Articoli di riviste: "Mycobacterium bovis"

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KRYSZTOPA-GRZYBOWSKA, KATARZYNA, SYLWIA BRZEZIŃSKA, EWA AUGUSTYNOWICZ-KOPEĆ, EWA AUGUSTYNOWICZ e ANNA LUTYŃSKA. "PCR-Based Genomic Deletion Analysis of RD-Regions in the Identification of Mycobacteria Isolated from Adverse Events Following BCG Vaccination or TB Suspected Cases". Polish Journal of Microbiology 63, n. 3 (2014): 359–62. http://dx.doi.org/10.33073/pjm-2014-048.

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Early identification of mycobacterial species is crucial for early diagnosis. PCR-multiplex method performed on randomly chosen 54 mycobacteria isolates originating from clinical samples was found to be an inexpensive, quick and reliable alternative for commercially available diagnostics tests. Although the results of gene probes identification performed by NTLDR were generally consistent with multiplex PCR, two mixed Mycobacterium bovis BCG/Mycobacterium tuberculosis infections and a single misdiagnosis of M. tuberculosis with M. bovis were found. The routine application of multiplex-PCR has the potential to make diagnostics surveillance studies feasible.

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Waters, W. R., B. J. Nonnecke, M. V. Palmer, S. Robbe-Austermann, J. P. Bannantine, J. R. Stabel, D. L. Whipple et al. "Use of Recombinant ESAT-6:CFP-10 Fusion Protein for Differentiation of Infections of Cattle by Mycobacterium bovis and by M. avium subsp. avium and M. avium subsp. paratuberculosis". Clinical Diagnostic Laboratory Immunology 11, n. 4 (luglio 2004): 729–35. http://dx.doi.org/10.1128/cdli.11.4.729-735.2004.

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ABSTRACT Immunological diagnosis of Mycobacterium bovis infection of cattle is often confounded by cross-reactive responses resulting from exposure to other mycobacterial species, especially Mycobacterium avium. Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are dominant gamma interferon (IFN-γ)-inducing antigens of tuberculous mycobacteria, and they are absent from many environmental nontuberculous mycobacteria. Because M. avium exposure is the primary confounding factor in the diagnosis of M. bovis-infected animals, in vitro responses to a recombinant ESAT-6:CFP-10 (rESAT-6:CFP-10) fusion protein by blood leukocytes from cattle naturally exposed to M. avium or experimentally challenged with Mycobacterium avium subsp. avium or Mycobacterium avium subsp. paratuberculosis were compared to responses by M. bovis-infected cattle. Responses to heterogeneous mycobacterial antigens (i.e., purified protein derivatives [PPDs] and whole-cell sonicates [WCSs]) were also evaluated. Tumor necrosis factor alpha (TNF-α), IFN-γ, and nitric oxide responses by M. bovis-infected cattle to rESAT-6:CFP-10 exceeded (P < 0.05) the corresponding responses by cattle naturally sensitized to M. avium. Experimental infection with M. bovis, M. avium, or M. avium subsp. paratuberculosis induced significant (P < 0.05) IFN-γ and nitric oxide production to WCS and PPD antigens, regardless of the mycobacterial species used for the preparation of the antigen. Responses to homologous crude antigens generally exceeded responses to heterologous antigens. Nitric oxide and IFN-γ responses to rESAT-6:CFP-10 by blood leukocytes from M. bovis-infected calves exceeded (P < 0.05) the corresponding responses of noninfected, M. avium-infected, and M. avium subsp. paratuberculosis-infected calves. Despite the reported potential for secretion of immunogenic ESAT-6 and CFP-10 proteins by M. avium and M. avium subsp. paratuberculosis, it appears that use of the rESAT-6:CFP-10 fusion protein will be useful for the detection of tuberculous cattle in herds with pre-existing sensitization to M. avium and/or M. avium subsp. paratuberculosis.

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Waters, W. R., A. O. Whelan, K. P. Lyashchenko, R. Greenwald, M. V. Palmer, B. N. Harris, R. G. Hewinson e H. M. Vordermeier. "Immune Responses in Cattle Inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii". Clinical and Vaccine Immunology 17, n. 2 (9 dicembre 2009): 247–52. http://dx.doi.org/10.1128/cvi.00442-09.

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ABSTRACT Cattle were inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii to compare the antigen-specific immune responses to various patterns of mycobacterial disease. Disease expression ranged from colonization with associated pathology (M. bovis infection) and colonization without pathology (M. tuberculosis infection) to no colonization or pathology (M. kansasii infection). Delayed-type hypersensitivity and gamma interferon responses were elicited by each mycobacterial inoculation; however, the responses by the M. bovis- and M. tuberculosis-inoculated animals exceeded those of the M. kansasii-inoculated animals. Specific antibody responses were detected in all M. tuberculosis- and M. bovis-inoculated cattle 3 weeks after inoculation. From 6 to 16 weeks after M. tuberculosis inoculation, the antibody responses waned, whereas the responses persisted with M. bovis infection. With M. kansasii inoculation, initial early antibody responses waned by 10 weeks after inoculation and then increased 2 weeks after the injection of purified protein derivative for the skin test at 18 weeks after challenge. These findings indicate that antibody responses are associated with the antigen burden rather than the pathology, cellular immune responses to tuberculin correlate with infection but not necessarily with the pathology or bacterial burden, and exposure to mycobacterial antigens may elicit an antibody response in a presensitized animal.

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Aldwell, Frank E., Bridget L. Dicker, Fernanda M. Da Silva Tatley, Martin F. Cross, Simon Liggett, Colin G. Mackintosh e J. Frank T. Griffin. "Mycobacterium bovis-Infected Cervine Alveolar Macrophages Secrete Lymphoreactive Lipid Antigens". Infection and Immunity 68, n. 12 (1 dicembre 2000): 7003–9. http://dx.doi.org/10.1128/iai.68.12.7003-7009.2000.

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ABSTRACT Tuberculosis is caused by intracellular bacteria belonging to the genus Mycobacterium, including M. tuberculosisand M. bovis. Alveolar macrophages (AMs) are the primary host cell for inhaled mycobacteria. However, little is known about the mechanisms by which infected AMs can process and present mycobacterial antigens to primed lymphocytes and how these responses may affect ensuing protection in the host. In the present study, we sought to determine whether AMs from a naturally susceptible host forMycobacterium bovis (red deer) could produce and secrete soluble immunoreactive antigens following mycobacterial infection in vitro. Confluent monolayers of deer AMs were infected with either heat-killed or live virulent M. bovis or M. bovis BCG at a multiplicity of infection of 5:1 and cultured for 48 h. Culture supernatants were collected, concentrated, and tested for the presence of mycobacterial antigens in a lymphocyte proliferation assay by using peripheral blood mononuclear cells fromM. bovis-sensitized or naive deer. Supernatants derived from macrophages which had been infected with live bacilli stimulated the proliferation of antigen-sensitized, but not naive, lymphocytes. Supernatants derived from uninoculated AMs or AMs inoculated with heat-killed bacilli failed to stimulate lymphocyte proliferation. The lymphoproliferative activity was retained following lipid extraction of the supernatants, which were free of amino groups as determined by thin-layer chromatography. These results demonstrate that mycobacteria which are actively growing within AMs produce lipids which are secreted into the extracellular milieu and that these lipids are recognized by lymphocytes from mycobacterium-primed hosts. We suggest that mycobacterial lipids are released from AMs following aerosol infection in vivo and that they play an important role in the early immune response to tuberculosis.

