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development of a model to simulate infection dynamics of mycobacterium bovis in cattle herds in the united states.to develop a mathematical model to simulate infection dynamics of mycobacterium bovis in cattle herds in the united states and predict efficacy of the current national control strategy for tuberculosis in cattle.201323865885
adverse reactions related to treatment compliance during bcg maintenance therapy for non-muscle-invasive bladder cancer.the aim of the study was to investigate the factor of adverse reactions related to compliance with mycobacterium bovis bacillus calmette-guérin maintenance therapy in patients with high-risk non-muscle-invasive bladder cancer.201323858038
synthesis and antimycobacterial activity of analogues of the bioactive natural products sampangine and cleistopholine.identification and investigation of novel classes and compounds for the treatment of tuberculosis remains of utmost importance in the fight against the disease. despite many efforts, the weakly gram positive mycobacterium tuberculosis keeps demanding its toll in human lives. for this reason a small library of substituted and unsubstituted aza analogues of cleistopholine and sampangine were synthesized in a short and straightforward manner and tested in vitro against m.tb. the compounds showed pr ...201323850570
experimental aerosol mycobacterium bovis model of infection in goats.the use of animal models is essential in testing the efficacy for novel therapies against tuberculosis (tb). calves and non-human primates are examples of large animal models currently used to test tb vaccine efficacy but these animals are difficult and very expensive to house under high containment conditions. the goat may represent an effective but less expensive alternative for testing prototype vaccines against tb. goats are susceptible to mycobacterium bovis, mycobacterium caprae and mycoba ...201323850102
psts1 polymorphisms of mycobacterium tuberculosis strains may reflect ongoing immune evasion.the mycobacterial antigen psts1 is a highly immunogenic and immunostimulatory component of the mycobacterial cell membrane and a good candidate for the diagnosis and vaccination against tuberculosis. here we selected 180 clinical isolates of mycobacterium tuberculosis complex (mtbc) in china and 11 different bacille calmette guerin (bcg) strains, amplified the gene of the psts1 antigen and compared the sequences with those of four other mycobacterium bovis and bcg strains from the ncbi genome we ...201323849889
a review of tuberculosis at the wildlife-livestock-human interface in zambia.zambia's estimated incidence of all forms of human tuberculosis (tb) is 707/100,000. high prevalence of bovine tuberculosis (btb) - infection with mycobacterium bovis - in cattle and the kafue lechwe antelopes (kobus leche kafuensis) has been reported in the kafue basin. consumption of unpasteurised milk and meat products from infected animals poses a risk of transmitting zoonotic tuberculosis to people living at the human-animal interface. despite the reported high prevalence of btb in both liv ...201323849550
epidemiology of pyrazinamide-resistant tuberculosis in the united states, 1999-2009.pyrazinamide (pza) is essential in tuberculosis treatment. we describe the prevalence, trends, and predictors of pza resistance in mycobacterium tuberculosis complex (mtbc) in the united states.201323840002
mycobacterium tuberculosis rpfb drives th1-type t cell immunity via a tlr4-dependent activation of dendritic cells.the failure of mycobacterium bovis bcg as a tb vaccine against tb reactivation suggests that latency-associated proteins should be included in alternative tb vaccine development. further, antigens known to generate protective immunity against the strong th1 stimulatory response to reactivated tb should be included in novel vaccine design. recent studies have emphasized the importance of rpfs from mycobacterium tuberculosis in the reactivation process and cellular immunity. however, little is kno ...201323825389
human β-defensin 2 may inhibit internalisation of bacillus calmette-guérin (bcg) in bladder cancer cells.to investigate whether secretion of human β-defensin 2 (hbd-2) is induced by bacillus calmette-guérin (bcg) and to determine whether hbd-2 affects bcg internalisation in bladder cancer cells.201323819923
dormancy associated translation inhibitor (datin/rv0079) of mycobacterium tuberculosis interacts with tlr2 and induces proinflammatory cytokine expression.mycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one third of the world's population, mostly in a dormant state. the proteins encoded by the dormancy survival regulon (dosr regulon) are mainly responsible for survival of the bacilli in a latent form. to maintain latency, mycobacteria orchestrate a balanced interplay of different cytokines secreted by immune cells during the granulomatous stage. the function of most of the dosr regulon proteins of m. tu ...201323819907
evaluation of the performance of cellular and serological diagnostic tests for the diagnosis of tuberculosis in an alpaca (vicugna pacos) herd naturally infected with mycobacterium bovis.tuberculosis (tb) in llamas and alpacas has gained importance in recent years since they are imported into the european union mainly for serving as pets and for production of natural fibre. the intradermal tuberculin test has been widely used for diagnosis of tb in these species showing lack of sensitivity (se) although little information has been previously reported evaluating the effect on its performance of different ppd inoculation sites and time of readings. moreover, different cost-effecti ...201323809774
expression pattern of interferon-inducible transcriptional genes in neutrophils during bovine tuberculosis infection.mycobacterium bovis, the classical causative agent of bovine tuberculosis (btb), infects animals of agricultural importance and other mammals, including humans. neutrophils are one of the first lines of defense against all microbes and produce a diverse collection of antimicrobial molecules, which play an important role in the early control of tuberculosis progression. an interferon (ifn)-inducible neutrophil-driven blood transcriptional signature that consisted of both ifn-γ and type i ifn-α/β ...201323808561
a role for interleukin-17a in modulating intracellular survival of mycobacterium bovis bacillus calmette-guérin in murine macrophages.interleukin 17a il-17a is a crucial immunomodulator in various chronic immunological diseases including rheumatoid arthritis and inflammatory bowel disease. the cytokine has also been demonstrated to control the pathogenesis of the mycobacterium tuberculosis by dysregulating production of cytokines and chemokines and promoting granuloma formation. whether il-17a regulates innate defence mechanisms of macrophages in response to mycobacterial infection remains to be elucidated. in the current repo ...201323808492
