oryx gazelle gazelle) died of bovine tuberculosis in a zoo. three remaining gemsbok were administered the comparative tuberculin skin test repeatedly over a period of 5 mo. two animals showed inconclusive results on the second test. all three gemsbok were euthanatized. mycobacterium bovis was isolated from one of those with an inconclusive skin test result, whereas mycobacterium fortuitum was detected in the other gemsbok. eight years later, an onager (equus hemionus ...201324450065
retrospective study of morbidity and mortality of captive iberian lynx (lynx pardinus) in the ex situ conservation programme (2004-june 2010).medical records of 120 iberian lynx (lynx pardinus) from the captive breeding population (cbp), 96 of which were older than 1 wk old, were studied from january 2004 to june 2010. from a total of 413 clinical signs recorded, it was possible to obtain a diagnosis in 258 (62.5%). inappetence, skin wound, and vomiting had the highest incidence. adult (2 to 6 yr old) and juvenile (1 wk to 1 yr old) animals accounted for most of the clinical signs. vitamin d toxicosis and intraspecific trauma accounte ...201324450042
biological evaluation of diazene derivatives as anti-tubercular compounds.despite efforts made in chemotherapeutic research in the past and present, mycobacterium tuberculosis (m.tb), the etiological agent of tuberculosis, still causes more than a million deadly casualties each year, second only to hiv. the rapid generation and spread of drug resistant strains, a problem exacerbated by co-infection with hiv demands further efforts in the investigation of novel classes of anti-tubercular compounds. a library of eight substituted diazenecarboxamides, three carbamoyldiaz ...201424448419
myd88 signalling in myeloid cells is sufficient to prevent chronic mycobacterial infection.tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis that is responsible for almost 1.5 million deaths per year. sensing of mycobacteria by the host's immune system relies on different families of receptors present on innate immune cells. amongst them, several members of the tlr family are involved in the activation of immune cells by mycobacteria, yet the in vivo contribution of individual tlrs to the protective immune response remains controversial. on the contrary ...201424435955
mycobacterium bovis bcg infection severely delays trichuris muris expulsion and co-infection suppresses immune responsiveness to both pathogens.the global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. we investigated whether co-infection with the gastrointestinal tract-restricted helminth, trichuris muris, and the intracellular bacterium, mycobacterium bovis (m. bovis) bcg, would alter host immune responses to, or the pathological effect of, either infection.201424433309
long-term survival of tuberculosis complex mycobacteria in soil.while there is evidence for the persistence of mycobacterium bovis in soil, there are no reports for the other mycobacterium tuberculosis complex (mtc) mycobacteria. here, soil was inoculated with 10(8) c.f.u. g(-1) m. tuberculosis, m. bovis and m. canettii and subcultured monthly for 12 months. the pathogenicity of mycobacterial colonies, identified by using matrix-assisted laser desorption/ionization time of flight mass spectrometry, was assessed in a mouse model. moreover, mice were fed with ...201424425768
evaluating the tuberculosis hazard posed to cattle from wildlife across europe.tuberculosis (tb) caused by infection with mycobacterium bovis (m. bovis) and other closely related members of the m. tuberculosis complex (mtc) infects many domestic and wildlife species across europe. transmission from wildlife species to cattle complicates the control of disease in cattle. by determining the level of tb hazard for which a given wildlife species is responsible, the potential for transmission to the cattle population can be evaluated. we undertook a quantitative review of tb ha ...201424423727
physical characterization of synthetic phosphatidylinositol dimannosides and analogues in binary systems with phosphatidylcholine.native phosphatidylinositol mannosides (pims) from the cell wall of mycobacterium bovis (m. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. these activities have been investigated using particulate delivery systems containing native mannosylated lipids or total lipid extracts. limited work has been carried out examining the incorporation of individual pim lipids into suitable particulate formulations such as liposomes. the present study explored the pos ...201424423066
early detection of mycobacteria using a novel hydrogel culture method.early laboratory detection of mycobacterium tuberculosis is crucial for controlling tuberculosis. we developed a hydrogel mycobacterial culture method that retains the advantages of both solid and liquid methods in terms of speed, cost, and efficiency.201424422192
a novel synthetic mycolic acid inhibits bronchial hyperresponsiveness and allergic inflammation in a mouse model of asthma.recognition of microbes is important to trigger the innate immune system. mycolic acid (ma) is a component of the cell walls of mycobacteria such as mycobacterium bovis bacillus calmette-guerin. ma has immunogenic properties, which may modulate the innate and adaptive immune response. this study aimed to investigate whether a novel synthetic ma (sma) inhibits allergic inflammatory responses in a mouse model of asthma.201424404398