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Ekladious, Adel. "Disseminated Mycobacterium Bovis". International Journal of Clinical Case Reports and Reviews 11, n. 4 (21 luglio 2022): 01–03. http://dx.doi.org/10.31579/2690-4861/232.

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Intravesical BacillusChalmette- Guerin (BCG) still a popular medication for non-invasive bladdercancer in the low-income country, one of the uncommon side effects is disseminated Mycobacterium Bovis. We present a patient who presented with haematuria, diagnosed as urothelial superficial bladder cancer, treated with incomplete resectionand intravesical BCG, 6 months after treatment, he presented with increasing shortness of breath, headache and abdominal pain, diagnosed as tuberculous, meningitis, massive pleural effusion, granulomatous hepatitis he responded very well to anti tuberculous treatment.

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Stern, Rebecca, Clay Roscoe e Elizabeth A. Misch. "<i>Mycobacterium bovis</i> BCG osteoarticular infection complicating immune therapy for bladder cancer: a case report". Journal of Bone and Joint Infection 6, n. 4 (22 febbraio 2021): 107–10. http://dx.doi.org/10.5194/jbji-6-107-2021.

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Abstract. Osteoarticular infection with Mycobacterium bovis (M. bovis) is a rare complication of bladder cancer treatment with intravesical Bacillus Calmette–Guèrin (BCG). We describe a case of disseminated Mycobacterium bovis BCG infection masquerading as a chronic prosthetic joint infection in a patient with several risk factors for progressive mycobacterial infection.

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Erb, Klaus J., Claudia Trujillo, Mike Fugate e Heidrun Moll. "Infection with the Helminth Nippostrongylus brasiliensis Does Not Interfere with Efficient Elimination of Mycobacterium bovis BCG from the Lungs of Mice". Clinical and Vaccine Immunology 9, n. 3 (maggio 2002): 727–30. http://dx.doi.org/10.1128/cdli.9.3.727-730.2002.

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ABSTRACT Infection with Mycobacterium tuberculosis continues to be one of the major global health threats. Strong mycobacterium-specific Th1 immune responses correlate with protection, and decreased Th1 responses correlate with disease progression. In contrast, the impact of Th2 responses on the development of protective immune responses to mycobacteria remains unclear. To analyze whether ongoing Th2 responses present in the lung influence the development of a protective Th1 immune response to mycobacteria, we coinfected mice with the helminth Nippostrongylus brasiliensis and Mycobacterium bovis BCG. We found that the T cells from the lymph nodes of coinfected mice secreted significantly less gamma interferon than did the T cells from mice infected with M. bovis BCG after in vitro stimulation with purified protein from M. tuberculosis when 108 CFU of M. bovis BCG were used for the infection. This result indicates that the helminth infection reduced the Th1 immune response to the mycobacteria in the lung. However, mycobacterial clearance was not delayed in the coinfected animals. Importantly, the infection with BCG after the helminth infection did not reduce the helminth-induced Th2 response in the lung, ruling out the possibility that the lack of a reduction in bacterial clearance in the coinfected mice was due to a downmodulation of the helminth-induced Th2 response. Taken together, our results suggest that ongoing Th2 responses in the lung do not necessarily lead to increased susceptibility to mycobacterial infection.

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Da Silva Pedroso, Silvia Cristina, Karla Valéria Batista Lima, Ismari Perini Furlaneto, Yan Corrêa Rodrigues, Darlene Kássia Saraiva Queiroz Pantoja, Alex Junior Souza de Souza e Washington Luiz Assunção Pereira. "Bovine tuberculosis due to Mycobacterium bovis and other mycobacteria among water buffalo (Bubalus bubalis) from the Brazilian Amazon". Journal of Infection in Developing Countries 15, n. 05 (31 maggio 2021): 736–41. http://dx.doi.org/10.3855/jidc.13558.

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Introduction: Zoonotic tuberculosis is a disease of public health importance worldwide, especially in developing countries. The present study aimed to investigate the role played by Mycobacterium bovis and other mycobacteria as etiologic agents of bubaline tuberculosis (TB) in the Brazilian Amazon region. Methodology: Granulomatous lesions suggestive of TB obtained from 109 buffaloes (n =109) during sanitary inspection at slaughter were subjected to histopathological evaluation, immunohistochemical (IHC) detection of Mycobacterium antigens, and to molecular tests (PCR) to detect hsp65, IS6110 and RD4 genes, which are specific to Mycobacterium spp., Mycobacterium tuberculosis Complex (MTBC) and M. bovis, respectively. Results: PCR results indicated Mycobacterium infection in 87.2% of the cases, of which 69.5% were positive for M. bovis, 27.4% belonged to MTBC, and 3.1% were probably non-TB mycobacteria. There was good agreement between the genus-specific molecular technique and the histopathological analysis. This high frequency of TB cases caused by non-M. bovis suggests a diversified scenario of mycobacteria associated with bubaline TB in the Brazilian Amazon region. Conclusions: The results reinforce the need of discussing the inclusion of more accurate techniques in examinations carried out by Inspection Services in Brazil.

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Gobin, Jovana, Diane K. Wong, Bradford W. Gibson e Marcus A. Horwitz. "Characterization of Exochelins of theMycobacterium bovis Type Strain and BCG Substrains". Infection and Immunity 67, n. 4 (1 aprile 1999): 2035–39. http://dx.doi.org/10.1128/iai.67.4.2035-2039.1999.

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ABSTRACT Pathogenic mycobacteria must acquire iron in the host in order to multiply and cause disease. To do so, they release abundant quantities of siderophores called exochelins, which have the capacity to scavenge iron from host iron-binding proteins and deliver it to the mycobacteria. In this study, we have characterized the exochelins of Mycobacterium bovis, the causative agent of bovine and occasionally of human tuberculosis, and the highly attenuated descendant of M. bovis, bacillus Calmette-Guérin (BCG), widely used as a vaccine against human tuberculosis. The M. bovis type strain, five substrains ofM. bovis BCG (Copenhagen, Glaxo, Japanese, Pasteur, and Tice), and two strains of virulent Mycobacterium tuberculosis all produce the same set of exochelins, although the relative amounts of individual exochelins may differ. Among these mycobacteria, the total amount of exochelins produced is greatest in M. tuberculosis, intermediate in M. bovis, and smallest in M. bovis BCG.

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DIDKOWSKA, ANNA, PIOTR ŻMUDA, BLANKA ORŁOWSKA e KRZYSZTOF ANUSZ. "Mycobacterial infections in cats (Felis catus) as a potential threat to humans – a review 2014–2023". Medycyna Weterynaryjna 79, n. 12 (2023): 6842–2023. http://dx.doi.org/10.21521/mw.6842.