reactivation of immune responses against mycobacterium tuberculosis by boosting with the cpg oligomer in aged mice primarily vaccinated with mycobacterium bovis bcg.mycobacterium bovis bacillus calmette guérin (bcg) vaccine, which has been inoculated to more than one billion people world-wide, has significant effect in preventing tuberculous meningitis and miliary tuberculosis (tb) in neonate and early childhood. however, bcg fails to adequately protect against pulmonary tb and reactivation of latent infections in adults. to overcome this problem, adequate booster is urgently desired in adult who received prior bcg vaccination, and appropriate animal models ...201323799936
novel phage display-derived mycolic acid-specific antibodies with potential for tuberculosis diagnosis.tuberculosis is a major cause of mortality and morbidity due to infectious disease. however, current clinical diagnostic methodologies such as pcr, sputum culture, or smear microscopy are not ideal. antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker. mycolic acid, which has been found in patient sputum samples and comprises a large portion of the mycobacterial cell wall, is an ideal target. however, generating anti-lipid antibodies using ...201323797850
single cell measurements of vacuolar rupture caused by intracellular pathogens.shigella flexneri are pathogenic bacteria that invade host cells entering into an endocytic vacuole. subsequently, the rupture of this membrane-enclosed compartment allows bacteria to move within the cytosol, proliferate and further invade neighboring cells. mycobacterium tuberculosis is phagocytosed by immune cells, and has recently been shown to rupture phagosomal membrane in macrophages. we developed a robust assay for tracking phagosomal membrane disruption after host cell entry of shigella ...201323792688
estimating the power of a mycobacterium bovis vaccine trial in irish badgers.the aim of this study was to estimate the power, using simulation techniques, of a group randomized vaccine field trial designed to assess the effect of vaccination on mycobacterium bovis transmission in badgers. the effects of sample size (recapture percentage), initial prevalence, sensitivity and specificity of the diagnostic test, transmission rate between unvaccinated badgers, vaccine efficacy for susceptibility (ves) and vaccine efficacy for infectiousness (vei), on study power were determi ...201323791123
tuberculosis patients co-infected with mycobacterium bovis and mycobacterium tuberculosis in an urban area of brazil.in this cross-sectional study, mycobacteria specimens from 189 tuberculosis (tb) patients living in an urban area in brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pnca gene and oxyr pseudogene analysis). of these samples, 174 isolates simultaneously grew on löwenstein-jensen (lj) and stonebrink (sb)-containing media and presented phenotypic and molecular profiles of mycobacterium tuberculosis, whereas 12 had molecular profiles of m. tuberculosis base ...201323778657
the intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria.nitric oxide (no) is a diffusible radical gas produced from the activity of nitric oxide synthase (nos). nos activity in murine macrophages has a protective role against mycobacteria through generation of reactive nitrogen intermediates (rnis). however, the production of no by human macrophages has remained unclear due to the lack of sensitive reagents to detect no directly. the purpose of this study was to investigate no production and the consequence to mycobacteria in primary human macrophage ...201323774601
mycobacterium bovis tenosynovitis.infectious tenosynovitis is a rare condition usually presenting with symptoms of joint pain, swelling and deformity. a large number of infectious organisms are known to cause tenosynovitis and prompt and accurate diagnosis is essential to ensure appropriate treatment is delivered before serious complications and functional impairment occurs. we report a case of mycobacterium bovis tenosynovitis, a rare cause of infectious tenosynovitis; we discuss the clinical features and management of this con ...201323771966
ruptured aortic aneurysm secondary to psoas abscess after intravesical bacilli calmette-guérin.bacillus calmette-guérin (bcg) is a live attenuated strain of mycobacterium bovis that has been used as effective treatment for early-stage transitional carcinoma of the urinary bladder. we present a case of a 68 year old man who had an abdominal aortic aneurysm following bcg therapy for bladder cancer. contrast enhanced computerized tomogram (cect) of abdomen and pelvis revealed bilateral hypodense lesions suggestive of psoas abscesses. in addition, a saccular abdominal aortic aneurysm measurin ...201223770877
mycobacterium bovis infection in a grey seal pup (halichoerus grypus). 201323764843
rifampin-resistant mycobacterium bovis bcg-induced disease in hiv-infected infant, vietnam. 201323764043
cellular immune responses to recombinant mycobacterium bovis bcg constructs expressing major antigens of region of difference 1 of mycobacterium tuberculosis.besides being the most widely used vaccine directed against tuberculosis (tb) worldwide, mycobacterium bovis bcg is also the most controversial vaccine in current use. its protective efficacy varies widely in different parts of the world. one approach to improving the current bcg vaccine might be to produce recombinant bcg strains that express major antigens encoded by genes that are present in the m. tuberculosis-specific region of difference 1 (rd1), such as pe35, cfp10, and esat6. in this stu ...201323761657
bovine tb in livestock and wildlife: what's in the genes?bovine tuberculosis (btb) is a chronic, infectious disease found in domestic livestock and wildlife. it is caused predominantly by mycobacterium bovis, which forms part of the mycobacterium tuberculosis complex. btb has serious implications for the movement of animals and animal products, biodiversity, and public health and is of significant economic concern. the existence of wildlife maintenance hosts makes it extremely difficult to eradicate btb, even when established control strategies are in ...201323757394
polyamines inhibit porin-mediated fluoroquinolone uptake in mycobacteria.polyamines decrease the permeability of the outer membrane of escherichia coli to fluoroquinolones and β-lactams. in this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in mycobacterium bovis bcg. our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. spermidine was most effective and demonstrated reversible dose- and ph-dependent inhibition ...201323755283
utility of 67ga scintigraphy in disseminated infection after bcg instillation for treatment of bladder carcinoma.intravesical instillations of bacille calmette-guérin (bcg), an attenuated live strain of mycobacterium bovis, is the treatment of choice for superficial bladder cancer. local side effects are frequent, although adverse systemic reactions are uncommon, but more serious. we present 2 patients who developed disseminated m. bovis infection with multiorgan involvement after intravesical bcg therapy. (67)ga scintigraphy was very helpful for the diagnosis as the only imaging tool with pathological fin ...201323751826
