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increased protective efficacy of recombinant bcg strains expressing virulence-neutral proteins of the esx-1 secretion system.mycobacterium bovis bcg is presently the only available anti-tuberculosis vaccine used, worldwide. while bcg protects against miliary tuberculosis (tb) and tuberculoid meningitis in children, it often fails to protect against adult pulmonary tb. it is thus imperative that new improved anti-tb vaccines are developed. the integration of the esx-1 secretion system, absent from bcg due to the deletion of region of difference 1 (rd1), into the genome of bcg has been shown to confer to bcg::esx-1 enha ...201525869896
a case of infectious endocarditis due to bcg.the occurrence of bacillus calmette-guérin (bcg) disease following instillation for bladder cancer is commonly documented. the intravesical administration of bcg is generally safe, but may present severe complications. a fatal case of native aortic valve infectious endocarditis with septicemia due to bcg in a patient treated with intravesical instillation is reported herein.201525869076
the cyclic di-gmp phosphodiesterase gene rv1357c/bcg1419c affects bcg pellicle production and in vivo maintenance.bacteria living in a surface-attached community that contains a heterogeneous population, coated with an extracellular matrix, and showing drug tolerance (biofilms) are often linked to chronic infections. in mycobacteria, the pellicle mode of growth has been equated to an in vitro biofilm and meets several of the criteria mentioned above, while tuberculosis infection presents a chronic (latent) phase of infection. as mycobacteria lack most genes required to control biofilm production by other mi ...201525865678
molecular diagnosis of bovine tuberculosis in bovine and human samples: implications for zoonosis.to develop emerging diagnostic technique for bovine tuberculosis and to identify its potential risk factors.201525865192
evaluation of the efficiency of nested q-pcr in the detection of mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of mato grosso, brazil.bovine tuberculosis (btb) is a zoonotic disease caused by mycobacterium bovis, a member of the mycobacterium tuberculosis complex (mtc). the quick and specific detection of this species is of extreme importance, since btb may cause economic impacts, in addition to presenting imminent risks to human health. in the present study a nested real-time pcr test (nested q-pcr) was used in post-mortem evaluations to assess cattle carcasses with btb-suspected lesions. a total of 41,193 cattle slaughtered ...201525863190
some south african rubiaceae tree leaf extracts have antimycobacterial activity against pathogenic and non-pathogenic mycobacterium species.tuberculosis (tb) caused by mycobacterium tuberculosis remains an ongoing threat to human health. many plant species contain antimycobacterial compounds, which may serve as template molecules for new anti-tb drugs. the rubiaceae family is the largest family of trees in southern africa, and preliminary evidence revealed antimycobacterial activity in several species of the genus, motivating further studies. leaf extracts of 15 tree species from the rubiaceae family were screened for antimycobacter ...201525857273
an evaluation of the use of immunoglobulin a antibody response against mycobacterial antigens for the diagnosis of mycobacterium bovis infection in cattle.antibody responses are useful indicators of mycobacterium bovis infection in cattle. many studies have evaluated the ability of immunoglobulin g (igg) to serodiagnose bovine tuberculosis (tb). in the current study, immunoglobulin a (iga) and igg responses against the mpb70 and mpb83 antigens of m. bovis, the 38 kda phosphate-binding lipoprotein (psts1) that is a well-known serodiagnostic m. tuberculosis antigen, and a newly identified protein, termed rv1483c, were compared in m. bovis-infected a ...201525855362
[when will the new tuberculosis vaccine appear?].the problem of tuberculosis prophylaxis remains actual for many countries of the world including russia. the search of candidates for substitution of the only authorized bcg vaccine has been ongoing for some time, because it does not prevent reactivation of the causative agent in the latent stage and causes generalized bcg-infection in individuals with pronounced immune deficiency. in october 2013 in lille at the european congress "world vaccine 2013" results of multi-year projects and trials of ...201525842959
the buffalo co-infection conundrum.parasitic worms modulate host immunity, affecting co-infection with mycobacterium bovis (btb). ezenwa and jolles suggested that anthelmintic treatment reduced btb-induced mortality, but increased btb spread. reduced mortality should be weighed against the risk of increasing pathogen spread when adopting this strategy for human treatment of mycobacterium tuberculosis, btb, and hiv.201525818850