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Mycobacteria infections in cats include tuberculosis (caused by Mycobacterium bovis and Mycobacterium microti) and mycobacteriosis caused by non-tuberculous mycobacteria (NTM). The aim of the paper is to present the latest reports on mycobacterial infections in cats and place emphasis on their impact on the health of their owners. The reviewers looked for papers about mycobacterial infections in cats in PubMed and Google Scholar from any date from January 2014 to June 2023. The search used the following keywords: cat, feline, tuberculosis, and mycobacteria. Papers were evaluated for their value to science and their applicability. Papers published in recent years have shown that mycobacterial infections in cats should still be considered in a differential diagnosis when many clinical signs present and they are mainly skin and ocular symptoms. An epidemiological investigation of these infections is highly important because cases were reported also in low-risk regions. Mycobacterial infections pose a risk to humans. The degree of risk depends on many factors, such as the species of mycobacteria, the closeness of animal-owner contact, and the immune status of the owner. The greatest risk are still believed to be M. bovis infections; however, NTM infections should also raise a concern, especially in high-risk groups.

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Savova-Lalkovska, Tanya, Violeta Valcheva, Albena Dimitrova, Hristo Najdenski e Magdalena Bonovska. "Advantages of Real-time PCR and RD4-PCR as Molecular Methods for Rapid Detection of Bovine Tuberculosis in Bulgaria". Proceedings of the Bulgarian Academy of Sciences 75, n. 11 (30 novembre 2022): 1696–704. http://dx.doi.org/10.7546/crabs.2022.11.18.

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Representatives of Mycobacterium tuberculosis complex (MTBC) are potential causative agents of tuberculosis in animals and humans, and Mycobacterium bovis is considered a major one among domestic and wild ruminants. In the last twenty years, the role of another representative of MTBC – Mycobacterium caprae, has been proven in the countries of Central and Southern Europe. Study sample included 121 diagnostic materials from lymph nodes and lungs from cattle, positively and doubtfully PPD tuberculin-reacted, originating from 6 farms belonging to the 4 regions in Northern and Southern Bulgaria. The bacteriological examination showed typical growth for mycobacteria for 110 (90.9%) samples, which was confirmed by qPCR. By RD4-PCR we proved that 102 (92.7%) of the mycobacterial strains were M. caprae and the remaining 8 strains (7.3%) were M. bovis. This defines M. caprae as a dominant species in the etiology of tuberculosis in cattle in Bulgaria. In conclusion, we confirmed that the application of real-time PCR is an accurate and convenient method for rapid detection of M. bovis from cattle in the Bulgarian settings. RD4-PCR provides a sufficiently high differentiation and can be used for first-line typing of M. bovis isolates in Bulgaria. This proves the need for the simultaneous application of both methods in the diagnosis of bovine tuberculosis in Bulgaria.

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Guerra-Maupome, Mariana, Michelle H. Larsen, Mitchell V. Palmer, Ray Waters e Jodi L. McGill. "Characterization of bovine γδ T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection". Journal of Immunology 198, n. 1_Supplement (1 maggio 2017): 131.17. http://dx.doi.org/10.4049/jimmunol.198.supp.131.17.

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Abstract Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. γδ T cells participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector phenotype and adaptive immune functions of mycobacterium-responsive γδ T cells. To date, the impact of age or M. bovis infection on bovine γδ T cells memory/effector phenotype remains unknown. In this study, we addressed the age-dependent changes of circulating γδ T cells, analyzed functional and phenotypic differences in memory and activation marker expression, and evaluated functional responses of M. bovis-specific γδ T cells following M. bovis Bacille Calmette-Guerin (BCG) vaccination or virulent M. bovis infection. As expected, aerosol vaccination and virulent infection induced robust mucosal and systemic M. bovis-specific γδ T cell proliferative responses. Analysis of peripheral blood γδ T cells indicated phenotypic differences based on the expression of CD27 and CD45R that could suggest distinct functional properties. Recall responses after in vitro stimulation with mycobacterial antigens showed that expression of CD27 is critical for the expansion of peripheral IFN-γ-producing γδ T-cells and suggest that the CD27+ subset may compose the mycobacterium-responsive γδ T cell compartment in calves responding to M. bovis vaccination or infection. The ability of γδ T cells to mount a robust response during mycobacterial infections supports the notion that vaccine-elicited γδ T cell immunity might prove beneficial. Therefore, defining correlates of protection based on this population can accelerate the development of novel vaccines against TB.

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Bhakta, Sanjib, Gurdyal S. Besra, Anna M. Upton, Tanya Parish, Carolyn Sholto-Douglas-Vernon, Kevin J. C. Gibson, Stuart Knutton et al. "Arylamine N-Acetyltransferase Is Required for Synthesis of Mycolic Acids and Complex Lipids in Mycobacterium bovis BCG and Represents a Novel Drug Target". Journal of Experimental Medicine 199, n. 9 (26 aprile 2004): 1191–99. http://dx.doi.org/10.1084/jem.20031956.

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Mycolic acids represent a major component of the unique cell wall of mycobacteria. Mycolic acid biosynthesis is inhibited by isoniazid, a key frontline antitubercular drug that is inactivated by mycobacterial and human arylamine N-acetyltransferase (NAT). We show that an in-frame deletion of Mycobacterium bovis BCG nat results in delayed entry into log phase, altered morphology, altered cell wall lipid composition, and increased intracellular killing by macrophages. In particular, deletion of nat perturbs biosynthesis of mycolic acids and their derivatives and increases susceptibility of M. bovis BCG to antibiotics that permeate the cell wall. Phenotypic traits are fully complemented by introduction of Mycobacterium tuberculosis nat. We infer from our findings that NAT is critical to normal mycolic acid synthesis and hence other derivative cell wall components and represents a novel target for antituberculosis therapy. In addition, this is the first report of an endogenous role for NAT in mycobacteria.

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Fritz, Christian, Silvia Maass, Andreas Kreft e Franz-Christoph Bange. "Dependence of Mycobacterium bovis BCG on Anaerobic Nitrate Reductase for Persistence Is Tissue Specific". Infection and Immunity 70, n. 1 (gennaio 2002): 286–91. http://dx.doi.org/10.1128/iai.70.1.286-291.2002.

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ABSTRACT Mycobacterium bovis BCG, the only presently available vaccine against tuberculosis, was obtained from virulent M. bovis after serial passages in vitro. The vaccine strain retained at least some of its original virulence, as it persists in immune-competent hosts and occasionally may cause fatal disease in immune-deficient hosts. Mycobacterial persistence in vivo is thought to depend on anaerobic metabolism, an apparent paradox since all mycobacteria are obligate aerobes. Here we report that M. bovis BCG lacking anaerobic nitrate reductase (NarGHJI), an enzyme essential for nitrate respiration, failed to persist in the lungs, liver, and kidneys of immune-competent (BALB/c) mice. In immune-deficient (SCID) mice, however, bacilli caused chronic infection despite disruption of narG, even if growth of the mutant was severely impaired in lungs, liver, and kidneys. Persistence and growth of BCG in the spleens of either mouse strain appeared largely unaffected by lack of anaerobic nitrate reductase, indicating that the role of the enzyme in pathogenesis is tissue specific. These data suggest first that anaerobic nitrate reduction is essential for metabolism of M. bovis BCG in immune-competent but not immune-deficient mice and second that its role in mycobacterial disease is tissue specific, both of which are observations with important implications for pathogenesis of mycobacteria and vaccine development.