a single dose of a dna vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in mycobacterium bovis bcg-primed mice.mycobacterium bovis bcg prime dna (mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (tb) than bcg alone. this heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of tb infection control, especially in countries where tb is endemic. moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. the alanin ...201323740922
cell extract-containing medium for culture of intracellular fastidious bacteria.the culture of fastidious microorganisms is a critical step in infectious disease studies. as a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of coxiella burnetii. here, we demonstrate the exponential growth of several bacterial strains, including the c. burnetii nine mile phase i and phase ii strains, and c. burnetii isolates from humans and animals. low-oxygen-tension conditions and the presence of small ...201323740722
an effort to isolate mycobacterium bovis from environmental substrates during investigations of bovine tuberculosis transmission sites (cattle farms and wildlife areas) in michigan, usa.deer movements on cattle farms, wildlife feeding, and livestock management practices in michigan are thought to create opportunities for indirect transmission of mycobacterium bovis via environmental substrates. to confirm the presence of viable m. bovis in the environment, substrates were collected from 13 farms with culture-confirmed m. bovis in cattle and 5 sites with high prevalence of m. bovis in free-ranging deer. none of the samples processed for mycobacterial culture were positive for m. ...201123738108
zoonotic mycobacterium bovis-induced tuberculosis in humans.we aimed to estimate the global occurrence of zoonotic tuberculosis (tb) caused by mycobacterium bovis or m. caprae infections in humans by performing a multilingual, systematic review and analysis of relevant scientific literature of the last 2 decades. although information from many parts of the world was not available, data from 61 countries suggested a low global disease incidence. in regions outside africa included in this study, overall median proportions of zoonotic tb of ≤1.4% in connect ...201323735540
nitric oxide and klf4 protein epigenetically modify class ii transactivator to repress major histocompatibility complex ii expression during mycobacterium bovis bacillus calmette-guerin infection.pathogenic mycobacteria employ several immune evasion strategies such as inhibition of class ii transactivator (ciita) and mhc-ii expression, to survive and persist in host macrophages. however, precise roles for specific signaling components executing down-regulation of ciita/mhc-ii have not been adequately addressed. here, we demonstrate that mycobacterium bovis bacillus calmette-guérin (bcg)-mediated tlr2 signaling-induced inos/no expression is obligatory for the suppression of ifn-γ-induced ...201323733190
detection of mycobacterium bovis and mycobacterium tuberculosis from cattle: possible public health relevance.mycobacterium bovis and mycobacterium tuberculosis infect both animals and humans. the disease epidemiology by these agents differs in developed and developing countries due to the differences in the implementation of the prevention and control strategies. the present study describes the detection of m. bovis and m. tuberculosis from specimens of lungs and pulmonary lymph nodes of four cattle died in an organized herd of 183 cattle in the state of himachal pradesh, india, with inconclusive skin ...201123729897
detectability of bovine tb using the tuberculin skin test does not vary significantly according to pathogen genotype within northern ireland.strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. bovine tuberculosis (btb) is increasingly prevalent among farmed cattle in the uk, exerting a heavy economic burden on the farming industry and government. we aimed to determine whether strains of mycobacterium bovis (the causa ...201323712123
novel particulate vaccines utilizing polyester nanoparticles (bio-beads) for protection against mycobacterium bovis infection - a review.bovine tuberculosis (tb) continues to be a major health problem in cattle and development of a safe effective vaccine to control tb in cattle would be very useful. this paper reviews progress and provides new data in development of a tb bio-bead vaccine based on polyester nanoparticle inclusions which were produced by bioengineered bacteria. polyhydroxybutyrate (phb) biopolyester nanoparticles (bio-beads) have been produced which displayed mycobacterial antigens, ag85a and esat-6, on the surface ...201423707076
differential responses of macrophages from bovines naturally resistant or susceptible to mycobacterium bovis after classical and alternative activation.it is known that macrophages from naturally resistant animals possess a strong immune response against bovine tuberculosis to control mycobacterial infections. in the present study, the macrophage phagocytic activity, intracellular bacterial survival, and cytokine gene expression induced by classical and alternative activators against mycobacterium bovis in naturally resistant or susceptible bovines, were evaluated. animals were classified as naturally resistant or susceptible based on the capac ...201323707003
influenza a virus infection impairs mycobacteria-specific t cell responses and mycobacterial clearance in the lung during pulmonary coinfection.individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza a virus strains. we analyzed the impact of influenza a virus and mycobacterial respiratory coinfection on the development of cd8 t cell responses to each pathogen. coinfected mice exhibited reduced frequency and numbers of cd8 t cells specific to mycobacterium bovis bacille calmette-guérin (bcg) in the lun ...201323698750
gene polymorphisms in african buffalo associated with susceptibility to bovine tuberculosis infection.bovine tuberculosis (btb) is a chronic, highly infectious disease that affects humans, cattle and numerous species of wildlife. in developing countries such as south africa, the existence of extensive wildlife-human-livestock interfaces poses a significant risk of mycobacterium bovis transmission between these groups, and has far-reaching ecological, economic and public health impacts. the african buffalo (syncerus caffer), acts as a maintenance host for mycobacterium bovis, and maintains and tr ...201323691232
nitric oxide not apoptosis mediates differential killing of mycobacterium bovis in bovine macrophages.to identify the resistance phenotype against mycobacterium bovis in cattle, we used a bactericidal assay that has been considered a marker of this trait. three of 24 cows (12.5%) were phenotyped as resistant and 21 as susceptible. resistance of bovine macrophages (mφ) to bcg challenge was evaluated for its association with slc11a1 gt microsatellite polymorphisms within 3'utr region. twenty-three cows (95.8%) had a gt13 genotype, reported as resistant, consequently the slc11a1 polymorphism was no ...201323691050
poly(lactide-co-glycolide)-rifampicin nanoparticles efficiently clear mycobacterium bovis bcg infection in macrophages and remain membrane-bound in phago-lysosomes.nanoparticles (nps) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. the most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (plga) and has been extensively used in experiments aimed at delivering antibiotics against mycobacterium tuberculosis in animal models of tuberculosis. here, we describe fabrication of plga nps containing either a high concentration of rifampicin or d ...201323687375
