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cellular immune responses in mice induced by m. tuberculosis pe35-dna vaccine construct.the pe35 (rv3872) gene of mycobacterium tuberculosis is present in the region of difference (rd) 1 that is deleted in all vaccine strains of mycobacterium bovis bcg. the aim of this study was to clone pe35 dna into a dna vaccine plasmid with cmv promoter and interleukin-2 secretory signal and evaluate the recombinant plasmid for induction of antigen-specific cellular responses in mice. dna corresponding to pe35 was pcr-amplified from the genomic dna of m. tuberculosis h(37) rv, cloned into pgemt ...201121812801
preliminary data of different methods for the indirect diagnosis of mycobacterium bovis infection.we compared the response induced by quantiferon-tb gold antigens to that obtained with the intradermal comparative tuberculin test and bovigam assay. our results showed that the quantiferon-tb gold technique used in humans could also be applied for the diagnosis of tb infection in cattle.201121811754
low oral bcg doses fail to protect cattle against an experimental challenge with mycobacterium bovis.studies were undertaken to determine whether a dose of oral mycobacterium bovis bacillus calmette-guérin (bcg) which did not induce skin test reactivity could protect cattle against bovine tuberculosis (tb). groups of calves (n = 9) were vaccinated by administering 10(8), 10(7) or 10(6) colony forming units (cfu) of bcg orally or 10(6) cfu subcutaneous (s.c.) bcg. a control group (n = 10) was not vaccinated. all animals were challenged with m. bovis 18 weeks after vaccination and euthanized and ...201121807560
diva reagents for bovine tuberculosis vaccines in cattle.significant progress has been made in the development of specific antigens that allow the differentiation of bcg-vaccinated and mycobacterium bovis-infected cattle (the differential diagnosis of infected from vaccinated individuals test). this has been greatly facilitated by the completion of the genome sequences of mycobacterium tuberculosis, m. bovis and bcg pasteur and the application of comparative genome and transcriptome analysis to define differentiating infected from vaccinated animals ( ...201121806401
radiographic findings in cats with mycobacterial infections.this study describes radiographic changes associated with mycobacterial infection in 33 domestic cats confirmed by culture or interferon-gamma testing. infection was seen most frequently in adult (average age 5.7years; range 1.5-12years), non-pedigree (87%; 27/31), neutered male cats (69%; 22/32). the most common infections were mycobacterium microti (60%; 18/30) and mycobacterium bovis (37%; 11/30); mycobacterium avium and mycobacterium malmoense were infrequently cultured (3% of each; 1/30). r ...201121803626
loss of anti-mycobacterial efficacy in mice over time following vaccination with mycobacterium bovis bacillus calmette-guérin.mycobacterium bovis bacillus calmette-guérin (bcg) is the most often used vaccine worldwide and sole vaccine against tuberculosis. bcg is protective against severe form of childhood tuberculosis but less or not protective to adult pulmonary tuberculosis. therefore, improved vaccination strategies and development of new tuberculosis vaccines are urgent demands. for those purposes, appropriate animal models that reflect human are critically useful. however, in animal models, bcg vaccination protec ...201121803102
expression of ompatb is dependent on small membrane proteins in mycobacterium bovis bcg.small membrane proteins emerge as a novel class of regulatory molecules in bacteria. experiments carried out in mycobacterium bovis bcg indicate that the ompatb gene (rv0899), encoding a major outer membrane protein, is organized in operon with rv0900 and rv0901, encoding two small proteins with a predicted transmembrane domain. fractioning experiment confirmed the association of rv0901 with the membrane fraction. to investigate the role of rv0900 and rv0901 in m. bovis bcg, we have constructed ...201121802366
inhibition of allergen-induced airway remodeling by neonatal bacillus calmette-guerin vaccination is associated with interferon-gamma-producing t cells but not regulatory t cells in mice.epidemiological assessments of patients and studies using animal models show that exposure to mycobacterium bovis bacillus calmette-guerin (bcg) vaccine in early life prevents asthma development. however, little is known about the potential of neonatal bcg vaccination in preventing the development of airway remodeling of asthma.201121802025
polyantigenic interferon-? responses are associated with protection from tb among hiv-infected adults with childhood bcg immunization.surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (tb) have not been identified.201121799772
bcg mediated protection against w-beijing strains of mycobacterium tuberculosis is diminished concomitant with the emergence of regulatory t cells.despite issues relating to variable efficacy in the past, the bcg vaccine remains the basis for new generation recombinant vaccines currently in clinical trials. to date, vaccines have mostly been tested against laboratory strains, and not against the newly emerging clinical strains. in this study we evaluated the ability of bcg pasteur to protect mice from aerosol infections with two highly virulent w-beijing clinical strains, hn878 and sa161. in a conventional thirty day protection assay bcg w ...201121795460
cathelicidin is involved in the intra-cellular killing of mycobacteria in macrophages.macrophages have been shown to kill mycobacterium tuberculosis through the action of the antimicrobial peptide cathelicidin (camp), whose expression was shown to be induced by 1,25-dihydroxyvitamin d3 (1,25d3). here, we investigated in detail the anti-mycobacterial effect of murine and human cathelicidin against m. smegmatis and m. bovis-bcg infections. we have synthesized novel ll-37 peptide variants that exhibited potent in vitro bactericidal activity against m. smegmatis, m. bovis bcg and m. ...201121790937
ipr1 gene mediates raw 264.7 macrophage cell line resistance to mycobacterium bovis.tuberculosis due to mycobacterium bovis (m. bovis) seriously affects efficiency of animal production with impacts on public health as well. effective programs of prevention and eradication of m. bovis infection therefore are urgently needed. intracellular pathogen resistance gene 1 (ipr1), is well known to mediate innate immunity to m. tuberculosis (mtb), but there are no reports as to whether ipr1 can enhance the phagocytic ability of macrophage against m. bovis. in the present investigation, r ...201121790702
the microrna mir-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-?interferon-? (ifn-?) has a critical role in immune responses to intracellular bacterial infection. micrornas (mirnas) are important in the regulation of innate and adaptive immunity. however, whether mirnas can directly target ifn-? and regulate ifn-? production post-transcriptionally remains unknown. here we show that infection of mice with listeria monocytogenes or mycobacterium bovis bacillus calmette-guérin (bcg) downregulated mir-29 expression in ifn-?-producing natural killer cells, cd4(+) ...201121785411