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Jordao, L., M. Simoes, C. Bleck, G. Griffiths e E. Anes. "Characterization of Mycobacterium bovis Phagosome". Microscopy and Microanalysis 14, S3 (settembre 2008): 124–25. http://dx.doi.org/10.1017/s1431927608089629.

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Mycobacterium tuberculosis complex are among the most successful pathogens. Their success resides in the ability to interfere with intracellular traffic avoiding natural pathways of the phagosome maturation. Recently, mycobacteria escape from the phagosome to the cytosol was investigated as an alternative survival strategy. In this context we decided to determine the exact intracellular location of Mycobacterium bovis in different host macrophages and characterize the pathogen intracellular niche for survival. The main goal here was to characterize live vs dead M. bovis spp phagosome in different host macrophages. Macrophages infection, fluorescence and EM procedures were carried out as described previously.

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Mailaender, Claudia, Norbert Reiling, Harald Engelhardt, Stefan Bossmann, Stefan Ehlers e Michael Niederweis. "The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosis". Microbiology 150, n. 4 (1 aprile 2004): 853–64. http://dx.doi.org/10.1099/mic.0.26902-0.

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Porins mediate the diffusion of hydrophilic solutes across the outer membrane of mycobacteria, but the efficiency of this pathway is very low compared to Gram-negative bacteria. To examine the importance of porins in slow-growing mycobacteria, the major porin MspA of Mycobacterium smegmatis was expressed in Mycobacterium tuberculosis and Mycobacterium bovis. Approximately 20 and 35 MspA molecules per μm2 cell wall were observed in M. tuberculosis and M. bovis BCG, respectively, by electron microscopy and quantitative immunoblot experiments. Surface accessibility of MspA in M. tuberculosis was demonstrated by flow cytometry. Glucose uptake was twofold faster, indicating that the outer membrane permeability of M. bovis BCG to small and hydrophilic solutes was increased by MspA. This significantly accelerated the growth of M. bovis BCG, identifying very slow nutrient uptake as one of the determinants of slow growth in mycobacteria. The susceptibility of both M. bovis BCG and M. tuberculosis to zwitterionic β-lactam antibiotics was substantially enhanced by MspA, decreasing the minimal inhibitory concentration up to 16-fold. Furthermore, M. tuberculosis became significantly more susceptible to isoniazid, ethambutol and streptomycin. Fluorescence with the nucleic acid binding dye SYTO 9 was 10-fold increased upon expression of mspA. These results indicated that MspA not only enhanced the efficiency of the porin pathway, but also that of pathways mediating access to large and/or hydrophobic agents. This study provides the first experimental evidence that porins are important for drug susceptibility of M. tuberculosis.

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Wang, Chun Fang, Hua Rui Qi, Xiu Yun Jiang, Hong Xia Ma, Ai Dong Qian e Chun Feng Wang. "Isolated Strains of Nontuberculous Mycobacterium Interfere with Immune Responses Associated with Mycobacterium Bovis BCG Vaccination". Advanced Materials Research 884-885 (gennaio 2014): 450–54. http://dx.doi.org/10.4028/www.scientific.net/amr.884-885.450.

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Prior exposure of a vaccine to certain species of environmental mycobacteria can prime the immune system against common mycobacterial antigens, which can in turn reduce the subsequent efficacy of live attenuated mycobacterial vaccines (such as Mycobacterium bovis BCG), in both human and livestock vaccination programs. In this study, five strains of nontubeculous mycobacterium, all isolated from lymphonodi mandibulares and lymphonodi mesenterici samples of swine and cattle, were investigated to determine their growth characteristics and effects on the immune system in murine models. Markedly, different effects on the immune system were observed. The different results may be linked to the inherent growth characteristics of the five strains, The implications of these findings for BCG vaccination protocols are discussed.

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Ghodbane, Ramzi, Felix Mba Medie, Hubert Lepidi, Claude Nappez e Michel Drancourt. "Long-term survival of tuberculosis complex mycobacteria in soil". Microbiology 160, n. 3 (1 marzo 2014): 496–501. http://dx.doi.org/10.1099/mic.0.073379-0.

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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 108 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 food that contained 16.7 % M. tuberculosis-contaminated soil. The three tested MTC species survived in soil for 12 months with a final inoculum of 2×103 c.f.u. g−1 for M. tuberculosis, 150 c.f.u. g−1 for M. bovis and 2×104 c.f.u. g−1 for M. canettii. In an experiment that included negative controls, all (5/5) mice inoculated with such M. tuberculosis and M. canettii developed 0.03–0.3 granulomas mm−2 in their lungs and spleen and grew mycobacteria; five mice that were inoculated with M. bovis from soil did not develop granulomas but grew mycobacteria. Furthermore, 0.2–0.4 granulomas mm−2 were observed in the lungs and spleen of 3/5 mice fed with M. tuberculosis-contaminated soil in the presence of two negative control mice. M. tuberculosis grew in the stomach, intestine, spleen and lung in 5/5 challenged mice, whereas the negative controls remained M. tuberculosis-free (P = 0.008, Fisher exact test). This study provides clear evidence that MTC mycobacteria survive in soil, and that M. tuberculosis remains virulent while in the soil, outside its hosts, for extended periods of time.

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Thoen, Charles O., William J. Quinn, Lyle D. Miller, Larry L. Stackhouse, Bradford F. Newcomb e James M. Ferrell. "Mycobacterium Bovis Infection in North American Elk (Cervus Elaphus)". Journal of Veterinary Diagnostic Investigation 4, n. 4 (ottobre 1992): 423–27. http://dx.doi.org/10.1177/104063879200400410.

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A naturally occurring outbreak of Mycobacterium bovid infection in captive wild elk (wapiti) in Montana was confirmed by mycobacteriologic examination. Twenty-eight of 143 elk responded to M. bovis purified protein derivative (PPD) tuberculin injected intradermally in the cervical region (SCT). The results of comparative cervical tuberculin skin tests conducted within 9 days of SCT revealed greater responses to M. bovis PPD tuberculin than to M. avium PPD tuberculin in 23 of 28 elk responding. At necropsy, several grossly visible tuberculous lesions were observed in the parenchyma of the lung, thoracic lymph nodes, and submandibular lymph nodes. Microscopic examination of appropriately stained tissue sections revealed the presence of granulomatous lesions containing acid-fast bacilli. An enzyme-linked immunosorbent assay (ELISA) was developed using a sarkosyl extract of M. bovis (antigen) and peroxidase-labeled protein G (conjugate); reactions were detected in the sera of 8 of 9 elk responding to M. bovis PPD tuberculin. Lymphocyte blastogenic assay responses were detected using M. bovis antigens in 7 of 9 elk positive on skin tests using M. bovis PPD.

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Lee, Jinhee, Keumhwa Choi, Michael R. Olin, Sang-Nae Cho e Thomas W. Molitor. "γδ T Cells in Immunity Induced by Mycobacterium bovis Bacillus Calmette-Guérin Vaccination". Infection and Immunity 72, n. 3 (marzo 2004): 1504–11. http://dx.doi.org/10.1128/iai.72.3.1504-1511.2004.