stress-induced l-forms of mycobacterium bovis: a challenge to survivability.this study addressed the ability of mycobacterium bovis to produce unusual extreme morphologic forms (cell wall-deficient or l-forms) under stress conditions. models using nutrient starvation and cryogenic stress treatments of mycobacterium bovis, as well as the filtration technique followed by cultivation in semisolid medium, were used for isolation of l-form variants. morphological transformations and developmental stages, typical for the bacterial l-cycle were observed by electron microscopy. ...201323686122
tuberculosis transmission by mycobacterium bovis in a mixed cattle and goat herd.a tuberculosis (tb) outbreak caused by mycobacterium bovis occurred in a mixed herd of three cattle and eighteen goats in northern italy in 2005. all the cattle were removed, as opposed to the co-existing goats, who remained in the farm and were not subsequently tested by the official intradermal tuberculin test. at the beginning of may 2006, a 7-day old calf was introduced into the herd from an officially tb-free (otf) farm. on october 2006, tuberculous lesions were detected at the slaughterhou ...201323664181
mycobacterium bovis (bovine tuberculosis) infection in north american wildlife: current status and opportunities for mitigation of risks of further infection in wildlife populations.mycobacterium bovis (m. bovis), the causative agent of bovine tuberculosis, has been identified in nine geographically distinct wildlife populations in north america and hawaii and is endemic in at least three populations, including members of the bovidae, cervidae, and suidae families. the emergence of m. bovis in north american wildlife poses a serious and growing risk for livestock and human health and for the recreational hunting industry. experience in many countries, including the usa and ...201323657134
isocitrate lyase encoding plasmids in bcg cause increased survival in apob100-only ldlr-/- mice.we studied the role of isocitrate lyase in the interaction between mycobacterium bovis bcg and mice. apob100-only ldlr-/- (b6;129s-apobtm2sgyldlrtm1her/j) mice were inoculated with m. bovis bcg harbouring plasmids carrying the gene for isocitrate lyase. the presence of ~29 times more copies of this gene resulted in a higher bacterial yield in the spleens and lungs of the infected mice. the spleen was 3-4 times heavier, and in the spleen the bacteria survived over 10 days longer than did the bact ...201323653002
expression of non-replicating persistence associated genes of mycobacterium bovis in lymph nodes from skin test-reactor cattle.upon oxygen shift-down, mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called non-replicating persistence (nrp). during this phase, at least 48 genes, collectively named dormancy survival regulator (dosr) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. it remains unclear whether expression of nrp genes occurs within the ...201323651670
transition metal-α-amino acid complexes with antibiotic activity against mycobacterium spp.synthetic iridium-, rhodium-, and ruthenium-amino acid complexes with hydrophobic l-amino acids have antibiotic activity against mycobacterium spp., including mycobacterium bovis bcg and the rapidly growing species mycobacterium abscessus and mycobacterium chelonae. concentrations of transition metal-amino acid complexes demonstrating hemolysis or cytotoxicity were 10- to 25-fold higher than were the mics.201323650159
prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by mycobacterium bovis.human tuberculosis caused by m. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. the disease in humans is mainly attributed to unpasteurized dairy products consumption. however, transmission due to exposure of humans to infected animals has been also recognized. the prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (dfw ...201323638198
diminishing returns in bovine tuberculosis control.mycobacterium bovis causes bovine tuberculosis (btb) in many mammals including cattle, deer and brushtail possum. the aim of this study was to estimate the strength of association, using model selection (aicc) regression analyses, between the proportion of cattle and farmed deer herds with btb in new zealand and annual costs of tb control, namely disease control in livestock, in wildlife or in a combination of the two. there was more support for curved (concave up) than linear models which relat ...201323632097
mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, ethiopia.molecular typing of 964 specimens from patients in ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for m. bovis. we report a novel phylogenetic lineage of m. tuberculosis strongly associated with the horn of africa.201323622814
occurrence of mycobacteria in bovine milk samples from both individual and collective bulk tanks at farms and informal markets in the southeast region of sao paulo, brazil.mycobacterium spp. is one of the most important species of zoonotic pathogens that can be transmitted from cattle to humans. the presence of these opportunistic, pathogenic bacteria in bovine milk has emerged as a public-health concern, especially among individuals who consume raw milk and related dairy products. to address this concern, the brazilian control and eradication program focusing on bovine tuberculosis, was established in 2001. however, bovine tuberculosis continues to afflict approx ...201323618368
id-like reaction to bcg therapy for bladder cancer.id reaction, also known as autoeczematization, is the development of dermatitis that is distant to an initial site of infection or sensitization. clinical findings typically include an acute, intensely pruritic maculopapular or papulovesicular eruption that most frequently involves the extremities. histology typically reveals spongiotic dermatitis that often is vesicular, and eosinophils may be present in the infiltrate. id reactions can result from inflammatory skin conditions such as stasis de ...201323617086
analysis of the secretome and identification of novel constituents from culture filtrate of bacillus calmette-guerin using high-resolution mass spectrometry.tuberculosis (tb) is an infectious bacterial disease that causes morbidity and mortality, especially in developing countries. although its efficacy against tb has displayed a high degree of variability (0%-80%) in different trials, mycobacterium bovis bacillus calmette-guérin (bcg) has been recognized as an important weapon for preventing tb worldwide for over 80 years. because secreted proteins often play vital roles in the interaction between bacteria and host cells, the secretome of mycobacte ...201323616670
tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and n-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against mycobacterium tuberculosis targeting mmpl3.mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (tb). current treatment programs to combat tb are under threat due to the emergence of multi-drug and extensively-drug resistant tb. as part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (thpp) and n-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (spiro) analogues were recently ...201323613759
mycobacterium tuberculosis maltosyltransferase glge, a genetically validated antituberculosis target, is negatively regulated by ser/thr phosphorylation.glge is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against mycobacterium tuberculosis. despite also making α-glucan, the glgc/glga glycogen pathway is distinct and allosterically regulated. we have used a combination of genetics and biochemistry to establish how the glge pathway is regulated. m. tuberculosis glge was phosphorylated specifically by the ser/thr protein kinase pknb in vitro on one serine and ...201323609448
cd39 is involved in mediating suppression by mycobacterium bovis bcg-activated human cd8(+) cd39(+) regulatory t cells.regulatory t (treg) cells can balance normal tissue homeostasis by limiting inflammatory tissue damage, e.g. during pathogen infection, but on the other hand can also limit protective immunity induced during natural infection or following vaccination. because most studies have focused on the role of cd4(+) treg cells, relatively little is known about the phenotype and function of cd8(+) treg cells, particularly in infectious diseases. here, we describe for the first time the expression of cd39 ( ...201323606272
spatial relationships between eurasian badgers (meles meles) and cattle infected with mycobacterium bovis in northern spain.recent studies suggest that badgers may be a potential reservoir of mycobacterium bovis infection for cattle in northern spain. the objective of this study was to investigate potential epidemiological links between cattle and badgers. culture and molecular typing data were available for cattle culled during the national tuberculosis (tb) eradication campaigns between 2008 and 2012, as well as from 171 necropsied badgers and 60 live animals trapped and examined over the same time period. mycobact ...201323602422
tuberculosis infection in wildlife from the ruaha ecosystem tanzania: implications for wildlife, domestic animals, and human health.mycobacterium bovis, a pathogen of conservation, livestock, and public health concern, was detected in eight species of wildlife inhabiting protected areas bordering endemic livestock grazing lands. we tested tissues from 179 opportunistically sampled hunter-killed, depredation, road-killed, and live-captured wild animals, representing 30 species, in and adjacent to ruaha national park in south-central tanzania. tissue culture and pcr were used to detect 12 (8.1%) m. bovis-infected animals and 1 ...201323601163
rapid detection of serum antibody by dual-path platform vettb assay in white-tailed deer infected with mycobacterium bovis.bovine tuberculosis (tb) in cervids remains a significant problem affecting farmed herds and wild populations. traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. the recently developed immunochromatographic dual-path platform (dpp) vettb assay has two antigen bands, t1 (mpb83 protein) and t2 (cfp10/esat-6 fusion protein), for antibody detection. we evaluated the diagnostic accuracy of this test by usin ...201323595504
adaptation of mycobacteria to growth conditions: a theoretical analysis of changes in gene expression revealed by microarrays.microarray analysis is a powerful technique for investigating changes in gene expression. currently, results (r-values) are interpreted empirically as either unchanged or up- or down-regulated. we now present a mathematical framework, which relates r-values to the macromolecular properties of population-average cells. the theory is illustrated by the analysis of published data for two species; namely, mycobacterium bovis bcg pasteur and mycobacterium smegmatis mc(2) 155. each species was grown i ...201323593152
a review of bovine tuberculosis at the wildlife-livestock-human interface in sub-saharan africa.infection of wild animals by bovine tuberculosis (btb) is raising concern worldwide. this article reviews the current epidemiological situation, risk of emergence and control options at the wildlife–livestock–human interface in sub-saharan africa. in livestock, btb has been confirmed in the majority of countries from all parts of the continent. wildlife infection is confirmed in seven countries from southern and eastern africa, apparently spreading in the southern africa region. mycobacterium bo ...201323587372
pre-treatment with mycobacterium avium-derived lipids reduces the macrophage response to interferon γ in bcg-vaccinated mice.mycobacterium bovis bacille calmette-guérin (bcg) is the current vaccine used against mycobacterium tuberculosis (mtb) infection. however, exposure to environmental pathogens, such as mycobacterium avium, interferes with the immune response induced by bcg vaccination. how m. avium affects the efficiency of bcg is unclear. in this study, bcg-vaccinated mice pre-treated with m. avium-derived lipids (mals) showed a higher mycobacterial load and increased infiltration of inflammatory cells compared ...201323579397
comparison of the mgit 960, bactec 460 tb and solid media for isolation of mycobacterium bovis in united states veterinary specimens.bacteriologic culture remains one of the most important methods to diagnose bovine tuberculosis despite the lengthy incubation time, significant decontamination and media expense, and high biocontainment requirements. media selection is an important determination of culture sensitivity, and the planned discontinuation of the bactec 460 tb culture system has challenged veterinary diagnostic laboratories to evaluate alternatives. at the national veterinary services laboratories the bactec mgit 960 ...201323578209
overexpression of the kdpf membrane peptide in mycobacterium bovis bcg results in reduced intramacrophage growth and altered cording morphology.membrane peptides appear as an emerging class of regulatory molecules in bacteria, which can interact with membrane proteins, such as sensor kinases. to date, regulatory membrane peptides have been completely overlooked in mycobacteria. the 30 amino-acid-long kdpf peptide, which is co-transcribed with kdpabc genes and regulated by the kdpde two-component system, is supposed to stabilize the kdpabc potassium transporter complex but may also exhibit unsuspected regulatory function(s) towards the k ...201323577107
fever of unknown origin and pancytopenia caused by culture-proven delayed onset disseminated bacillus calmette-guerin (bcg) infection after intravesical instillation.a 78-year-old man was diagnosed with bladder carcinoma in situ and was successfully treated with intravesical bacillus calmette-guérin (bcg) instillations. at 6 months after the last dose, he developed fever, weight loss and malaise. he had an extensive negative workup at an outside hospital and was treated empirically with ciprofloxacin for 2 weeks. the fever resolved but returned months later and he was readmitted with pancytopenia, elevated alkaline phosphatase and ground glass opacities on t ...201323576657