guillain-barré syndrome associated with mycobacterium bovis lymphadenitis.guillain-barré syndrome (gbs) is an autoimmune disease that can be triggered by different infectious agents. here we report the case of a 26-year-old algerian woman who developed gbs associated with a mycobacterium bovis cervical lymphadenitis. following intravenous immunoglobulin therapy, the patient's neurologic state returned to normal after 3 months. the lymphadenitis responded more slowly to the antituberculous treatment and an excision of necrotic cervical lymph nodes had to be performed f ...201525814190
role for nod2 in mycobacterium tuberculosis-induced inos expression and no production in human macrophages.m.tb, which causes tb, is a host-adapted intracellular pathogen of macrophages. macrophage intracellular prrs, such as nod proteins, regulate proinflammatory cytokine production in response to various pathogenic organisms. we demonstrated previously that nod2 plays an important role in controlling the inflammatory response and viability of m.tb and mycobacterium bovis bcg in human macrophages. various inflammatory mediators, such as cytokines, ros, and rns, such as no, can mediate this control. ...201525801769
expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with mycobacterium bovis proteins.increased levels of prolactin (prl) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (tb). to investigate the relationship between prl and prolactin receptor (prlr) expression with inflammatory response and apoptosis in monocytes, we used thp-1 cells stimulated with antigens of the mycobacterium bovis an5 strain culture filtrate protein (cfp-m. bovis). western blot (wb), real-time polymerase ch ...201525797370
recombinant mycobacterium bovis bcg for immunotherapy in nonmuscle invasive bladder cancer.in the past three decades, intravesical instillation of mycobacterium bovis bacille calmette-guérin (bcg) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. although bcg-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, bcg is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of ...201525794874
childhood bcg vaccination does not influence control of mycobacterium tuberculosis growth by human bronchoalveolar lavage cells.childhood vaccination with mycobacterium bovis bacille calmette-guérin (bcg) reduces the risk of infection with mycobacterium tuberculosis and the risk of severe forms of tuberculosis in children. the protection of adults from pulmonary tuberculosis is doubtful. this study evaluated the effect of the vaccination on the growth of m. tuberculosis human bronchoalveolar mononuclear cells (balmc).201525794470
methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.the emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. ribonucleotide reductase (rnr) is a key enzyme in dna replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of dna replication and repair. rnr has been extensively studied as an ideal target for dna inhibition, and several drugs that are already available on the market are used for ant ...201525782003
mycobacterium tuberculosis mce3e suppresses host innate immune responses by targeting erk1/2 signaling.crucial to the pathogenesis of the tuberculosis (tb)-causing pathogen mycobacterium tuberculosis is its ability to subvert host immune defenses to promote its intracellular survival. the mammalian cell entry protein 3e (mce3e), located in the region of difference 15 of the m. tuberculosis genome and absent in mycobacterium bovis bacillus calmette-guérin, has an essential role in facilitating the internalization of mammalian cells by mycobacteria. however, relatively little is known about the rol ...201525780035
protein energy malnutrition during vaccination has limited influence on vaccine efficacy but abolishes immunity if administered during mycobacterium tuberculosis infection.protein energy malnutrition (pem) increases susceptibility to infectious diseases, including tuberculosis (tb), but it is not clear how pem influences vaccine-promoted immunity to tb. we demonstrate that pem during low-level steady-state tb infection in a mouse model results in rapid relapse of mycobacterium tuberculosis, as well as increased pathology, in both mycobacterium bovis bcg-vaccinated and unvaccinated animals. pem did not change the overall numbers of cd4 t cells in bcg-vaccinated ani ...201525754202
cpg oligodeoxynucleotides as mucosal adjuvants.bacterial dna comprising palindromic sequences and containing unmethylated cpg is recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pdcs) and induces the production of interferon-α and chemokines, leading to the activation of a th1 immune response. therefore, synthetic equivalents of bacterial dna (cpg oligodeoxynucleotides) have been developed for clinical applications. they are usually phosphorothioated for in vivo use; this approach also leads to adverse effects as reported ...201525751765
diagnosis of bovine tuberculosis using a metal oxide-based electronic nose.electronic noses (e-noses) have been used for environmental monitoring, standardization of medicinal flavourings, food safety tests and diagnosis of infectious diseases based on the statistical analysis of volatile organic compounds (vocs). bovine tuberculosis (btb) is officially diagnosed using the intradermal skin test (ist), which is time-consuming and labour-intensive. therefore, a more convenient and rapid test with greater sensitivity would be advantageous as prescreening test. in this stu ...201525739902