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ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination is efficacious for newborns or adults with no previous exposure to environmental mycobacteria. To determine the relative contribution and the nature of γδ T-cell receptor-positive T cells in newborns, compared to CD4+ T cells, in immunity induced by M. bovis BCG vaccination, 4-week-old specific-pathogen-free pigs were vaccinated with M. bovis BCG and monitored by following the γδ T-cell immune responses. A flow cytometry-based proliferation assay and intracellular staining for gamma interferon (IFN-γ) were used to examine γδ T-cell responses. Pigs were found to mount Th1-like responses to M. bovis BCG vaccination as determined by immunoproliferation and IFN-γ production. The γδ T-cell lymphoproliferation and IFN-γ production to stimulation with mycobacterial antigens were significantly enhanced by M. bovis BCG vaccination. The relative number of proliferating γδ T cells after stimulating peripheral blood mononuclear cells with Mycobacterium tuberculosis H37Rv culture filtrate protein was higher than that of CD4+ T cells at an early time point after M. bovis BCG vaccination, but CD4+ T cells were found to be more abundant at a later time point. Although the γδ T-cell responses were dependent on the presence of CD4+ T cells for the cytokine interleukin-2, the enhanced γδ T cells were due to the intrinsic changes of γδ T cells caused by M. bovis BCG vaccination rather than being due solely to help from CD4+ T cells. Our study shows that γδ T cells from pigs at early ages are functionally enhanced by M. bovis BCG vaccination and suggests an important role for this T-cell subset in acquired immunity conferred by M. bovis BCG vaccination.

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Skinner, Margot A., D. Neil Wedlock, Geoffrey W. de Lisle, Michèle M. Cooke, Ricardo E. Tascon, Jose C. Ferraz, Douglas B. Lowrie, H. Martin Vordermeier, R. Glyn Hewinson e Bryce M. Buddle. "The Order of Prime-Boost Vaccination of Neonatal Calves with Mycobacterium bovis BCG and a DNA Vaccine Encoding Mycobacterial Proteins Hsp65, Hsp70, and Apa Is Not Critical for Enhancing Protection against Bovine Tuberculosis". Infection and Immunity 73, n. 7 (luglio 2005): 4441–44. http://dx.doi.org/10.1128/iai.73.7.4441-4444.2005.

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Abstract (sommario):

ABSTRACT Priming neonatal calves at birth with a Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine and boosting with a DNA vaccine consisting of plasmids encoding mycobacterial antigens Hsp65, Hsp70, and Apa or the reverse prime-boost sequence induced similar levels of protection against experimental challenge with Mycobacterium bovis. When M. bovis was isolated from a thoracic lymph node following challenge, the two groups of calves given the prime-boost regimen had significantly lower numbers of M. bovis isolates than those vaccinated with BCG alone. These observations suggest that the exact sequence of administration of a prime-boost vaccination regimen in a neonatal animal model is not critical to the development of immunity.

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22

Nau, Gerard J., Lucy Liaw, Geoffrey L. Chupp, Jeffrey S. Berman, Brigid L. M. Hogan e Richard A. Young. "Attenuated Host Resistance againstMycobacterium bovis BCG Infection in Mice Lacking Osteopontin". Infection and Immunity 67, n. 8 (1 agosto 1999): 4223–30. http://dx.doi.org/10.1128/iai.67.8.4223-4230.1999.

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ABSTRACT Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial load. The ability of osteopontin to facilitate the clearance of mycobacteria was most pronounced early after infection and appeared to be independent of known mediators of resistance to infection by mycobacteria: antigen-specific T-cell immunity, gamma interferon production, and nitric oxide production. BCG grew more rapidly in macrophages derived from OPN-null mice than in those from wild-type mice, demonstrating that the null phenotype was due to an intrinsic macrophage defect. These results indicate that osteopontin augments the host response against a mycobacterial infection and that it acts independently from other antimycobacterial resistance mechanisms.

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23

Krajewska, Monika, Michał Załuski, Anna Zabost, Blanka Orłowska, Ewa Augustynowicz-Kopeć, Krzysztof Anusz, Marek Lipiec, Marcin Weiner e Krzysztof Szulowski. "Tuberculosis in Antelopes in a Zoo in Poland – Problem of Public Health". Polish Journal of Microbiology 64, n. 4 (31 dicembre 2015): 395–97. http://dx.doi.org/10.5604/17331331.1185242.

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Abstract (sommario):

Bovine tuberculosis is an infectious disease that occurs in many species of both domestic and wild animals, as well as those held in captivity. The etiological factor is the acid resistant bacillus (Mycobacterium bovis or Mycobacterium caprae), which is characterized by the major pathogenicity among mycobacteria belonging to the Mycobacterium tuberculosis complex. The material from 8 antelopes from the zoo, suspected for tuberculosis were examined, and M. bovis strains were isolated from 6 of them. The spoligotyping method showing spoligo pattern 676763777777600. In Poland, this spoligotype has not been observed so far.

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24

Platonova, Ya B., V. A. Kirillova, A. N. Volov e S. V. Savilov. "Synthesis and antituberculosis activity of new 5-alkynyl derivatives of 2-thiouridine: application of new scaffold". Журнал органической химии 59, n. 12 (15 dicembre 2023): 1598–607. http://dx.doi.org/10.31857/s0514749223120042.

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Abstract (sommario):

We herein describe new potent inhibitors of mycobacteria based on 5-substituted 2-thiouridine derivatives. A series of new 5-alkynyl-substituted 2-thiouridine derivatives were synthesized via palladium-catalysed Sonogashira cross-coupling reaction of 5-iodo-2-thiopyrimidine base with terminal acetylenes with good yields in DMF at room temperature. It was found that sulfur atom in C2 position of pyrimidine ring had no impact on yields of target compounds. All obtained compounds were evaluated for their antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis at concentrations of 0.1-100 µg/ml using MABA test. Synthesized nucleosides showed high antimycobacterial activity against Mycobacterium bovis and Mycobacteri um tuberculosis. The obtained MIC50 values of 2-thionucleosides 14, 15 and 16 (0.28-0.75 µg/ml) significantly exceed characteristics of reference drug rifampicin, D-cycloserine and isoniazid, which gives prerequisites for further more detailed studies.

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25

Guallar-Garrido, Sandra, Víctor Campo-Pérez, Alejandro Sánchez-Chardi, Marina Luquin e Esther Julián. "Each Mycobacterium Requires a Specific Culture Medium Composition for Triggering an Optimized Immunomodulatory and Antitumoral Effect". Microorganisms 8, n. 5 (14 maggio 2020): 734. http://dx.doi.org/10.3390/microorganisms8050734.

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Abstract (sommario):

Mycobacterium bovis bacillus Calmette-Guérin (BCG) remains the first treatment option for non-muscle-invasive bladder cancer (BC) patients. In research laboratories, M. bovis BCG is mainly grown in commercially available media supplemented with animal-derived agents that favor its growth, while biomass production for patient treatment is performed in Sauton medium which lacks animal-derived components. However, there is not a standardized formulation of Sauton medium, which could affect mycobacterial characteristics. Here, the impact of culture composition on the immunomodulatory and antitumor capacity of M. bovis BCG and Mycolicibacterium brumae, recently described as efficacious for BC treatment, has been addressed. Both mycobacteria grown in Middlebrook and different Sauton formulations, differing in the source of nitrogen and amount of carbon source, were studied. Our results indicate the relevance of culture medium composition on the antitumor effect triggered by mycobacteria, indicating that the most productive culture medium is not necessarily the formulation that provides the most favorable immunomodulatory profile and the highest capacity to inhibit BC cell growth. Strikingly, each mycobacterial species requires a specific culture medium composition to provide the best profile as an immunotherapeutic agent for BC treatment. Our results highlight the relevance of meticulousness in mycobacteria production, providing insight into the application of these bacteria in BC research.