a whole blood assay as a simple, broad assessment of cytokines and chemokines to evaluate human immune responses to mycobacterium tuberculosis antigens.in vitro stimulation of whole blood or isolated peripheral blood cells with specific antigens is used for several purposes. we sought to identify a reliable, reproducible, fast and feasible in vitro method to assess human cellular immune responses to mycobacterium tuberculosis. in contrast to peripheral blood mononuclear cell (pbmc) culture, a whole blood assay (wba) provides a more physiological environment, which may provide a broader assessment of serum biomarker, biosignature profiles. twent ...201323571106
modelling the impact of vaccination on tuberculosis in badgers.tuberculosis (tb) in livestock, caused by mycobacterium bovis, persists in many countries. in britain, efforts to control tb through the culling of badgers (meles meles), the principal wildlife host, have so far been unsuccessful, and there is significant interest in vaccination of badgers as an alternative or complementary strategy [corrected]. using a simulation model, we show that where tb is self-contained within the badger population and there are no external sources of infection, limited-d ...201323570613
biological evaluation of bisbenzaldehydes against four mycobacterium species.a series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant mycobacterium tuberculosis, against virulent mycobacterium bovis, against mycobacterium ulcerans and against two mycobacterium avium subspecies. among the 33 substances that were tested, compound 12, i.e. 4,4'-[1,12-dodecanediyl(oxy)]bisbenzaldehyde, emerged as the most promising hit. its activity was f ...201323567963
whole-transcriptome, high-throughput rna sequence analysis of the bovine macrophage response to mycobacterium bovis infection in vitro.mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. in the current study, we have analysed and compared the transcriptomes of m. bovis-infected monocyte-derived macrophages (mdm) purified from six holstein-friesian females with the transcriptomes of non-infected control mdm from the same animals over a 24 h period using stran ...201323565803
the potential for transmission of bcg from orally vaccinated white-tailed deer (odocoileus virginianus) to cattle (bos taurus) through a contaminated environment: experimental findings.white-tailed deer (odocoileus virginianus) experimentally infected with a virulent strain of mycobacterium bovis have been shown to transmit the bacterium to other deer and cattle (bos taurus) by sharing of pen waste and feed. the risk of transmission of m. bovis bacille calmette-guerin (bcg) vaccine from orally vaccinated white-tailed deer to other deer and cattle, however, is not well understood. in order to evaluate this risk, we orally vaccinated 14 white-tailed deer with 1×10(9) colony form ...201323565211
cd4+ cell-dependent granuloma formation in humanized mice infected with mycobacteria.we have used humanized mice, in which human immune cells differentiate de novo from transplanted cord blood progenitor cells, to study the human immune responses to infection with mycobacterium bovis bacillus calmette-guérin and mycobacterium tuberculosis. granulomas with a core containing giant cells, human cd68(+) macrophages, and high bacilli numbers surrounded by a layer of cd3(+) t cells and a fibrotic response encapsulating the lesions were observed in livers and lungs from bacillus calmet ...201323559373
disparate host immunity to mycobacterium avium subsp. paratuberculosis antigens in calves inoculated with m. avium subsp. paratuberculosis, m. avium subsp. avium, m. kansasii, and m. bovis.the cross-reactivity of mycobacterial antigens in immune-based diagnostic assays has been a major concern and a criticism of the current tests that are used for the detection of paratuberculosis. in the present study, mycobacterium avium subsp. paratuberculosis recombinant proteins were evaluated for antigenic specificity compared to a whole-cell sonicate preparation (mps). measures of cell-mediated immunity to m. avium subsp. paratuberculosis antigens were compared in calves inoculated with liv ...201323554467
cyclic amp-dependent protein lysine acylation in mycobacteria regulates fatty acid and propionate metabolism.acetylation of lysine residues is a posttranslational modification that is used by both eukaryotes and prokaryotes to regulate a variety of biological processes. here we identify multiple substrates for the camp-dependent protein lysine acetyltransferase from mycobacterium tuberculosis (katmt). we demonstrate that a catalytically important lysine residue in a number of fadd (fatty acyl coa synthetase) enzymes is acetylated by katmt in a camp-dependent manner and that acetylation inhibits the act ...201323553634
tubercular lesion of the foot presenting as epithelioma.tuberculosis continues to be the biggest public health problem worldwide. tuberculosis verrucosa cutis (tvc) is a verrucose form of cutaneous tuberculosis that occurs in previously sensitised individuals due to exogenous reinfection with mycobacterium tuberculosis or mycobacterium bovis, and it reflects good cell-mediated immunity. an elderly man presented with multiple fungating growths, which were painless but associated with mild itching and serous discharge, on the right foot for 40 years. t ...201323546037
heterozygosity at the a625c polymorphic site of the myd88 gene is associated with mycobacterium bovis infection in cattle.the study demonstrates that in cattle, animals heterozygous at the myd88 a625c polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis (odds ratio [or] = 0.19; p = 6 × 10(-12)). the reduced risk, however, does not extend to animals with latent pulmonary tuberculosis (or = 0.83; p = 0.40). heterozygosity at the a625c single nucleotide polymorphism is associated with intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase (nos). accor ...201323545302
factors associated with bovine tuberculosis confirmation rates in suspect lesions found in cattle at routine slaughter in great britain, 2003-2008.bovine tuberculosis (btb) is one of the most complex and intractable animal health problems facing the british cattle industry today. the inspection of carcasses from cattle sent to slaughter is part of routine surveillance for btb in great britain (gb). tissue with suspect lesions from cattle from herds previously considered uninfected with btb is sent to the animal health and veterinary laboratories agency (ahvla) for culture and histopathological examination for mycobacterium bovis infection. ...201323540447
long-term temporal trends and estimated transmission rates for mycobacterium bovis infection in an undisturbed high-density badger (meles meles) population.we describe epidemiological trends in mycobacterium bovis infection in an undisturbed wild badger (meles meles) population. data were derived from the capture, clinical sampling and serological testing of 1803 badgers over 9945 capture events spanning 24 years. incidence and prevalence increased over time, exhibiting no simple relationship with host density. potential explanations are presented for a marked increase in the frequency of positive serological test results. transmission rates (r0) e ...201323537573