evaluation of the aid tb resistance line probe assay for rapid detection of genetic alterations associated with drug resistance in mycobacterium tuberculosis strains.the rapid accurate detection of drug resistance mutations in mycobacterium tuberculosis is essential for optimizing the treatment of tuberculosis and limiting the emergence and spread of drug-resistant strains. the tb resistance line probe assay from autoimmun diagnostika gmbh (aid) (strassburg, germany) was designed to detect the most prevalent mutations that confer resistance to isoniazid, rifampin, streptomycin, amikacin, capreomycin, fluoroquinolones, and ethambutol. this assay detected resi ...201424403306
association between spoligotype-vntr types and virulence of mycobacterium bovis in cattle.mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that affects approximately 5% of argentine cattle. the aim of this research was to study if it is possible to infer the degree of virulence of different m. bovis genotypes based on scorified observations of tuberculosis lesions in cattle. in this study, we performed association analyses between several parameters with tuberculosis lesions: m. bovis genotype, degree of progression of tuberculosis, and animal age. for thi ...201424398919
synthesis, cytostatic, antimicrobial, and anti-hcv activity of 6-substituted 7-(het)aryl-7-deazapurine ribonucleosides.a series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)aryl-7-deazaadenosine series. several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethy ...201424397620
bcg δzmp1 vaccine induces enhanced antigen specific immune responses in cattle.mycobacterium bovis (m. bovis) causes major economy and public health problem in numerous countries. in great britain, despite the use of a test-and-slaughter strategy, the incidence of bovine tuberculosis (btb) in cattle has steadily risen in recent years. one strategy being considered to reduce the burden of btb in cattle is the development of an efficient vaccine. the only current potentially available vaccine against tuberculosis, live attenuated m. bovis bacille calmette-guérin (bcg), has d ...201424394444
key role of effector memory cd4+ t lymphocytes in a short-incubation heparin-binding hemagglutinin gamma interferon release assay for the detection of latent tuberculosis.the treatment of latent tuberculosis infection (ltbi) in target populations is one of the current who strategies for preventing active tuberculosis (tb) infection and reducing the mycobacterium tuberculosis reservoir. therefore, powerful ltbi screening tools are indispensable. a gamma interferon release assay (igra) in response to the stimulation of peripheral blood mononuclear cells by the latency antigen native heparin-binding hemagglutinin (nhbha-igra) has proven its potential for this purpos ...201424391135
nanoparticulation of bcg-cws for application to bladder cancer therapy.the mycobacterium bovis bacille calmette-guerin cell wall skeleton (bcg-cws) could be used to replace live bcg as a bladder cancer drug. however, because bcg-cws is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. we report herein on the development of a novel packaging method that permits bcg-cws to be encapsulated into 166nm-sized lipid particles. the bcg-cws encapsulated nano particle (c ...201424389133
in vitro model of mycobacteria and hiv-1 co-infection for drug discovery.tuberculosis (tb) has become a global health threat in the wake of the human immunodeficiency virus (hiv) pandemic and is the leading cause of death in people with hiv/aids. treatment of patients with mycobacterium tuberculosis (mtb)/hiv co-infection is complicated by drug interactions and toxicity that present huge challenges for clinical intervention. discovery efforts to identify novel compounds with increased effectiveness and decreased drug-drug interactions against mtb, hiv-1, or both, wou ...201324388652
inhaled inactivated-mycobacterium phlei modulates γδt cell function and alleviates airway inflammation in a mouse model of asthma.mycobacterium bovis bacille calmette-guérin (bcg) and other mycobacterial infections suppress airway hyperresponsiveness and eosinophilic inflammation in asthma.γδt cells are important modulators of airway function and allergic inflammation. vγ1+γδt cells increase eosinophilic airway inflammation and airway hyperresponsiveness, while vγ4+γδt reduce airway hyperresponsiveness. the objective of this investigation was to determine the role of γδt cells and its subsets in the treatment of inhaled in ...201324383971
an assessment of zoonotic and production limiting pathogens in rusa deer (cervus timorensis rusa) from mauritius.a population of approximately 70,000 rusa deer (cervus timorensis russa) represents the most important mammal species reared for food on the island of mauritius, being the main source of red meat for the local population. however, very limited information is available on the circulation of pathogens affecting the productivity and health of this species. to produce baseline data on the circulation of infectious pathogens in rusa deer under production, a serological survey and/or direct pathogen d ...201424382104