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26

Uygur Külcü, Nihan, Feray Güven, Burçin Nalbantoğlu, Erdem Yılmaz, Engin Deniz, Ensar Yekeler e Aysu Say. "Mycobacterium Bovis Meningitis: Case Report". Journal of Pediatric Infection 6, n. 2 (14 giugno 2012): 59–63. http://dx.doi.org/10.5152/ced.2012.14.

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27

Fulton, Scott A., Scott M. Reba, Rish K. Pai, Meghan Pennini, Martha Torres, Clifford V. Harding e W. Henry Boom. "Inhibition of Major Histocompatibility Complex II Expression and Antigen Processing in Murine Alveolar Macrophages by Mycobacterium bovis BCG and the 19-Kilodalton Mycobacterial Lipoprotein". Infection and Immunity 72, n. 4 (aprile 2004): 2101–10. http://dx.doi.org/10.1128/iai.72.4.2101-2110.2004.

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Abstract (sommario):

ABSTRACT Alveolar macrophages constitute a primary defense against Mycobacterium tuberculosis, but they are unable to control M. tuberculosis without acquired T-cell immunity. This study determined the antigen-presenting cell function of murine alveolar macrophages and the ability of the model mycobacterium, Mycobacterium bovis BCG, to modulate it. The majority (80 to 85%) of alveolar macrophages expressed both CD80 (B7.1) and CD11c, and 20 to 30% coexpressed major histocompatibility complex II (MHC-II). Gamma interferon (IFN-γ) enhanced MHC-II but not B7.1 expression. Naive or IFN-γ-treated alveolar macrophages did not express CD86 (B7.2), CD11b, Mac-3, CD40, or F4/80. M. bovis BCG and the 19-kDa mycobacterial lipoprotein inhibited IFN-γ-regulated MHC-II expression on alveolar macrophages, and inhibition was dependent on Toll-like receptor 2. The inhibition of MHC-II expression by the 19-kDa lipoprotein was associated with decreased presentation of soluble antigen to T cells. Thus, susceptibility to tuberculosis may result from the ability of mycobacteria to interfere with MHC-II expression and antigen presentation by alveolar macrophages.

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28

Norton, Robert E., Richard Lumb e David R. Shaw. "Mycobacterium bovis meningitis". Medical Journal of Australia 162, n. 5 (marzo 1995): 276–77. http://dx.doi.org/10.5694/j.1326-5377.1995.tb139890.x.

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29

Nandavaram, Sravanthi, Abdullah Al Twal, Helen Jacoby e Robert Lenox. "Mycobacterium bovis Aneurysm". Infectious Diseases in Clinical Practice 24, n. 6 (novembre 2016): e69-e70. http://dx.doi.org/10.1097/ipc.0000000000000438.

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30

Unsworth, J. D., e A. Bonington. "Mycobacterium bovis tenosynovitis". Case Reports 2013, jun13 1 (13 giugno 2013): bcr2013009257. http://dx.doi.org/10.1136/bcr-2013-009257.

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31

Panesar, Jaswinder, Kevin Higgins, Vito Forte e Upton Allen. "Revisiting Mycobacterium bovis". Journal of Otolaryngology 31, n. 01 (2002): 58. http://dx.doi.org/10.2310/7070.2002.19248.

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32

Holdiness, M. R. "Mycobacterium bovis infection". Archives of Internal Medicine 145, n. 10 (1 ottobre 1985): 1930b—1930. http://dx.doi.org/10.1001/archinte.145.10.1930b.

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33

Holdiness, Mack R. "Mycobacterium bovis Infection". Archives of Internal Medicine 145, n. 10 (1 ottobre 1985): 1930. http://dx.doi.org/10.1001/archinte.1985.00360100204047.

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34

Moriconi, Patricia Rossi, Cássia Yumi Ikuta, Fábio Gregori, Gisele de Oliveira, Sheila de Oliveira, Paloma De Oliveira Tonietti, José Soares Ferreira Neto, Fernando Ferreira, Adriana Cortez e Evelise Oliveira Telles. "Mycobacteria in Minas cheese commercialized in open fairs in São Paulo, Brazil". Brazilian Journal of Veterinary Research and Animal Science 55, n. 4 (26 dicembre 2018): e146525. http://dx.doi.org/10.11606/issn.1678-4456.bjvras.2018.146525.

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Abstract (sommario):

Mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that affects dairy herds throughout the Brazilian territory, constituting a neglected zoonosis transmitted by raw milk and its derivatives. In this study, we evaluated the presence of M. bovis and other mycobacteria in Minas cheese obtained from open fairs in the city of São Paulo between 2012 and 2013. Samples (n = 133) were decontaminated using hexa-cetylpyridinium chloride and seeded on Stonebrink–Leslie medium. The isolates were submitted to molecular identification by TB Multiplex PCR targeting the 16S rRNA gene and amplicon nucleotide sequencing. From 16 cheese samples (12%), we obtained 26 putative colonies of Mycobacterium spp., none of which belonged to any of the Mycobacterium tuberculosis, Mycobacterium avium, or Mycobacterium intracellulare complexes. Phylogenetic analysis showed that sample sequences were grouped in a clade that includes only non-tuberculous mycobacteria with proximity to sequences obtained from Mycobacterium novocastrense (3 sequences), Mycobacterium holsaticum (1 sequence), andMycobacterium elephantis (2 sequences). Although no epidemiological evidence was found regarding the importance of oral transmission of mycobacteria in healthy people, their importance in the immunosuppressed population remains uncertain.

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35

Rochard, Vincent, Thierry Cochard, Stéphanie Crapart, Vincent Delafont, Jean-Louis Moyen, Yann Héchard e Franck Biet. "Presence of Non-Tuberculous Mycobacteria Including Mycobacterium avium subsp. paratuberculosis Associated with Environmental Amoebae". Animals 13, n. 11 (27 maggio 2023): 1781. http://dx.doi.org/10.3390/ani13111781.

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One of the obstacles to eradicating paratuberculosis or Johne’s Disease (JD) seems to be the persistence of Mycobacterium avium subsp. paratuberculosis (Map) in the environment due to its ability to survive alone or vectorized. It has been shown that Map is widely distributed in soils and water. Previously, we isolated amoebae associated with Map strains in the environment of bovines from an infected herd. This work aims to verify our working hypothesis, which suggests that amoebae may play a role in the transmission of JD. In this study, we sampled water in the vicinity of herds infected with Map or Mycobacterium bovis (M. bovis) and searched for amoebae and mycobacteria. Live amoebae were recovered from all samples. Among these amoebae, four isolates associated with the presence of mycobacteria were identified and characterized. Map and other mycobacterial species were detected by qPCR and, in some cases, by culture. This study suggests that amoebae and Map may be found in the same environment and might represent a risk of exposure of animals to pathogenic mycobacteria. These data open up new perspectives on the control measures to be put in place to prevent contamination by Map.