surveillance and movements of virginia opossum (didelphis virginiana) in the bovine tuberculosis region of michigan.wildlife reservoir hosts of bovine tuberculosis (btb) include eurasian badgers (meles meles) and brushtail possum (trichosurus vulpecula) in the uk and new zealand, respectively. similar species warrant further investigation in the northern lower peninsula of michigan, usa due to the continued presence of btb on cattle farms. most research in michigan, usa has focused on interactions between white-tailed deer (odocoileus virginianus) and cattle (bos taurus) for the transmission of the infectious ...201323531427
comparison of immune peripheral blood cells in tuberculin reactor cattle that are seropositive or seronegative for mycobacterium bovis antigens.bovine tuberculosis (btb) is a major economic problem in animal husbandry and is a public health risk in nonindustrialized countries. it is generally accepted that protection against tb is generated through cell-mediated immunity. previous investigations have shown that wc1(+) γδ, cd4(+) and cd8(+) t-cell subpopulations are important in the immune response to btb. it is known that changes in the immune balance from a dominant t helper 1 (th1)-type response toward a more prominent th2 response ma ...201323523102
patterns of direct and indirect contact between cattle and badgers naturally infected with tuberculosis.tuberculosis (tb) due to infection with mycobacterium bovis is transmitted between cattle and badgers (meles meles) in the uk and ireland but it is unclear where or when transmission occurs. we investigated direct and indirect interactions between badgers and cattle using automated proximity loggers on animals and at badger latrines located on pasture, in an area of south-west england with a high-density badger population. direct contacts (interactions within 1.4 m) between badgers and cattle at ...201323522445
heterogeneity in the risk of mycobacterium bovis infection in european badger (meles meles) cubs.the behaviour of certain infected individuals within socially structured populations can have a disproportionately large effect on the spatio-temporal distribution of infection. endemic infection with mycobacterium bovis in european badgers (meles meles) in great britain and ireland is an important source of bovine tuberculosis in cattle. here we quantify the risk of infection in badger cubs in a high-density wild badger population, in relation to the infection status of resident adults. over a ...201323522097
evaluation of the interferon-γ assay on blood collected at exsanguination of cattle under field conditions for surveillance of bovine tuberculosis.development of point of concentration (poc) surveillance strategies for bovine tuberculosis (btb) would facilitate global efforts to eradicate btb. the interferon-gamma (ifnγ) assay can detect ifnγ responses to mycobacterium bovis in blood collected at commencement of exsanguination (coe) of experimentally challenged cattle but has not been evaluated under field conditions. the current study was aimed at determining (i) whether blood collected at coe of cattle at slaughter, under field condition ...201423522063
cd137 ligand signaling enhances myelopoiesis during infections.cd137 and its ligand are expressed in the bm, and conflicting data exist on the regulation of myelopoiesis by the cd137 receptor-ligand system. cd137(-/-) mice have increased numbers of myeloid cells in the bm, indicating an inhibitory influence of cd137 on myelopoiesis. however, cd137 also induces proliferation of hematopoietic progenitor cells and their myeloid differentiation, arguing for an enhancing effect. here we hypothesized that this latter case represents the situation during infection ...201323519951
mycobacterium bovis δmce2 double deletion mutant protects cattle against challenge with virulent m. bovis.a mycobacterium bovis strain deleted in mce2a and mce2b genes (m. bovis δmce2) was tested as an experimental vaccine in cattle challenged with a virulent m. bovis strain. three-and-a-half-month old calves (n = 5 to 6 per group) were vaccinated and challenged with a virulent strain of m. bovis by the intratracheal route 9 weeks after vaccination. a non-vaccinated group and a group vaccinated with bcg were included as controls. blood samples were collected to measure ifn-γ by an interferon-gamma r ...201323518075
what is your diagnosis? mycobacterium bovis in a cat. 201323517201
complete genome sequence of mycobacterium bovis bcg korea, the korean vaccine strain for substantial production.mycobacterium bovis bacillus calmette-guérin (bcg) is the only vaccine available against tuberculosis, and the strains used worldwide represent a family of daughter strains with distinct genotypic characteristics. here, we report the complete genome sequence of m. bovis bcg korea, the strain that will be actually used in korea for vaccine production.201323516200
dipterinyl calcium pentahydrate inhibits intracellular mycobacterial growth in human monocytes via the c-c chemokine mip-1β and nitric oxide.tuberculosis remains one of the top three leading causes of morbidity and mortality worldwide, complicated by the emergence of drug-resistant mycobacterium tuberculosis strains and high rates of hiv coinfection. it is important to develop new antimycobacterial drugs and immunomodulatory therapeutics and compounds that enhance antituberculous immunity. dipterinyl calcium pentahydrate (dcp), a calcium-complexed pterin compound, has previously been shown to inhibit human breast cancer cells and hep ...201323509148
modulation of angiogenic factor vegf by dna-hsp65 vaccination in a murine cns tuberculosis model.tuberculosis (tb) is a serious public health problem. development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. vascular endothelial growth factor (vegf) is a potent activator of vascular permeability and angiogenesis. vegf seems to participate in breakdown of the blood brain-barrier (bbb) in tuberculous meningitis (tbm), contributing to worsening of disease. therefore, the objective here was to extent the characterizatio ...201323491717
multiplex-pcr as an identity assay for mycobacterium bovis bcg moreau descendants.in the study, we assessed the identity of locally produced bcg vaccine via screening for the presence of genetic markers specific for particular mycobacterium bovis bcg substrains - rd8, rd2, senx3-regx3, rd14, rd16, δrd1, du2, a second copy of is6110, mutation d322g in phor, and deletions in fadd26-ppsa and rv3887c regions. in order to increase the specificity of the multiplex-pcr test for locally produced bcg vaccine, we have modified previously developed primer sets by the introduction of a p ...201323490534
tumour necrosis factor receptors and apoptosis of alveolar macrophages during early infection with attenuated and virulent mycobacterium bovis.apoptosis of macrophages has been reported as an effective host strategy to control the growth of intracellular pathogens, including pathogenic mycobacteria. tumour necrosis factor-α (tnf-α) plays an important role in the modulation of apoptosis of infected macrophages. it exerts its biological activities via two distinct cell surface receptors, tnfr1 and tnfr2, whose extracellular domain can be released by proteolysis forming soluble tnf receptors (stnfr1 and stnfr2). the signalling through tnf ...201323489296