pulmonary tuberculosis caused by mycobacterium bovis in china.the epidemiology of mycobacterium bovis infection in humans in china is unknown. in this study, pulmonary tuberculosis caused by m. bovis in china was studied. a total of 4069 clinical strains isolated from sputa during the 2007-2009 nationwide surveillance of drug-resistant tuberculosis in china were analyzed. m. bovis was identified by para-nitrobenzoic acid and thiophen-2-carboxylic acid hydrazide growth tests, spoligotyping and multiplex pcr amplification. in addition, a total of 1828 clinic ...201525736338
successful treatment of a mycotic multifocal thoracoabdominal aortic aneurysm as a late sequelae of intravesical bacillus calmette-guerin therapy: case report and literature review.bacillus calmette-guerin (bcg) is a live, attenuated strain of mycobacterium bovis commonly used for the treatment of superficial bladder carcinoma. intravesical bcg is well tolerated despite side effects that range from hematuria to sepsis syndrome. a very rare complication is vascular infection developing a mycotic bcg aneurysm, especially in the thoracoabdominal aorta (taaa). these are challenging to diagnose because of their scarcity, nontraditional culture media, slow growth, and are often ...201525736202
tale nickase-mediated sp110 knockin endows cattle with increased resistance to tuberculosis.transcription activator-like effector nuclease (talen)-mediated genome modification has been applied successfully to create transgenic animals in various species, such as mouse, pig, and even monkey. however, transgenic cattle with gene knockin have yet to be created using talens. here, we report site-specific knockin of the transcription activator-like effector (tale) nickase-mediated sp110 nuclear body protein gene (sp110) via homologous recombination to produce tuberculosis-resistant cattle. ...201525733846
tuberculosis origin: the neolithic scenario.this paper follows the dramatic changes in scientific research during the last 20 years regarding the relationship between the mycobacterium tuberculosis complex and its hosts - bovids and/or humans. once the m. tuberculosis and mycobacterium bovis genomes were sequenced, it became obvious that the old story of m. bovis evolving into the human pathogen should be reversed, as m. tuberculosis is more ancestral than m. bovis. nevertheless, the timescale and geographical origin remained an enigma. i ...201525726364
release of mycobacterial antigens.mycobacterium tuberculosis has evolved from a mycobacterium canettii-like progenitor pool into one of the most successful and widespread human pathogens. the pathogenicity of m. tuberculosis is linked to its ability to secrete/export/release selected mycobacterial proteins, and it is also established that active release of mycobacterial antigens is a prerequisite for strong immune recognition. recent research has enabled mycobacterial secretion systems and vesicle-based release of mycobacterial ...201525703550
spillover of mycobacterium bovis from wildlife to livestock, south 
africa.during august 2012-february 2013, bovine tuberculosis was detected in communal livestock bordering the greater kruger national park complex (gknpc) in south africa. using spacer oligonucleotide and variable number tandem repeat typing, we identified the mycobacterium bovis strain endemic in gknpc wildlife. our findings indicate bovine tuberculosis spillover from gknpc wildlife to neighboring livestock.201525695846
potential benefits of cattle vaccination as a supplementary control for bovine tuberculosis.vaccination for the control of bovine tuberculosis (btb) in cattle is not currently used within any international control program, and is illegal within the eu. candidate vaccines, based upon mycobacterium bovis bacillus calmette-guérin (bcg) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially btb-free. new diagnostic tests that differentiate infected from vaccinated animals (diva) offer the potential to introduce v ...201525695736
mycobacterium bovis infection in humans and cats in same household, texas, usa, 2012.mycobacterium bovis infection of cats is exceedingly rare in regions where bovine tuberculosis is not endemic. we describe the diagnosis and clinical management of pulmonary m. bovis infection in 2 indoor-housed cats and their association with at least 1 m. bovis-infected human in texas, usa, in september 2012.201525695666
mycobacterium bovis bcg-associated osteomyelitis/osteitis, taiwan. 201525695272
epidemiology of human mycobacterium bovis disease, california, usa, 2003-2011.we conducted a retrospective review of california tuberculosis (tb) registry and genotyping data to evaluate trends, analyze epidemiologic differences between adult and child case-patients with mycobacterium bovis disease, and identify risk factors for m. bovis disease. the percentage of tb cases attributable to m. bovis increased from 3.4% (80/2,384) in 2003 to 5.4% (98/1,808) in 2011 (p = 0.002). all (6/6) child case-patients with m. bovis disease during 2010-2011 had >1 parent/guardian who wa ...201525693687