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36

Nicolle, Delphine, Cécile Fremond, Xavier Pichon, André Bouchot, Isabelle Maillet, Bernhard Ryffel e Valerie J. F. Quesniaux. "Long-Term Control of Mycobacterium bovis BCG Infection in the Absence of Toll-Like Receptors (TLRs): Investigation of TLR2-, TLR6-, or TLR2-TLR4-Deficient Mice". Infection and Immunity 72, n. 12 (dicembre 2004): 6994–7004. http://dx.doi.org/10.1128/iai.72.12.6994-7004.2004.

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Abstract (sommario):

ABSTRACT Live mycobacteria have been reported to signal through both Toll-like receptor 2 (TLR2) and TLR4 in vitro. Here, we investigated the role of TLR2 in the long-term control of the infection by the attenuated Mycobacterium, Mycobacterium bovis BCG, in vivo. We sought to determine whether the reported initial defect of bacterial control (K. A. Heldwein et al., J. Leukoc. Biol. 74:277-286, 2003) resolved in the chronic phase of BCG infection. Here we show that TLR2-deficient mice survived a 6-month infection period with M. bovis BCG and were able to control bacterial growth. Granuloma formation, T-cell and macrophage recruitment, and activation were normal. Furthermore, the TLR2 coreceptor, TLR6, is also not required since TLR6-deficient mice were able to control chronic BCG infection. Finally, TLR2-TLR4-deficient mice infected with BCG survived the 8-month observation period. Interestingly, the adaptive response of TLR2- and/or TLR4-deficient mice seemed essentially normal on day 14 or 56 after infection, since T cells responded normally to soluble BCG antigens. In conclusion, our data demonstrate that TLR2, TLR4, or TLR6 are redundant for the control of M. bovis BCG mycobacterial infection.

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37

Chilima, Benson Z., Ian M. Clark, Sian Floyd, Paul E. M. Fine e Penny R. Hirsch. "Distribution of Environmental Mycobacteria in Karonga District, Northern Malawi". Applied and Environmental Microbiology 72, n. 4 (aprile 2006): 2343–50. http://dx.doi.org/10.1128/aem.72.4.2343-2350.2006.

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Abstract (sommario):

ABSTRACT The genus Mycobacterium includes many species that are commonly found in the environment (in soil and water or associated with plants and animals), as well as species that are responsible for two major human diseases, tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae). The distribution of environmental mycobacteria was investigated in the context of a long-term study of leprosy, tuberculosis, Mycobacterium bovis BCG vaccination, and the responses of individuals to various mycobacterial antigens in Karonga District, northern Malawi, where epidemiological studies had indicated previously that people may be exposed to different mycobacterial species in the northern and southern parts of the district. A total of 148 soil samples and 24 water samples were collected from various locations and examined to determine the presence of mycobacteria. The detection method involved semiselective culturing and acid-fast staining, following decontamination of samples to enrich mycobacteria and reduce the numbers of other microorganisms, or PCR with primers specific for the mycobacterial 16S rRNA gene, using DNA extracted directly from soil and water samples. Mycobacteria were detected in the majority of the samples, and subsequent sequence analysis of PCR products amplified directly from soil DNA indicated that most of the products were related to known environmental mycobacteria. For both methods the rates of recovery were consistently higher for dry season samples than for wet season samples. All isolates cultured from soil appeared to be strains of Mycobacterium fortuitum. This study revealed a complex pattern for the environmental mycobacterial flora but identified no clear differences between the northern and southern parts of Karonga District.

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38

Beatty, Wandy L., e David G. Russell. "Identification of Mycobacterial Surface Proteins Released into Subcellular Compartments of Infected Macrophages". Infection and Immunity 68, n. 12 (1 dicembre 2000): 6997–7002. http://dx.doi.org/10.1128/iai.68.12.6997-7002.2000.

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Abstract (sommario):

ABSTRACT Considerable effort has focused on the identification of proteins secreted from Mycobacterium spp. that contribute to the development of protective immunity. Little is known, however, about the release of mycobacterial proteins from the bacterial phagosome and the potential role of these molecules in chronically infected macrophages. In the present study, the release of mycobacterial surface proteins from the bacterial phagosome into subcellular compartments of infected macrophages was analyzed. Mycobacterium bovis BCG was surface labeled with fluorescein-tagged succinimidyl ester, an amine-reactive probe. The fluorescein tag was then used as a marker for the release of bacterial proteins in infected macrophages. Fractionation studies revealed bacterial proteins within subcellular compartments distinct from mycobacteria and mycobacterial phagosomes. To identify these proteins, subcellular fractions free of bacteria were probed with mycobacterium-specific antibodies. The fibronectin attachment protein and proteins of the antigen 85-kDa complex were identified among the mycobacterial proteins released from the bacterial phagosome.

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39

Li, Xiaohui, Liu Chen, Jingjing Liao, Jiechen Hui, Weihui Li e Zheng-Guo He. "A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress". Journal of Biological Chemistry 295, n. 50 (8 ottobre 2020): 17083–99. http://dx.doi.org/10.1074/jbc.ra120.013017.

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Abstract (sommario):

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

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40

Fine, Amanda E., Daniel J. O'Brien, Scott R. Winterstein e John B. Kaneene. "An Effort to Isolate Mycobacterium bovis from Environmental Substrates during Investigations of Bovine Tuberculosis Transmission Sites (Cattle Farms and Wildlife Areas) in Michigan, USA". ISRN Veterinary Science 2011 (22 settembre 2011): 1–11. http://dx.doi.org/10.5402/2011/787181.

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Abstract (sommario):

Deer movements on cattle farms, wildlife feeding, and livestock management practices in Michigan are thought to create opportunities for indirect transmission of Mycobacterium bovis via environmental substrates. To confirm the presence of viable M. bovis in the environment, substrates were collected from 13 farms with culture-confirmed M. bovis in cattle and 5 sites with high prevalence of M. bovis in free-ranging deer. None of the samples processed for mycobacterial culture were positive for M. bovis. Agent, host, and landscape-level factors decrease the probability of detecting M. bovis in the environment using conventional mycobacterial culture. Molecular techniques that increase the probability of M. bovis detection in environmental substrates should be applied to known sites of M. bovis transmission in Michigan. In the interim, epidemiological investigations informed by experimental studies will be most effective in characterizing M. bovis persistence in the environment and its role in the indirect interspecies transmission of M. bovis.

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41

Fujita, Yukiko, Takashi Naka, Michael R. McNeil e Ikuya Yano. "Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry". Microbiology 151, n. 10 (1 ottobre 2005): 3403–16. http://dx.doi.org/10.1099/mic.0.28158-0.