mycobacterial infection after intravesical bacillus calmette-guërin treatment for bladder cancer: a case report.bacillus calmette-guërin (bcg) has been traditionally used as a vaccine against tuberculosis. further, intravesical administration of bcg has been shown to be effective in treating bladder cancer. although bcg contains a live attenuated strain of mycobacterium bovis, complications such as m. bovis bcg infection caused by bcg administration are extremely rare. here, we report a case of bcg infection occurring after intravesical bcg therapy. a 67-yr-old man presented with azotemia and weight loss. ...201121779195
lesion distribution and epidemiology of mycobacterium bovis in elk and white-tailed deer in south-western manitoba, canada.surveillance for mycobacterium bovis in free-ranging elk (cervus elaphus) and white-tailed deer (odocoileus virginianus) from south-western manitoba was carried out from 1997 to 2010 to describe the lesions, epidemiology, and geographic distribution of disease. tissues were cultured from animals killed by hunters, culled for management, blood-tested, or found opportunistically. period prevalence in elk was approximately six times higher than deer, suggesting a significant reservoir role for elk, ...201121776351
the effect of mycobacterium avium complex infections on routine mycobacterium bovis diagnostic tests.bovine tuberculosis (btb) is diagnosed in naturally infected populations exposed to a wide variety of other pathogens. this study describes the cell-mediated immune responses of cattle exposed to mycobacterium avium subspecies paratuberculosis (map) and mycobacterium avium subspecies avium with particular reference to routine antefmortem mycobacterium bovis diagnostic tests. the ifn-? released in response to stimulated blood was found to peak later in the map-exposed group and was more sustained ...201121772961
neonatal lung immune responses show a shift of cytokines and transcription factors towards th2 and a deficit in conventional and plasmacytoid dendritic cells.the high incidence of lung-damaging life-threatening respiratory infections in infants may be related to the immaturity of their immune systems. to determine whether lung immune features differ in early life compared with those in adulthood, whole lung as well as lung t lymphocyte and dendritic cell responses were investigated in balb/c neonates versus adults. higher expression of gata-3 and rapid and sustained production of type 2 cytokines by lung explants after in vitro exposure to anti-cd3 w ...201121770043
recurrence of bovine tuberculosis breakdowns in great britain: risk factors and prediction.bovine tuberculosis (btb) is an important economic disease worldwide with implications for both animal and human health. in great britain the number of herds that test positive for btb, termed "breakdowns", has increased over the last two decades. despite more intensive testing during a breakdown, around 23% of breakdowns recur within 12 months of the previous breakdown ending, and around 38% within 24 months. these "recurrent" breakdowns may be important for onward transmission of infection. de ...201121767886
a method to extract intact and pure rna from mycobacteria.we describe a high-yielding, simple, and aerosol-free protocol for the isolation of rna from mycobacteria that does not require sophisticated instruments. the method yielded 50µg of rna from 10(7) cells, 50 times more than a recently reported method. our method can extract total rna from aerobically grown bacteria and from in vitro hypoxia-induced dormant bacilli and mycobacteria residing within infected macrophages.201121767523
improved laboratory diagnosis of tuberculosis - the indian experience.tuberculosis (tb) is the leading cause of death worldwide attributable to a single infectious disease agent. india has more new tb cases annually than any other country. in 2008, india accounted for a fifth of the estimated 9.4 million tb cases globally. there is an overwhelming need for improving tb diagnostics in india through the use of cost effective, patient-friendly methods appropriate to different tiers of the country health system. substantial progress has been made in india in the field ...201121764383
ß-glucans inhibit intracellular growth of mycobacterium bovis bcg but not virulent mycobacterium tuberculosis in human macrophages.the yeast polysaccharide, ß-glucan, has been shown to promote both anti-microbial and anti-tumor activities through its interaction with macrophages. here we analyzed the effects of an insoluble whole glucan particle (wgp), a 1,3/1,6-ß-glucan from saccharomyces cerevisiae, and a soluble poly-1-6-ß-d-glucopyranosyl-1-3-ß-d-glucopyranose (pgg), a hydrolytic product of wgp, on the anti-microbial response of human macrophages against mycobacterial infection. treatment of macrophages with wgp and pgg ...201121762773
role of p27 -p55 operon from mycobacterium tuberculosis in the resistance to toxic compounds.abstract:201121762531
limitations of spoligotyping and variable number tandem repeat typing for molecular tracing of mycobacterium bovis in a high diversity setting.this study describes the attempt to trace the first mycobacterium bovis outbreak in alpacas (lama pacos) in spain by spoligotyping and vntr analysis. due to high genotype diversity no matching source was identified, but local expansion of a clonal group was found and its significance for molecular tracing is discussed.201121752973
localized reactive badger culling increases risk of bovine tuberculosis in nearby cattle herds.human and livestock diseases can be difficult to control where infection persists in wildlife populations. control of bovine tuberculosis (btb) in british cattle is complicated by the maintenance of mycobacterium bovis (the causative agent of btb) in badgers, acting as reservoirs of infection. although over 20 000 badgers were culled to control btb between 1975 and 1997, the incidence of btb in cattle has substantially increased in parts of great britain in recent decades. our case-control study ...201121752812
deda protein relates to action-mechanism of halicyclamine a, a marine spongean macrocyclic alkaloid, as an anti-dormant mycobacterial substance.a macrocyclic alkaloid, halicyclamine a, was re-discovered from an indonesian marine sponge of haliclona sp. 05a08 as an anti-dormant mycobacterial substance. to clarify action-mechanism of halicyclamine a, halicyclamine a-resistant strains were screened from the transformants of mycobacterium smegmatis with the genomic dna library of m. bovis bcg, which were constructed in the multi-copy shuttle cosmid pyub145. sequencing analysis of the cosmids isolated from the halicyclamine a-resistant trans ...201121747743