extent of mycobacterium bovis infection in dairy cattle herds subject to partial culling as determined by an interferon-gamma assay.the interferon-gamma (ifn-γ) assay is employed as a complementary diagnostic test for bovine tuberculosis (btb) in many countries. to simplify this assay, we established a 96-well plate format using the esat-6 and cfp-10 antigens and then employed it to determine the extent of mycobacterium (m.) bovis infection in dairy herds with a history of btb outbreaks in a country where only selective culling is practiced. the sensitivity and specificity of this ifn-γ assay were 85.9% and 100%, respectivel ...201424378586
microrna-149 negatively regulates tlr-triggered inflammatory response in macrophages by targeting myd88.micrornas (mirnas) have been shown to be important regulators of tlr signaling pathway at the post-transcriptional level. in this study, the potential role of mir-149 was explored in murine alveolar macrophage raw264.7 cells. our results demonstrated a dynamic change of the expressions of mir-149 expression and myd88 in macrophage raw264.7 upon mycobacterium bovis bacillus calmette-guerlin (bcg) infection or lipopolysaccharide (lps) stimulation. the presence of bcg or lps dynamically reduced the ...201424375488
the role of glutamine oxoglutarate aminotransferase and glutamate dehydrogenase in nitrogen metabolism in mycobacterium bovis bcg.recent evidence suggests that the regulation of intracellular glutamate levels could play an important role in the ability of pathogenic slow-growing mycobacteria to grow in vivo. however, little is known about the in vitro requirement for the enzymes which catalyse glutamate production and degradation in the slow-growing mycobacteria, namely; glutamine oxoglutarate aminotransferase (gogat) and glutamate dehydrogenase (gdh), respectively. we report that allelic replacement of the mycobacterium b ...201324367660
binding pocket alterations in dihydrofolate synthase confer resistance to para-aminosalicylic acid in clinical isolates of mycobacterium tuberculosis.the mechanistic basis for the resistance of mycobacterium tuberculosis to para-aminosalicylic acid (pas), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. as a substrate analog of the folate precursor para-aminobenzoic acid, pas is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. as a result, the mutation of dihydrofolate synthase, an enz ...201424366731
current knowledge and pending challenges in zoonosis caused by mycobacterium bovis: a review.mycobacterium bovis is both the causative agent of bovine tuberculosis (tb) and a zoonotic pathogen. in humans, considerably fewer cases of tb are caused by m. bovis than m. tuberculosis; nevertheless, diagnostic limitations mean that currently available data on prevalence grossly underestimate the true dimension of the problem. the routes of transmission from animals to humans are well known and include direct exposure to infected animals or consumption of contaminated animal products. applicat ...201424360647
innate defects of the il-12/ifn-γ axis in susceptibility to infections by mycobacteria and salmonella.since 1996, several studies characterizing the association between primary immunodeficiencies and susceptibility to infections with environmental and non-pathogenic mycobacteria such as the bacillus calmette-guérin (mycobacterium bovis bacillus of calmette guérin strain) as well as disseminated infections by salmonella spp. have been conducted. these conditions, grouped in the so-called mendelian susceptibility to mycobacterial diseases, include a primary immunodeficiency caused by mutations in ...201424359575
targeting lipid esterases in mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (thl).tetrahydrolipstatin (thl) is bactericidal but its precise target spectrum is poorly characterized. here, we used a thl analog and activity-based protein profiling to identify target proteins after enrichment from whole cell lysates of mycobacterium bovis bacillus calmette-guérin cultured under replicating and non-replicating conditions. thl targets α/β-hydrolases, including many lipid esterases (lipd, g, h, i, m, n, o, v, w, and tesa). target protein concentrations and total esterase activity co ...201424345785
double recombinant mycobacterium bovis bcg strain for screening of primary and rationale-based antimycobacterial compounds.conventional antimycobacterial screening involves cfu analysis, which poses a great challenge due to slow growth of mycobacteria. recombinant strains carrying reporter genes under the influence of constitutive promoters allow rapid and wide screening of compounds but without revealing their modes of action. reporter strains using pathway-specific promoters provide a better alternative but allow a limited screening of compounds interfering with only a particular metabolic pathway. this reduces th ...201424342633
use of ethanol extract of mycobacterium bovis for detection of specific antibodies in sera of farmed red deer (cervus elaphus) with bovine tuberculosis.bovine tuberculosis (btb) in wildlife species poses a threat to domestic livestock in many situations. control programs for btb in livestock depend on testing and slaughtering the positive animals; however, the currently available diagnostic tests often have poor specificity. in our previous study, we developed a specific and sensitive enzyme linked immunosorbent assay (elisa) for another mycobacterial disease - johne's disease, using surface antigens of mycobacterium avium ssp. paratuberculosis ...201324341485