liposome-encapsulated cpg enhances antitumor activity accompanying the changing of lymphocyte populations in tumor via intratumoral administration.although oligodeoxynucleotides containing cpg motifs (cpg-odn) are potent immune stimulators, the use of natural cpg-odn--phosphodiester-backbone cpg--has been limited due to its instability by nuclease in vivo. the aim of this study is to investigate the anticancer efficiency of cpg-odn capsulated using liposome, which enhances the stability of cpg-odn. we formulated lipoplex, encapsulated natural cpg-odn from mycobacterium bovis with liposome, and tested its immune stimulatory activity in vitr ...201525692533
microrna profiling of the bovine alveolar macrophage response to mycobacterium bovis infection suggests pathogen survival is enhanced by microrna regulation of endocytosis and lysosome trafficking.mycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (am) in the lung. here, we describe the first next-generation sequencing (rna-seq) approach to temporally profile mirna expression in primary bovine ams post-infection with m. bovis. one, six, and forty mirnas were identified as significantly differentially expressed at 2, 24 and 48 h post-infection, respectively. the diffe ...201525692199
epidemiology, diagnostics, and management of tuberculosis in domestic cattle and deer in new zealand in the face of a wildlife reservoir.the control of tuberculosis (tb) in cattle and farmed deer in new zealand has been greatly influenced by the existence of a wildlife reservoir of mycobacterium bovis infection, principally the australian brushtail possum (trichosurus vulpecula). the reduction in possum numbers in areas with endemic m. bovis infection through vigorous vector control operations has been a major contributor to the marked reduction in the number of infected cattle and farmed deer herds in the past two decades. manag ...201524992203
[pleural and peritoneal tuberculosis due to mycobacterium bovis]. 201525200214
improved detection of mycobacterium bovis in bovine tissues using immunomagnetic separation approaches.immunomagnetic separation (ims) represents a simple but effective method of selectively capturing and concentrating mycobacterium bovis, the causative agent of bovine tuberculosis (btb), from tissue samples. it is a physical cell separation technique that does not impact cell viability, unlike traditional chemical decontamination prior to culture. ims is performed with paramagnetic beads coated with m. bovis-specific antibody and peptide binders. once captured by ims, m. bovis cells can be detec ...201525399094
epidemiology and control of mycobacterium bovis infection in brushtail possums (trichosurus vulpecula), the primary wildlife host of bovine tuberculosis in new zealand.the introduced australian brushtail possum (trichosurus vulpecula) is a maintenance host for bovine tuberculosis (tb) in new zealand and plays a central role in the tb problem in this country. the tb-possum problem emerged in the late 1960s, and intensive lethal control of possums is now used to reduce densities to low levels over 8 million ha of the country. this review summarises what is currently known about the pathogenesis and epidemiology of tb in possums, and how the disease responds to p ...201525290902
antimycobacterial evaluation of novel [4,5-dihydro-1h-pyrazole-1-carbonyl]pyridine derivatives synthesized by microwave-mediated michael addition.the focus of this study is the synthesis and biological activity evaluation of a series of dibenzalaceton derivatives (3a-3n) and novel [4,5-dihydro-1h-pyrazole-1-carbonyl]pyridine derivatives (5a-5g) against mycobacterium bovis, bacillus calmette-guerin (bcg). dibenzalacetone derivatives were synthesized by benzaldehyde derivatives. the [4,5-dihydro-1h-pyrazole-1-carbonyl]pyridine derivatives were synthesized by michael addition reaction and using green chemistry microwave-mediated method. all ...201525219796
prolactin modulates cytokine production induced by culture filtrate proteins of m. bovis through different signaling mechanisms in thp1 cells.the immunomodulatory functions of prolactin (prl) are well recognized. augmented prl plasma levels were observed in patients with advanced tuberculosis (tb). recently, we have reported that lps and mycobacterium bovis (m. bovis) induced differential expression of prl receptor (prlr) isoforms in thp-1 cells and bovine macrophages, respectively. the aim of this work was to determine whether prl should be considered as a potential modulator of the signaling pathways and cytokine synthesis, induced ...201525218920
the adenylyl cyclase rv2212 modifies the proteome and infectivity of mycobacterium bovis bcg.all organisms have the capacity to sense and respond to environmental changes. these signals often involve the use of second messengers such as cyclic adenosine monophosphate (camp). this second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. genomic analysis in mycobacterium tuberculosis has identified 16 adenylyl cyclases (ac) and one phosphodiesterase, which produce and degrade camp, respective ...201525038956