patterns of in vitro cell-death, metaloproteinase-9 and pro-inflammatory cytokines in human monocytes induced by the bcg vaccine, moreau strain.mononuclear cells have been implicated in the primary inflammatory response against mycobacteria. yet, little is known about the interaction of mycobacterium bovis bacillus calmette-guerin (bcg) with human monocytes. here, we investigated the potential of bcg moreau strain to induce in vitro specific cell-death utilizing a flow cytometry approach that revealed an increase in apoptosis events in bcg-stimulated monocytes from healthy adults. we also detected a concomitant release of interleukin 1 ...201121745518
evaluation of pathogenesis caused in cattle and guinea pig by a mycobacterium bovis strain isolated from wild boar.abstract: background: in many regions of the world, wild mammals act as reservoir of mycobacterium bovis, a situation that prevents the eradication of bovine tuberculosis. in order to observe whether a strain isolated from a wild boar, previously tested as highly virulent in a mice model, is also virulent in cattle, we performed cattle experimental inoculation with this strain results: groups of friesian calves were either infected with the wild boar strain m. bovis 04-303 or with the bovine str ...201121745408
primary mycobacterium bovis infection revealed by erythema nodosum.mycobacterium bovis is responsible for a zoonosis originating in cattle. this disease has rarely affected man in industrialised countries since the establishment of veterinary surveillance in cattle. we report the case of a young female patient who developed a mycobacterium bovis primary infection revealed by erythema nodosum. infection was probably due to the consumption of non-pasteurised milk in morocco. this clinical manifestation is rare and physicians ought to be aware of this imported pat ...201121740681
Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3.The active vitamin D metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)(2)D(3) from 25-hydroxyvitamin D(3) (25(OH)D(3)) by the enzyme 1+¦-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1+¦-hydroxylase in stimulated ...201121738762
the therapeutic effects of r8-liposome-bcg-cws on bbn-induced rat urinary bladder carcinoma.the present gold standard for bladder cancer is mycobacterium bovis bacillus calmette-gu+®rin (bcg) immunotherapy, but serious side-effects are common. we previously reported that c3h/hen mice vaccinated with a mixture of mbt-2 cells and artificial bcg, octaarginine-modified liposomes incorporating the cell wall of bcg (r8-liposome-bcg-cw), significantly inhibited growth of r8-liposome-bcg-cw pretreated mbt-2 cells. our aim was to determine if a non-live bacterial agent could be as efficacious a ...201121737624
pathology of post primary tuberculosis of the lung: an illustrated critical review.post primary tuberculosis occurs in immunocompetent adults, is restricted to the lungs and accounts for 80% of all clinical cases and nearly 100% of transmission of infection. the supply of human tissues with post primary tuberculosis plummeted with the introduction of antibiotics decades before the flowering of research using molecular methods in animal models. unfortunately, the paucity of human tissues prevented validation of the models. as a result, it is a paradigm of contemporary research ...201121733755
characterization of the risk of deer-cattle interactions in minnesota by use of an on-farm environmental assessment tool.to characterize the risk of interactions that may lead to the transmission of mycobacterium bovis between cattle and white-tailed deer (odocoileus virginianus) on farms in northern minnesota.201121728853
the regulatory effects of polyporus polysaccharide on the nuclear factor kappa b signal pathway of bladder cancer cells stimulated by bacillus calmette-guerin.to detect the effects of polyporus polysaccharide (pps), bacillus calmette-guerin (bcg), and their combination on the nuclear factor kappa b (nf-κb) signaling pathway associated-gene expression and investigate the molecular mechanisms of the toxic-reducing effect of pps in coordination with bcg against bladder cancer.201121725879
[m.-ábovis and m.-ácaprae infections in aquitaine: a clinico-epidemiologic study of 15-ápatients.]the agent of bovine tuberculosis, mycobacterium bovis, is a zoonosis which can be transmitted to human beings. in france, the prevalence of tuberculosis due to m.-ábovis has drastically decreased, both for animals and humans, since public health measures were introduced to prevent its transmission. however, a new outbreak of the disease is noted among cattle in several french areas and more particularly in aquitaine. in 2008, 40% of bovine tuberculosis french cases provided from aquitaine. from ...201121723048
systemic bcg immunization induces persistent lung mucosal multifunctional cd4 t(em) cells which expand following virulent mycobacterial challenge.to more closely understand the mechanisms of how bcg vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. given the established central role of cd4 t cells in bcg induced immunity, we sought to characterise the generation of memory cd4 t cell responses to bcg vaccination and m. bovis infection in a murine challenge model. we demonstrate that a single systemic bcg vaccination induces distinct systemic and mucosal populations of t ...201121720558
[Mendelian susceptibility to mycobacterial infections and defect in macrophages respiratory burst]. 201121718638
expression of tmrna in mycobacteria is increased by antimicrobial agents that target the ribosome.the specialized rna, tmrna, is a central component of prokaryote trans-translation; a process that salvages stalled translational complexes. evidence from other bacteria suggested that exposure to ribosome inhibitors elevated tmrna levels, although it was unclear whether such changes resulted from increased tmrna synthesis. consequently, this study was initiated to determine the effect of ribosome inhibitors on the expression of tmrna in mycobacteria. exposure of mycobacterium smegmatis to ribos ...201121718348
immune responses to the enduring hypoxic response antigen rv0188 are preferentially detected in mycobacterium bovis infected cattle with low pathology.the dosr regulon and the enduring hypoxic response (ehr) define a group of m. tuberculosis genes that are specifically induced in bacilli exposed in vitro to conditions thought to mimic the environment encountered by mycobacteria during latent infection. although well described in humans, latent mycobacterial infection in cattle remains poorly understood. thus, the aim of this study was to identify antigens that may potentially disclose cattle with latent m. bovis infection. to this end, we init ...201121712953
coresistance to isoniazid and ethionamide maps to mycothiol biosynthetic genes in mycobacterium bovis.a search to identify new mechanisms of isoniazid resistance in mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (msha) or the cysteine ligase (mshc). these mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. this study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial ...201121709101