enhanced protection against pulmonary mycobacterial challenge by chitosan-formulated polyepitope gene vaccine is associated with increased pulmonary secretory iga and gamma-interferon(+) t cell responses.induction of local (pulmonary) immunity plays a critical role in preventing dissemination of mycobacterium tuberculosis (m. tb) during the early infection stage. to induce specific mucosal immunity, chitosan, a natural cationic polysaccharide, was employed as a mucosal gene carrier and complexed with phsp65pep, our previously constructed multi-epitope gene vaccine, which induces splenic gamma-interferon (ifn-γ)(+) t helper cell 1 responses. the resultant chitosan-phsp65pep was administered intra ...201323489083
the capacity of mycobacterium tuberculosis complex species and m. bovis bcg substrains specific identification - implications for optimized pcr-based diagnostics in adverse events following vaccination suspected cases.the capacities of differentiation of mycobacterium bovis bcg from other members of m. tuberculosis complex species using pcr-rflp, multiplex pcr, and pcr-based genomic deletion analysis approaches were compared. in the study, mycobacteria isolated from patients suspected of adverse events following vaccination with bcg, primarily classified according presence of rd1 marker as virulent and avirulent mycobacteria, were used. the pcr-based genomic deletion analysis was found the best option for myc ...201223484413
transcriptional response of bovine monocyte-derived macrophages after the infection with different argentinean mycobacterium bovis isolates.infection of bovines with mycobacterium bovis causes important financial hardship in many countries presenting also a risk for humans. m. bovis is known to be adapted to survive and thrive within the intramacrophage environment. in spite of its relevance, at present the information about macrophage expression patterns is scarce, particularly regarding the bovine host. in this study, transcriptomic analysis was used to detect genes differentially expressed in macrophages derived from peripheral b ...201323484118
identification and characterization of rv0494: a fatty acid-responsive protein of the gntr/fadr family from mycobacterium tuberculosis.escherichia coli fadr, a member of the gntr family of transcription factors, plays dual roles in fatty acid metabolism. fadr-dna binding is inhibited by fatty acyl-coas, and thus fadr acts as a sensor of the fatty acid level in bacteria. we have identified fadr-binding sites in the upstream regions of genes showing altered expression after the disruption of fatty acid biosynthesis in mycobacterium tuberculosis. a fadr homologue in m. tuberculosis, rv0494, was identified, which binds to its opera ...201323475950
the consequences of vaccination with the johne's disease vaccine, gudair, on diagnosis of bovine tuberculosis.the single intradermal comparative cervical tuberculin skin-test (sicct) remains the primary surveillance tool to diagnose bovine tuberculosis (btb) in the uk. therefore, understanding the potential confounding influences on this test is important. this study investigated the effects of vaccination against johne's disease (jd) on the immunodiagnosis of btb using a mycobacterium bovis bcg vaccination model as a surrogate of m bovis infection. calves were vaccinated with either bcg (an attenuated ...201223475045
physicochemical and biological characterization of synthetic phosphatidylinositol dimannosides and analogues.native phosphatidylinositol mannosides (pims), isolated from the cell wall of mycobacterium bovis, and synthetic pim analogues have been reported to offer a variety of immunomodulating properties, including both suppressive and stimulatory activity. while numerous studies have examined the biological activity of these molecules, the aim of this research was to assess the physicochemical properties at a molecular level and correlate these characteristics with biological activity in a mouse model ...201323469864
improved detection of mycobacterium bovis infection in bovine lymph node tissue using immunomagnetic separation (ims)-based methods.immunomagnetic separation (ims) can selectively isolate and concentrate mycobacterium bovis cells from lymph node tissue to facilitate subsequent detection by pcr (ims-pcr) or culture (ims-mgit). this study describes application of these novel ims-based methods to test for m. bovis in a survey of 280 bovine lymph nodes (206 visibly lesioned (vl), 74 non-visibly lesioned (nvl)) collected at slaughter as part of the northern ireland bovine tb eradication programme. their performance was evaluated ...201323469275
neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses.microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. the nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. interleukin-27 (il-27) is a heterodimeric cytokine of the il-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. we show that il-27 gene expression is elevated in cord blood-de ...201323464355
immunogenicity and cross-reactivity against mycobacterium tuberculosis of proteoliposomes derived from mycobacterium bovis bcg.the only currently available vaccine against tuberculosis (tb) is mycobacterium bovis bacille calmette-guerin (bcg), which has inconsistent efficacy to protect against the disease in adults. m. tuberculosis (mtb) cell wall components have been implicated in the pathogenicity of tb and therefore have been a prime target for the identification and characterization of cell wall proteins with potential application in vaccine development. in this regard, proteoliposomes (pls) derived from mycobacteri ...201323458692
immunogenicity of recombinant mycobacterium bovis bacille calmette-guèrin clones expressing t and b cell epitopes of mycobacterium tuberculosis antigens.recombinant mycobacterium bovis bacille calmette-guèrin (rbcg) expressing three t cell epitopes of mycobacterium tuberculosis (mtb) ag85b antigen (p1, p2, p3) fused to the mtb8.4 protein (rbcg018) or a combination of these antigens fused to b cell epitopes from esat-6, cfp-10 and mtp40 proteins (rbcg032) were used to immunize balb/c mice. total igg responses were determined against mtb8.4 antigen and esat-6 and cfp-10 b cell epitopes after immunization with rbcg032. mice immunized with rbcg032 s ...201323458635
[prevention of tuberculosis: current approaches to development of vaccines].this review is focused on recent advances in development of new vaccines for the prevention of tuberculosis. the main reasons for lack of bcg vaccine efficacy in different populations and geographic regions are presented. design of new vaccines based on live modified strains of mycobacterium bovis bcg, attenuated strains of mycobacterium tuberculosis, recombinant proteins and viral vectors is considered in the specific examples. the usage of the heterologous "prime-boost" vaccination strategy ag ...201223457981
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