killed but metabolically active mycobacterium bovis bacillus calmette-guérin retains the antitumor ability of live bacillus calmette-guérin.mycobacterium bovis bacillus calmette-guérin is the most effective treatment for high risk noninvasive bladder cancer. although bacillus calmette-guérin immunotherapy clearly decreases recurrence and progression rates, side effects are common and infection with the bacillus has been described. for these reasons it is necessary to find safer alternatives to the live bacillus. we explored the possibility of using killed but metabolically active bacillus calmette-guérin.201424333111
the bcg moreau rd16 deletion inactivates a repressor reshaping transcription of an adjacent gene.the brazilian anti-tuberculosis vaccine strain mycobacterium bovis bacillus calmette-guérin (bcg) bcg moreau is unique in having a deletion of 7608 bp (rd16) that results in the truncation of a putative tetr transcriptional regulator, the ortholog of mycobacterium tuberculosis rv3405c, bcg_m3439c. we investigated the effect of this truncation on the expression of the rv3406 ortholog (bcg_m3440), lying 81 bp downstream in the opposite orientation. rt-pcr and western blot experiments show that rv3 ...201424332305
bovine tuberculosis risk factors for british herds before and after the 2001 foot-and-mouth epidemic: what have we learned from the tb99 and ccs2005 studies?over the last couple of decades, the uk experienced a substantial increase in the incidence and geographical spread of bovine tuberculosis (tb), in particular since the epidemic of foot-and-mouth disease (fmd) in 2001. the initiation of the randomized badger culling trial (rbct) in 1998 in south-west england provided an opportunity for an in-depth collection of questionnaire data (covering farming practices, herd management and husbandry, trading and wildlife activity) from herds having experien ...201524330476
targeting hunter distribution based on host resource selection and kill sites to manage disease risk.endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high-risk areas and individuals. we used resource selection functions (rsfs) and selection ratios (srs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed ...201324324876
a mycobacterial coinfection in a dog suspected on blood smear.a 4-year-old neutered female crossbred shepherd was referred for a history of 10 days of anorexia, polyuria, polydipsia, polyadenomegaly, and diarrhea. on physical examination, the dog appeared quiet, responsive, and apyretic, with generalized and severe lymphadenomegaly. hematologic abnormalities included neutrophilic leukocytosis with left shift, and lymphopenia. blood smears revealed intracytoplasmic bacilli negatively stained with may-grünwald-giemsa in neutrophils and monocytes. lymph node ...201324320783
immunization with a recombinant bacillus calmette-guerin strain confers protective th1 immunity against the human metapneumovirus.along with the human respiratory syncytial virus (hrsv), the human metapneumovirus (hmpv) is one of the leading causes of childhood hospitalization and a major health burden worldwide. unfortunately, owing to an inefficient immunological memory, hmpv infection provides limited immune protection against reinfection. furthermore, hmpv can induce an inadequate th2 type immune response that causes severe lung inflammation, leading to airway obstruction. similar to hrsv, it is likely that an effectiv ...201424319265
field evaluation of three blood-based assays for elk (cervus canadensis) naturally infected with mycobacterium bovis.diagnosis of mycobacterium bovis in wild populations is very challenging due to complications imposed by the use of traditional skin tests, poor sensitivity of gold standard tests which rely on culture of m. bovis from tissues and wide variations in severity of disease. various combinations of a lymphocyte stimulation test (lst), fluorescence polarization assay (fpa) and the cervid tb stat-pak were evaluated using two different validation approaches: a latent class analysis and classical statist ...201424315383
anti-mycobacterial activities of synthetic cationic α-helical peptides and their synergism with rifampicin.the rapid emergence of multi-drug resistant tuberculosis (tb) and the lack of effective therapies have prompted the development of compounds with novel mechanisms of action to tackle this growing public health concern. in this study, a series of synthetic cationic α-helical antimicrobial peptides (amps) modified with different hydrophobic amino acids was investigated for their anti-mycobacterial activity, both alone and in synergistic combinations with the frontline anti-tuberculosis drug rifamp ...201424314557
engrafted human cells generate adaptive immune responses to mycobacterium bovis bcg infection in humanized mice.currently used mouse models fail to fully reflect human immunity to tuberculosis (tb), which hampers progress in research and vaccine development. bone marrow-liver-thymus (blt) mice, generated by engrafting human fetal liver, thymus, and hematopoietic stem cells in severely immunodeficient nod/scid/il-2rγ(-/-) (nsg) mice, have shown potential to model human immunity to infection. we engrafted hla-a2-positive fetal tissues into nsg mice transgenically expressing human leukocyte antigen (hla)-a2. ...201324313934
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