controlling tuberculosis in a llama (lama glama) herd using clinical signs, tuberculin skin testing and serology.an outbreak of tuberculosis (tb), caused by mycobacterium bovis, was investigated in a small herd of llamas (lama glama). based on three ante-mortem diagnostic methods (clinical signs, tuberculin skin test reactions, and 'rapid test' serology), 12 llamas were selected for examination post-mortem. grossly visible lesions suspicious of tb were observed in eight animals, four of which had exhibited clinical signs, one was a skin test 'reactor', and three had been seropositive. m. bovis was isolated ...201121704542
immunogenicity and protective efficacy of a tuberculosis dna vaccine expressing a fusion protein of ag85b-esat6-hspx in mice.tuberculosis remains a major infectious disease worldwide due to the low efficacy of available vaccine of the mycobacterium bovis bacillus calmette-gu+®rin (bcg). dna vaccines are especially promising candidates; however, the efficacy of dna vaccine expressing single antigen of mycobacterium tuberculosis (mtb) is limited. in this study, a plasmid dna vaccine, paeh, was constructed and designed to express a fusion protein of the ag85b, esat6, and hspx of mtb. its immunogenicity and protective eff ...201121704108
tuberculosis due to mycobacterium bovis and mycobacterium caprae in sheep.tuberculosis was diagnosed in three flocks of sheep in galicia, spain, in 2009 and 2010. two flocks were infected with mycobacterium bovis and one flock was infected with mycobacterium caprae. infection was confirmed by the comparative intradermal tuberculin test, bacteriology, molecular analysis and histopathology. sheep have the potential to act as a reservoir for tuberculosis.201121703887
isoniazid resistance among bacillus calmette guerin strains: implications on bladder cancer immunotherapy related infections.bacillus calmette guerin (bcg) immunotherapy is widely used for treatment of superficial bladder transitional cell carcinoma. infectious complications while rare can be serious and severe disseminated infections as well as sepsis has been reported. there are no standard guidelines to direct therapy of these complications. isoniazid is a commonly and widely used component of the various treatment regimens. various strains of bcg are used for treatment of bladder cancer as well as vaccinations. th ...201121703038
a histone-like protein of mycobacteria possesses ferritin superfamily protein-like activity and protects against dna damage by fenton reaction.iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the fenton reaction. in addition, ferric ion shows low solubility under physiological conditions. to overcome these obstacles living organisms possess ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. these proteins minimize ...201121698192
identification of n6,n6-dimethyladenosine in transfer rna from mycobacterium bovis bacille calmette-gu+®rin.there are more than 100 different ribonucleoside structures incorporated as post-transcriptional modifications, mainly in trna and rrna of both prokaryotes and eukaryotes, and emerging evidence suggests that these modifications function as a system in the translational control of cellular responses. however, our understanding of this system is hampered by the paucity of information about the complete set of rna modifications present in individual organisms. to this end, we have employed a chroma ...201121694680
study of peripheral blood cell populations involved in the immune response of goats naturally infected with mycobacterium caprae.tuberculosis in goats caused by mycobacterium bovis and mycobacterium caprae has noteworthy sanitary and economic implications. current diagnostic assays are based on cellular immunity and although they have demonstrated a high sensitivity, some animals remain undetected. in the present study, flow cytometry has been used to determine changes in cd4+, cd8+ and cd25+ t cell populations in peripheral blood from naturally infected goats. proportion of lymphocytes producing ppd-specific interferon-g ...201121689835
[From genetics to genomics in the rational design of new Mycobacterium tuberculosis vaccines.]Tuberculosis (TB) is an infectious disease affecting people from all ages all over the world. It is estimated that one third of the world population lives infected with the causal agent: Mycobacterium tuberculosis. Despite availability and systematic administration of BCG vaccine in endemic areas, TB transmission remains elusive to control, partly because BGC efficacy has been shown to have wide variability (0-80%). Such variability in protection is attributed to factors including: the BCG strai ...201121684635
Mobility of late endosomal and lysosomal markers on phagosomes analyzed by fluorescence recovery after photobleaching.During phagosome maturation, the late endosomal marker Rab7 and the lysosomal marker LAMP1 localize to the phagosomes. We investigated the mobility of Rab7 and LAMP1 on the phagosomes in macrophages by fluorescence recovery after photobleaching (FRAP) analysis. Rab7 was mobile between the phagosomal membrane and the cytosol in macrophages that ingested latex beads during phagosome maturation. The addition of interferon-+¦ (IFN-+¦) restricted this mobility, suggesting that Rab7 is forced to bind ...201121683685
integrating contact network structure into tuberculosis epidemiology in meerkats in south africa: implications for control.empirical studies that integrate information on host contact patterns with infectious disease transmission over time are rare. the aims of this study were to determine the relative importance of intra-group social interactions in the transmission of tuberculosis (tb; mycobacterium bovis infection) in a population of wild meerkats (suricata suricatta) in south africa, and to use this information to propose an evidence-based intervention strategy to manage this disease. detailed behavioural observ ...201121683459
mycobacterium bovis bacillus calmette-gu+®rin killed by extended freeze-drying reduces colitis in mice.mycobacterium bovis bacillus calmette-gu+®rin (bcg), killed by extended freeze-drying (efd), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. we investigated the effects of efd bcg in mouse models of inflammatory bowel disease.201121683076
mycotic aneurysm of the aorta as a complication of bacillus calmette-gu+®rin instillation.bacillus calmette-gu+®rin (bcg) is a live attenuated strain of mycobacterium bovis that has been widely used for the treatment of superficial transitional cell carcinoma of the bladder. we describe a rare case of supra-renal mycotic aortic aneurysm secondary to bcg instillation in a 75-year-old male. patients presenting with systemic symptoms post-instillation, possibly with an aneurysm, should raise suspicion of bcg dissemination, which requires early instigation of anti-mycobacterial drugs.201121677913