nosocomial spread of mycobacterium bovis in domestic cats.five domestic cats were euthanased owing to confirmed or suspected mycobacterium bovis infection. the initial source of infection remains unclear. cat a was presented to a veterinary clinic in county kildare, ireland, with a discharging submandibular lesion. the infection appears to have been transmitted to four other cats through direct (cats b and c living in the same household as cat a) and non-direct (nosocomial spread during routine operations; cats d and e) contact over a 13.5-week period. ...201524710594
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
dermal vγ4(+) γδ t cells possess a migratory potency to the draining lymph nodes and modulate cd8(+) t-cell activity through tnf-α production.a large number of gamma delta t cells (γδ t cells) are located within epithelial tissues including the skin. in mice, epidermal and dermal γδ t cells consist of distinct subsets and have specific roles in cutaneous immune responses. a recent study demonstrated that γδ t cells and cutaneous dendritic cells migrate from the skin to the draining lymph nodes (lns). however, it remains unclear whether they regulate the antigen-specific immune response within the lns. herein, we investigated their pro ...201525493651
persistence of mycobacterium bovis bacillus calmette-guérin (bcg) danish in white-tailed deer (odocoileus virginianus) vaccinated with a lipid-formulated oral vaccine.mycobacterium bovis, the causative agent of tuberculosis in animals, has a broad host range, including humans. historically, public health concerns prompted programs to eradicate tuberculosis from cattle in many nations. eradication efforts decreased the prevalence of bovine tuberculosis; nevertheless, some countries encountered significant obstacles, not least of which was a wildlife reservoir of m. bovis. efforts to decrease the size of the affected wildlife populations have neither eliminated ...201423173832
differential tlr2 downstream signaling regulates lipid metabolism and cytokine production triggered by mycobacterium bovis bcg infection.the nuclear receptor pparγ acts as a key modulator of lipid metabolism, inflammation and pathogenesis in bcg-infected macrophages. however, the molecular mechanisms involved in pparγ expression and functions during infection are not completely understood. here, we investigate signaling pathways triggered by tlr2, the involvement of co-receptors and lipid rafts in the mechanism of pparγ expression, lipid body formation and cytokine synthesis in macrophages during bcg infection. bcg induces nf-κb ...201424120921
evaluation of protective efficacy conferred by a recombinant mycobacterium bovis bcg expressing a fusion protein of ag85a-esat-6.we previously constructed a recombinant bacille calmette-guérin (rbcg-ae) strain that could express a fused ag85a-esat-6 protein. that study suggested that the rbcg-ae strain was able to induce a higher titer of antibody and elicit a more long-lived and stronger th1-type cellular immune responses than the parental bcg strain, the rbcg-a strain (i.e., expressing ag85a), or the rbcg-e strain (i.e., expressing esat-6).201423357605
mycobacterium bovis bcg killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. regulatory t cells (tregs) and il-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. we have previously shown that mycobacterium bovis bcg killed by extended freeze-drying (efd bcg) decreases lung and colon inflammation by recruiting il-10-producing tregs. therefore, the aim of this study was to investigate the e ...201423962000
use of antigen-specific interleukin-2 to differentiate between cattle vaccinated with mycobacterium bovis bcg and cattle infected with m. bovis.we describe here the application of a novel bovine interleukin-2 (il-2) enzyme-linked immunosorbent assay (elisa) for the measurement of antigen-specific il-2 in cattle naturally infected with mycobacterium bovis and in cattle vaccinated with mycobacterium bovis bcg and then experimentally challenged with pathogenic m. bovis. supernatants from whole-blood cultures stimulated with mycobacterial antigen (bovine purified protein derivative [ppdb] or the peptide cocktail esat6-cfp10) were assessed u ...201424173026
utility of a fecal real-time pcr protocol for detection of mycobacterium bovis infection in african buffalo (syncerus caffer).a real-time pcr protocol for detecting mycobacterium bovis in feces was evaluated in bovine tuberculosis-infected african buffalo (syncerus caffer). fecal samples spiked with 1.42 × 10(3) cells of m. bovis culture/g and bacille calmette-guérin standards with 1.58 × 10(1) genome copies/well were positive by real-time pcr but all field samples were negative.201424171565
comparison of the immunogenicity and protection against bovine tuberculosis following immunization by bcg-priming and boosting with adenovirus or protein based vaccines.there is a requirement for vaccines or vaccination strategies that confer better protection against tb than the current live attenuated mycobacterium bovis bacillus calmette-guerin (bcg) vaccine for use in cattle. boosting with recombinant viral vectors expressing mycobacterial proteins, such as ag85a, has shown a degree of promise as a strategy for improving on the protection afforded by bcg. experiments in small animal models have indicated that broadening the immune response to include mycoba ...201424269321