a novel recombinant mycobacterium bovis bacillus calmette-guerin strain expressing human granulocyte macrophage colony-stimulating factor and mycobacterium tuberculosis early secretory antigenic target 6 complex augments th1 immunity.since mycobacterium bovis bacillus calmette-guerin strain (bcg) fails to protect adults from pulmonary tuberculosis (tb), there is an urgent need for developing a new vaccine. in this study, we constructed a novel recombinant bcg strain (rbcg) expressing human granulocyte macrophage colony-stimulating factor (gm-csf) and the 6 kda early secretory antigenic target (esat6) of mycobacterium tuberculosis, named rbcg:ge (expressing gmcsf-esat6 complex), and evaluated the immunogenicity of the constru ...201121676888
mycobacterium tuberculosis complex mycobacteria as amoeba-resistant organisms.most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the mycobacterium tuberculosis complex. an environmental source has been proposed for the animal mycobacterium bovis and the human mycobacterium canettii.201121673985
palaeogenomics of mycobacterium tuberculosis: epidemic bursts with a degrading genome.genome-scale analysis suggests that the last common ancestor of the mycobacterium tuberculosis complex and mycobacterium leprae diverged 36 million years ago, and members of the mycobacterium tuberculosis complex differentiated 40ôçê000 years ago. analysis of palaeomicrobiological data from a 17ôçê000-year-old sample from a bison and a 9000-year-old sample from a human being suggested that m tuberculosis preceded mycobacterium bovis and related species. whole-genome comparisons show that members ...201121672667
attenuated but live: a pelvic abscess caused by bacille calmette-guerin. 201121670115
long-term molecular surveillance of multidrug-resistant tuberculosis in spain.the data presented here span 11years (1998-2008) of monitoring of multidrug-resistant tuberculosis (mdr-tb) clustering through molecular typing techniques in spain. the molecular and epidemiological data of 480 multidrug-resistant mycobacterium tuberculosis complex isolates were analyzed. thirty-one clusters involving 157 (32.7%) patients were identified. the proportion of immigrants increased substantially over the study period reaching 65% in 2008; however, the clustering rate remained stable ...201121669301
influence of previous tuberculin skin test on serial ifn-╬│ release assays.tuberculin skin test (tst) and interferon-╬│ release assays (igras) have been proposed for serial testing in tuberculosis. in the present study, we assessed the effect of tst on subsequent quantiferon-tb gold in-tube (qft-git) results by monitoring the evolution of responses during a follow-up period of 6 weeks. one hundred and two subjects were initially tested with qft-git and subsequently with tst; then the qft-git was performed serially 1, 2, 4, and 6 weeks after the tst. a subgroup of 40 su ...201121664872
antimycobacterial and synergistic effects of 18β-glycyrrhetinic acid or glycyrrhetinic acid-30-piperazine in combination with isoniazid, rifampicin or streptomycin against mycobacterium bovis.18ß-glycyrrhetinic acid (18ßga) is a major bioactive component of liquorice with known activity. in this study, we found that both 18ßga and its derivative glycyrrhetinic acid-30-piperazine (pga), have potent antimycobacterial properties against the drug-susceptible and drug-resistant mycobacterium bovis. more importantly, they exhibited synergistic effects with the first-line drugs isoniazid (inh), rifampicin (rif) and streptomycin (sm) against clinical m. bovis isolates, including drug-resista ...201121656601
overt mycobacterium avium subsp. paratuberculosis infection: an infrequent occurrence in archived tissue from false tb reactor cattle in michigan, usa.the objective of this study was to retrospectively determine whether or not cattle from the state of michigan which were classified as bovine tuberculosis reactors, based on currently approved field and laboratory testing methods, were overtly infected with mycobacterium avium subsp. paratuberculosis (map). included in this study were 384 adult cattle submitted to the diagnostic center for population and animal health over a seven-year period. cattle were tested utilizing standard methods to con ...201121647343
bovine tuberculosis and the establishment of an eradication program in the united states: role of veterinarians.the significance of the identification of mycobacterium bovis as a zoonotic pathogen in 1882 was not initially recognized. after years of research by veterinarians, and other scientists, the importance of m. bovis as a pathogen and the public health ramifications, were appreciated. veterinarians played pivotal roles in the creation of improved meat and milk inspection, diagnosis of m. bovis infected cattle, and in time, a bovine tuberculosis eradication program that would impact every cattle pro ...201121647341
relative efficacy of uptake and presentation of bcg antigens by type i mouse lung epithelial cells and peritoneal macrophages.flow cytometric studies indicated that both peritoneal macrophages (pms) and primary lung epithelial (ple) cells isolated from mouse lung could take up fluorescence tagged bcg. bcg uptake in both cases was significantly inhibited by cytochalasin d indicating active internalization of bcg by these cells. confocal microscopy data further confirmed that bcg was internalized by ple cells. bcg sonicate antigen (sbcg) had marked toxicity towards pms but were relatively non-toxic to ple cells. accordin ...201121646448
post-mortem examination and laboratory-based analysis for the diagnosis of bovine tuberculosis among dairy cattle in ecuador.veterinary inspection in slaughterhouses allows for the detection of macroscopic lesions reminiscent of bovine tuberculosis, but the presence of mycobacterium bovis must be confirmed by laboratory methods. this study aimed at comparing the performances of the standard diagnostic tools used to identify m. bovis in tissue specimens sampled from suspicious animals. during a two years period, 1390 cattle were inspected at the machachi abattoir in the mejia canton - ecuador. a total of 33 animals wit ...201121645934
evidence for genetic variance in resistance to tuberculosis in great britain and irish holstein-friesian populations.here, we jointly summarise scientific evidence for genetic variation in resistance to infection with mycobacterium bovis, the primary agent of bovine tuberculosis (tb), provided by two recent and separate studies of holstein-friesian dairy cow populations in great britain (gb) and ireland.201121645294
lack of correlation between bcg-induced tuberculin skin test sensitisation and protective immunity in cattle.vaccination of cattle with mycobacterium bovis bacille calmette-guérin (bcg) can provide significant protection against bovine tuberculosis (tb). however, bcg vaccination sensitises animals to respond to the tuberculin skin-test. this provides a potential operational impediment to the use of bcg as a cattle vaccine since the tuberculin skin-test is the primary surveillance tool used by many countries with 'test and slaughter' control strategies. currently, it is also unclear what bcg-induced ski ...201121640776
detection of pathogenic mycobacteria based on functionalized quantum dots coupled with immunomagnetic separation.mycobacteria have always proven difficult to identify due to their low growth rate and fastidious nature. therefore molecular biology and more recently nanotechnology, have been exploited from early on for the detection of these pathogens. here we present the first stage of development of an assay incorporating cadmium selenide quantum dots (qds) for the detection of mycobacterial surface antigens. the principle of the assay is the separation of bacterial cells using magnetic beads coupled with ...201121637746
inhibitory effect of cyclic trihydroxamate siderophore, desferrioxamine e, on the biofilm formation of mycobacterium species.formation of biofilm in pathogenic bacteria defends them from antibiotics and the immune system of a host's life. hence, investigation of the molecular mechanisms of biofilm formation and search for new substances counteracting this formation are becoming an attractive research area. in the course of our search for new inhibitors of biofilm formation in mycobacterium species, we rediscovered a cyclic trihydroxamate siderophore, desferrioxamine e, from the culture of the marine-derived actinomyce ...201121628895
endemic cattle diseases: comparative epidemiology and governance.cattle are infected by a community of endemic pathogens with different epidemiological properties that invoke different managerial and governmental responses. we present characteristics of pathogens that influence their ability to persist in the uk, and describe a qualitative framework of factors that influence the political response to a livestock disease. we develop simple transmission models for three pathogens (bovine viral diarrhoea virus, bovine herpesvirus and mycobacterium avium spp. par ...201121624918
interaction of n-methyl-2-alkenyl-4-quinolones with atp-dependent mure ligase of mycobacterium tuberculosis: antibacterial activity, molecular docking and inhibition kinetics.objectives the aim of this study was to comprehensively evaluate the antibacterial activity and mure inhibition of a set of n-methyl-2-alkenyl-4-quinolones found to inhibit the growth of fast-growing mycobacteria. methods using the spot culture growth inhibition assay, mics were determined for mycobacterium tuberculosis h(37)rv, mycobacterium bovis bcg and mycobacterium smegmatis mc(2)155. mics were determined for mycobacterium fortuitum, mycobacterium phlei, methicillin-resistant staphylococcus ...201121622974
incubation of whole blood at 39{degrees}c augments ip-10 and ifn-{gamma} responses to m. tuberculosis antigens.background a rarely challenged dogma in cell mediated immune-assays (cmi) is the incubation temperature 37°c. fever augments pro-inflammatory immune responses in-vivo and the aim of this study was to explore whether incubation at fever-range temperature could increase antigen-specific biomarker responses. materials and methods we compared cmi responses following incubation of whole blood at 37°c and 39°c from 1) 34 healthy subjects incubated with the antigen tb10.4 present in the bacille calmett ...201121613464
infection of eurasian badgers (meles meles) with mycobacterium bovis and mycobacterium avium complex in spain.the prevalence, distribution and pathology related to infection with mycobacterium bovis and other mycobacteria were determined in trapped (n=36) and road-killed (n=121) badgers in spain from 2006 to 2010. the prevalence of m. bovis based on bacteriological culture from road-killed badgers was 8/121 (6.6%) and from trapped badgers was 0/36 (0%). tuberculosis/m. bovis infection was evident in 15/121 (12.4%) road-killed badgers when bacteriology and histopathology were combined. mycobacterium aviu ...201121612958
another step down the development pipeline for the novel tuberculosis vaccine mva-85a. 201121606528
dual neonate vaccine platform against hiv-1 and m. tuberculosis.acquired immunodeficiency syndrome and tuberculosis (tb) are two of the world's most devastating diseases. the first vaccine the majority of infants born in africa receive is mycobacterium bovis bacillus calmette-guérin (bcg) as a prevention against tb. bcg protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary tb and enhancing boost delivered by recombinant modified vaccinia virus ankara (rmva) expressing antigen 85a (ag85a) of ...201121603645
intravital imaging reveals limited antigen presentation and t cell effector function in mycobacterial granulomas.cell-mediated adaptive immunity is critical for host defense, but little is known about t cell behavior during delivery of effector function. here we investigate relationships among antigen presentation, t cell motility, and local production of effector cytokines by cd4(+) t cells within hepatic granulomas triggered by bacille calmette-guérin or mycobacterium tuberculosis. at steady-state, only small fractions of mycobacteria-specific t cells showed antigen-induced migration arrest within granul ...201121596592
preface. 201121596494
evaluation of the microscopic observation drug susceptibility assay for detection of mycobacterium tuberculosis resistance to pyrazinamide.clin microbiol infect abstract: the microscopic observation drug susceptibility assay (mods) was evaluated to determine susceptibility to pyrazinamide in mycobacterium tuberculosis, and compared with the broth microdilution method (bmm), absolute concentration method (acm), and pyrazinamidase (pzase) determination. we tested 34 m. tuberculosis clinical isolates (24 sensitive and eight resistant to pyrazinamide) and the control strains m. tuberculosis h37rv (atcc 27294) and mycobacterium bovis an ...201121595790
glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs.dynamic changes in the lipid composition of the cell wall occur in pathogenic mycobacteria that are often intended for adaptation to the host environment. dormant mycobacteria should have evolved efficient maneuvers for cohabitation, allowing the microbes to persist for years within the host. glycerol monomycolate (gromm) has been implicated as a specific immune target in human individuals with latent, but not active, tuberculosis, but the in vivo response to gromm and the relevance of it to lat ...201121575604
european 1: a globally important clonal complex of mycobacterium bovis.we have identified a globally important clonal complex of mycobacterium bovis by deletion analysis of over one thousand strains from over 30 countries. we initially show that over 99% of the strains of m. bovis, the cause of bovine tuberculosis, isolated from cattle in the republic of ireland and the uk are closely related and are members of a single clonal complex marked by the deletion of chromosomal region rdeu1 and we named this clonal complex european 1 (eu1). eu1 strains were present at le ...201121571099