genotypic characterization by spoligotyping and vntr typing of mycobacterium bovis and mycobacterium caprae isolates from cattle of tunisia.this work is an approach to the molecular epidemiology of mycobacterium tuberculosis complex (mtbc) bovine infections in tunisia. a total of 35 mtbc isolates from both lateral retropharyngeal lymph node samples of cattle slaughtered in different tunisian regions were genotyped by spoligotyping and variable number tandem repeat typing (vntr)-typing. spoligotyping allowed to identify two profiles not previously registered, namely sb2024, a mycobacterium caprae isolate from nabeul region (north eas ...201424158359
efficient activation of human t cells of both cd4 and cd8 subsets by urease-deficient recombinant mycobacterium bovis bcg that produced a heat shock protein 70-m. tuberculosis-derived major membrane protein ii fusion protein.for the purpose of obtaining mycobacterium bovis bacillus calmette-guérin (bcg) capable of activating human naive t cells, urease-deficient bcg expressing a fusion protein composed of mycobacterium tuberculosis-derived major membrane protein ii (mmp-ii) and heat shock protein 70 (hsp70) of bcg (bcg-dhtm) was produced. bcg-dhtm secreted the hsp70-mmp-ii fusion protein and effectively activated human monocyte-derived dendritic cells (dcs) by inducing phenotypic changes and enhanced cytokine produc ...201424152387
isolation and molecular characterization of mycobacterium bovis from kafue lechwe (kobus leche kafuensis) from zambia.bovine tuberculosis (btb) is a chronic bacterial disease caused by mycobacterium bovis. infections due to m. bovis, which serves as a stable reservoir, can pose serious challenge to control and eradicate in both wildlife and livestock at the interface. this study aimed at isolating and characterizing m. bovis from kafue lechwe (kobus leche kafuensis) and black lechwe (kobus leche smithemani) at the animal/human interface in zambia. the samples with lesions compatible with btb collected during th ...201424146292
synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes.a series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. the derivatives were prepared by a sequential synthetic strategy including substitution at n-1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. the derivatives were t ...201424103309
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
mycobacterium bovis: a rare cause of hand tenosynovitis. 201423340760
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
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
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
identification of the target protein of agelasine d, a marine sponge diterpene alkaloid, as an anti-dormant mycobacterial substance.one of the major reasons for the wide epidemicity of tuberculosis and for the necessity for extensive chemotherapeutic regimens is that the causative agent, mycobacterium tuberculosis, has an ability to become dormant. therefore, new lead compounds that are anti-bacterial against m. tuberculosis in both active and dormant states are urgently needed. marine sponge diterpene alkaloids, agelasines b, c, and d, from an indonesian marine sponge of the genus agelas were rediscovered as anti-dormant-my ...201424243718
evaluation of single and comparative intradermal tuberculin tests for tuberculosis eradication in caprine flocks in castilla y león (spain).goats can act as reservoirs for tuberculosis (tb) infection. the main etiological agents of tb in goats are mycobacterium caprae and mycobacterium bovis and they infect also a wide range of domestic and wild animals and humans. control programmes based mainly on the application of single and comparative intradermal tuberculin (sit and scit respectively) tests are being implemented in certain regions of spain with a high density of caprine flocks as castilla y león, including goats with epidemiol ...201424239314
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
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
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
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
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
assessment of t cell response to novel mycobacterium tuberculosis synthetic overlapping peptides mixtures (rv2659 and rv2660) and esat-6 in egyptian patients.tuberculosis (tb) remains one of the major challenges to the global public health. the most powerful tools in any tb control program are prompt diagnosis and successful treatment of patients with active contagious disease. for almost 100 years the tuberculin skin test (tst) has been used to support the diagnosis of active and latent tb infection. the tst has a number of limitations, most notable low specificity in bcg vaccinated individuals due to cross-reactive components in ppd and the mycobac ...201425812354
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
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