antimycobacterial evaluation and preliminary phytochemical investigation of selected medicinal plants traditionally used in mozambique.ethnopharmacological relevance: several medicinal plants are traditionally used in mozambique to treat tuberculosis and related symptoms. aims of the study: it was aimed to assess the in vitro antimycobacterial activity of crude extracts from fifteen medicinal plants and to reveal main classes of compounds which may account for the activity of extracts. methods and materials: the plant materials were sequentially extracted by n-hexane, dichloromethane, ethyl acetate, and 70% ethanol. decoction o ...201121571059
effects of mycobacterium bovis on monocyte-derived macrophages from bovine tuberculosis infection and healthy cattle.bovine tuberculosis (btb) is a chronic infectious disease caused by the pathogen mycobacterium bovis and poses a long-standing threat to livestock worldwide. to further elucidate the poorly defined btb immune response in cattle, we utilized monocyte-derived macrophages (mdms) to assess the gene expression related to m. bovis beijing strain stimulation. here, we demonstrate the existence of distinctive gene expression patterns between macrophages of healthy cattle and those exposed to btb. in com ...201121569079
evaluation of two mutants of mycobacterium avium subsp. paratuberculosis as candidates for a live attenuated vaccine for johne's disease.control of johne's disease, caused by mycobacterium avium subsp. paratuberculosis, has been difficult because of a lack of an effective vaccine. to address this problem we used targeted gene disruption to develop candidate mutants with impaired capacity to survive ex vivo and in vivo to test as a vaccine. we selected rela and pkng, genes known to be important virulence factors in mycobacterium tuberculosis and mycobacterium bovis, for initial studies. deletion mutants were made in a wild type ma ...201121565243
overexpression of rv3097c in mycobacterium bovis bcg abolished the efficacy of bcg vaccine to protect against mycobacterium tuberculosis infection in mice.rv3097c of mycobacterium tuberculosis encoding lipase (lipy) was overexpressed in mycobacterium bovis bcg. efficacy of recombinant bcg to protect against infection of m. tuberculosis was evaluated in mice. whereas the parent bcg vaccine protected the mice against infection, recombinant bcg overexpressing lipy offered no protection as judged by viable counts of tubercule bacilli in lungs, weight of infected mice, pathology of lungs and survival of challenged mice. downregulation of overexpression ...201121565242
modification of the quantiferon-tb gold (in-tube) assay for the diagnosis of mycobacterium bovis infection in african buffaloes (syncerus caffer).african buffaloes (syncerus caffer) are the most significant wildlife maintenance hosts of mycobacterium bovis, the causative organism of bovine tuberculosis (btb). current diagnostic tests for the detection of m. bovis infection in free-ranging buffaloes have numerous limitations and we wished to evaluate a modification to a human tb assay, the quantiferon-tb gold (in-tube) assay (qft), as a practical diagnostic test for btb in buffaloes. one hundred and seventy-five buffaloes were tested using ...201121561669
[a case with severe combined immunodeficiency diagnosed with disseminated bcg infection by detecting specific rd gene deletion].because the bacillus calmette-guérin (bcg) prevents infants from contracting miliary tuberculosis and tuberculosis meningitis, bcg vaccination is recommended for those under 6 months old in japan. complications such as favorable local inflammatory reactions including redness, induration, and abscess formation may occur, but severe adverse effects such as osteomyelitis, periostitis, and disseminated bcg infection are generally rare. we report an 11-month-old boy with severe combined immunodeficie ...201121560422
fiber optic microendoscopy for preclinical study of bacterial infection dynamics.we explore the use of fiber optic microendoscopy to image and quantify bacterial infection in the skin and lungs using an animal model. the contact probe fiber bundle fluorescence microendoscope has a 4 µm resolution, a 750 µm field of view, and a 1 mm outer diameter. subcutaneous and intra-tracheal infections of fluorescent mycobacterium bovis bacillus calmette-guérin (bcg) bacteria were detected in situ from inocula down to 10(4) and 10(7) colony forming units, respectively.201121559125
[phenotypic analysis of bcg-specific effector memory cd4(+); t cells in pbmcs by eight-color flow cytometry.]aim: to evaluate cytokine production and subsets in pbmcs from ppd+ normal donors after stimulation with bcg. methods: pbmcs were isolated from ppd+ normal individuals, and cytokine production and bcg-specific t cell subsets were assessed by eight-color flow cytometry. results: following stimulation with bcg, cd4(+); but not cd8(+); t cells expressed ifn-γ, il-2 and tnf-α. phenotypic analysis indicated that cytokine-producing cells were cd4(+);cd45ro(+);cd62l(-);cd27(-); and cd4(+);cd45ro(+);cd6 ...201121557902
a family of ifn-gamma-inducible 65-kd gtpases protects against bacterial infection.immune interferon gamma (ifn-γ) is essential for mammalian host defense against intracellular pathogens. ifn-γ induces nearly 2000 host genes, yet few have any assigned function. here, we examined a complete mouse 65-kilodalton (kd) guanylate-binding protein (gbp) gene family as part of a 43-member ifn-γ-inducible guanosine triphosphatase (gtpase) superfamily in mouse and human genomes. family-wide loss-of-function analysis found that at least four gbps--gbp1, gbp6, gbp7, and gbp10--conferred ce ...201121551061
a new experimental infection model in ferrets based on aerosolised mycobacterium bovis.there is significant interest in developing vaccines to control bovine tuberculosis, especially in wildlife species where this disease continues to persist in reservoir species such as the european badger (meles meles). however, gaining access to populations of badgers (protected under uk law) is problematic and not always possible. in this study, a new infection model has been developed in ferrets (mustela furo), a species which is closely related to the badger. groups of ferrets were infected ...201121547237
mycobacterium bovis in swine: spoligotyping of isolates from argentina.a total of 143 mycobacterium bovis isolates of pigs, from the most productive swine area in argentina, were typed by spoligotyping. twenty-two different spoligotypes were identified, and 133 (93%) isolates were grouped into 12 clusters. one of them, designed sb0140, was the most frequent because it held 83 (58%) isolates. this spoligotype also grouped 362 (43%) out of 841 isolates from previously typed cattle and, thus, constitutes the most frequent in our country. in addition, 135 (94%) isolate ...201121547236
bovine tuberculosis in a nebraska herd of farmed elk and fallow deer: a failure of the tuberculin skin test and opportunities for serodiagnosis.in 2009, mycobacterium bovis infection was detected in a herd of 60 elk (cervus elaphus) and 50 fallow deer (dama dama) in nebraska, usa. upon depopulation of the herd, the prevalence of bovine tuberculosis (tb) was estimated at ∼71-75%, based upon histopathology and culture results. particularly with elk, gross lesions were often severe and extensive. one year ago, the majority of the elk had been tested for tb by single cervical test (sct), and all were negative. after initial detection of a t ...201121547234
a study of the persistence of mycobacterium bovis in the environment under natural weather conditions in michigan, usa.reisolation of mycobacterium bovis from inoculated substrates was used to follow the persistence of viable m. bovis bacteria exposed to natural weather conditions over a 12-month period. environmental factors were recorded continuously, and factors affecting m. bovis persistence (i.e., temperature, season, and substrate) were studied using survival analysis and cox's proportional hazards regression. persistence of m. bovis in the environment was significantly shorter in the spring/summer season, ...201121547222
perspectives on the history of bovine tb and the role of tuberculin in bovine tb eradication.tuberculosis remains a significant disease of animals and humans worldwide. bovine tuberculosis is caused by mycobacteria with an extremely wide host range and serious, although currently probably underdiagnosed, zoonotic potential. where bovine tuberculosis controls are effective, human zoonotic tb, due to mycobacterium bovis or m. caprae, is uncommon and clinical cases are infrequent in cattle. therefore, the control and ultimate eradication of bovine tuberculosis is desirable. tuberculin test ...201121547209
assessment of in vivo and in vitro tuberculosis diagnostic tests in mycobacterium caprae naturally infected caprine flocks.caprine tuberculosis in spain is mainly caused by mycobacterium caprae although the progression of the disease and lesion severity is similar to that caused by mycobacterium bovis. in this study, the sensitivity of the gamma-interferon (ifn-γ) assay using an antigen cocktail containing early secretory antigenic target-6kda (esat-6) and culture filtrate protein 10 (cfp-10) peptides for stimulation was determined and compared with those obtained in single intradermal tuberculin (sit) and single in ...201121546104
the in vivo immunomodulatory effect of recombinant tumour necrosis factor-alpha in guinea pigs vaccinated with mycobacterium bovis bacille calmette-guérin.previous studies from our laboratory demonstrated that treatment in vitro with recombinant guinea pig tumour necrosis factor tnf (rgptnf)-α-enhanced t cell and macrophage functions. similarly, injection of mycobacterium tuberculosis-infected guinea pigs with anti-tnf-α altered splenic granuloma organization and caused inflammatory changes and reduced the cell-associated mycobacteria in the tuberculous pluritis model. in this study, rgptnf-α was injected into bacille calmette-guérin (bcg)-vaccina ...201121545584
knockout mutation of p27-p55 operon severely reduces replication of mycobacterium bovis in a macrophagic cell line and survival in a mouse model of infection.integrity of p27-p55 operon has been demonstrated to be crucial for replication of mycobacterium tuberculosis, the main agent of human tuberculosis, in the mouse model of infection. however, the individual contribution of each gene of the operon for the virulence of pathogenic mycobacterium spp. still remains unclear. the operon is formed by two genes, p27 and p55. p27 gene encodes a lipoprotein that binds triacylated glycolipids and modulates the host immune responses by inhibiting the mhc-ii a ...201121543883
mechanical disruption of lysis-resistant bacteria using a miniature, low power, disposable device.molecular detection of microorganisms requires microbial cell disruption to release nucleic acids. sensitive detection of thick-walled microorganisms such as bacillus spores and mycobacterium cells typically necessitates mechanical disruption through bead beating or sonication, using benchtop instruments that require line power. miniaturized, low power, battery operated devices are needed to facilitate mechanical pathogen disruption for nucleic acid testing at the point of care and in field sett ...201121543569
latency antigen α-crystallin based vaccination imparts a robust protection against tb by modulating the dynamics of pulmonary cytokines.efficient control of tuberculosis (tb) requires development of strategies that can enhance efficacy of the existing vaccine mycobacterium bovis bacille calmette guerin (bcg). to date only a few studies have explored the potential of latency-associated antigens to augment the immunogenicity of bcg.201121533158
tuberculosis in goats on a farm in ireland: epidemiological investigation and control.this paper describes an outbreak of tuberculosis (tb) caused by mycobacterium bovis in a dairy goat herd on a farm in ireland, where 66.3 per cent of the herd tested positive to the single intradermal comparative tuberculin test (sictt) at initial detection. an epidemiological investigation was conducted to determine the origin of the outbreak, considering issues such as animal movements and herd management practices. infection was introduced with a consignment of goats, as determined by the var ...201121527475
a novel strategy to screen bacillus calmette-guérin protein antigen recognized by γδ tcr.phosphoantigen was originally identified as the main γδ tcr-recognized antigen that could activate γδ t cells to promote immune protection against mycobacterial infection. however, new evidence shows that the γδ t cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. in contrast, whole lysates of mycobacterium could activate immune protection more potently, implying that other γδ tcr-recognized antigens that elicit protective immune respons ...201121526117
interleukin-17a differentially modulates bcg induction of cytokine production in human blood macrophages.the pathogenesis of mtb depends in part on cytokine cross-regulation between macrophages and t cells in host immunity. th17 cells produce il-17a to induce granuloma formation and to restrict mycobacterial dissemination. il-17a also mediates cytokine responses induced by proinflammatory cytokines such as tnf-α. our previous results showed that bcg induces il-6, il-10, and tnf-α via activity of protein kinases, including dsrna-activated serine/threonine protein kinase and glycogen synthase kinase- ...201121521755
effects of cefodizime on chemokines of liver tissues in mice with immunological hepatic injury.chronic hepatic inflammation is characterized by the accumulation of lymphocytes as a consequence of increased recruitment from the blood and retention within the tissue at sites of infection. cxc chemokine ligand 16 (cxcl16) mrna has been detected in both inflamed and normal liver tissues and is strongly upregulated in the injured liver tissues in a murine model. the aim of this study was to investigate the effect of cefodizime on cxcl16 mrna of liver tissues in mice with immunological hepatic ...201121518570
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