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Abstract (sommario):

Cord factor (trehalose 6,6′-dimycolate, TDM) is an unique glycolipid with a trehalose and two molecules of mycolic acids in the mycobacterial cell envelope. Since TDM consists of two molecules of very long branched-chain 3-hydroxy fatty acids, the molecular mass ranges widely and in a complex manner. To characterize the molecular structure of TDM precisely and simply, an attempt was made to determine the mycolic acid subclasses of TDM and the molecular species composition of intact TDM by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the first time. The results showed that less than 1 μg mycolic acid methyl ester of TDM from nine representative species of mycobacteria and TDM from the same species was sufficient to obtain well-resolved mass spectra composed of pseudomolecular ions [M+Na]+. Although the mass ion distribution was extremely diverse, the molecular species of each TDM was identified clearly by constructing a molecular ion matrix consisting of the combination of two molecules of mycolic acids. The results showed a marked difference in the molecular structure of TDM among mycobacterial species and subspecies. TDM from Mycobacterium tuberculosis (H37Rv and Aoyama B) showed a distinctive mass pattern and consisted of over 60 molecular ions with α-, methoxy- and ketomycolate. TDM from Mycobacterium bovis BCG Tokyo 172 similarly showed over 35 molecular ions, but that from M. bovis BCG Connaught showed simpler molecular ion clusters consisting of less than 35 molecular species due to a complete lack of methoxymycolate. Mass ions due to TDM from M. bovis BCG Connaught and Mycobacterium kansasii showed a biphasic distribution, but the two major peaks of TDM from M. kansasii were shifted up two or three carbon units higher compared with M. bovis BCG Connaught. Within the rapid grower group, in TDM consisting of α-, keto- and wax ester mycolate from Mycobacterium phlei and Mycobacterium flavescens, the mass ion distribution due to polar mycolates was shifted lower than that from the Mycobacterium avium–intracellulare group. Since the physico-chemical properties and antigenic structure of mycolic acid of TDM affect the host immune responses profoundly, the molecular characterization of TDM by MALDI-TOF mass analysis may give very useful information on the relationship of glycolipid structure to its biological activity.

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42

Marassi, Carla D., Flávia C. S. de Oliveira, Sonia R. Pinheiro, Sergio S. Azevedo, Francisco R. M. Soto, Walter Oelemann, Walter Lilenbaum e Silvio A. Vasconcellos. "Evaluation of a MPB70-ELISA to differentiate Mycobacterium bovis from M. avium-sensitized swine". Pesquisa Veterinária Brasileira 34, n. 11 (novembre 2014): 1069–72. http://dx.doi.org/10.1590/s0100-736x2014001100005.

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Abstract (sommario):

Swine are susceptible to different mycobacteria species, being Mycobacterium bovis an agent of tuberculosis, with most significant zoonotic risks, while M. avium determines a granulomatous lymphadenitis with low zoonotic risk. Currently performed intradermal tests present some important limitations, such as the lack of ability to detect anergic animals or to differentiate among mycobacterial species. In order to improve the TB diagnosis, serological assays have been developed, with encouraging results. The purpose of this study was to evaluate the performance of a MPB70-ELISA in 82 piglets divided into four groups: sensitized by inactivated M. bovis, M. avium, inoculated with oil adjuvant, or with saline solution. The test was able to discriminate between an animal sensitized by M. bovis and animals of the three other groups, including M. avium-sensitized animals; for this reason, we suggest that MPB70-ELISA could be used as a complementary tool for discriminating the agent of the mycobacteriosis, and therefore to diagnose tuberculosis in a swine herd.

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43

ÖZTÜRK, Cihadiye Elif, İdris ŞAHİN, Şükrü ÖKSÜZ, Nida KILIÇ, Özge KILINÇEL, Leyla AYDIN, Dursun ATİK e Emine AFŞİN. "Investigation of Mycobacterium bovis subsp. bovis Among the Strains of Mycobacterium tuberculosis Complex Isolated in Düzce Province, Turkey". Mikrobiyoloji Bulteni 50, n. 3 (29 luglio 2016): 392–400. http://dx.doi.org/10.5578/mb.27784.

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44

Paarwater, Brandon A., Jomien M. Mouton, Samantha L. Sampson, Stephanus T. Malherbe, Jane A. Shaw, Gerhard Walzl, Leigh A. Kotze e Nelita du Plessis. "Inhaled particulate matter affects immune responsiveness of human lung phagocytes to mycobacteria". American Journal of Physiology-Lung Cellular and Molecular Physiology 321, n. 3 (1 settembre 2021): L566—L575. http://dx.doi.org/10.1152/ajplung.00014.2021.

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Abstract (sommario):

The influence of smoke-derived or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and can lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune-mediator responses of human bronchoalveolar lavage cells (BALCs) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALCs containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL)-10 production. PM-loaded BALCs retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis ( M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM-loaded BALCs. However, immune responsiveness, such as the production of IL-6 ( P = 0.015) and tumor necrosis factor-α (TNF)-α ( P = 0.0172) immediately post M. bovis BCG infection, were dramatically lower in black BALCs loaded with PM versus clear non-PM-loaded BALCs. By 24 h post infection, differential immune responses to M. bovis BCG between black versus clear BALC waned, and instead, production of IL-6 ( P = 0.03) and IL-1α ( P = 0.04) by black BALCs was lower versus clear BALCs following M.tb ΔleuDΔpanCD infection. Considering that TNF-α and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALCs loaded with inhaled PM, display lower levels of antimycobacterial mediators and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.

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45

Arain, T. M., A. E. Resconi, D. C. Singh e C. K. Stover. "Reporter gene technology to assess activity of antimycobacterial agents in macrophages." Antimicrobial Agents and Chemotherapy 40, n. 6 (giugno 1996): 1542–44. http://dx.doi.org/10.1128/aac.40.6.1542.

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Reporter strains of Mycobacterium tuberculosis and Mycobacterium bovis BCG endogenously expressing firefly luciferase were used in bioluminescence assays to evaluate the activities of isoniazid and rifampin against mycobacteria sequestered in human macrophages. This methodology allowed the efficacy of antibiotics against intracellular mycobacteria to be assessed without the labor-intensive procedures and protracted incubation requirements associated with conventional CFU determinations.

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46

Silva, Pedro E. A., Fabiana Bigi, Marı́a de la Paz Santangelo, Maria Isabel Romano, Carlos Martı́n, Angel Cataldi e José A. Aı́nsa. "Characterization of P55, a Multidrug Efflux Pump inMycobacterium bovis and Mycobacterium tuberculosis". Antimicrobial Agents and Chemotherapy 45, n. 3 (1 marzo 2001): 800–804. http://dx.doi.org/10.1128/aac.45.3.800-804.2001.

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ABSTRACT The Mycobacterium bovis P55 gene, located downstream from the gene that encodes the immunogenic lipoprotein P27, has been characterized. The gene was identical to the open reading frame of the Rv1410c gene in the genome of Mycobacterium tuberculosisH37Rv, annotated as a probable drug efflux protein. Genes similar toP55 were present in all species of the M. tuberculosis complex and other mycobacteria such asMycobacterium leprae and Mycobacterium avium. By Western blotting, P55 was located in the membrane fraction ofM. bovis. When transformed into Mycobacterium smegmatis after cloning, P55 conferred aminoglycoside and tetracycline resistance. The levels of resistance to streptomycin and tetracycline conferred by P55 were decreased in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the pump inhibitors verapamil and reserpine. M. smegmatiscells expressing the plasmid-encoded P55 accumulated less tetracycline than the control cells. We conclude that P55 is a membrane protein implicated in aminoglycoside and tetracycline efflux in mycobacteria.

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47

Young, Jamie S., Eamonn Gormley e Elizabeth M. H. Wellington. "Molecular Detection of Mycobacterium bovis and Mycobacterium bovis BCG (Pasteur) in Soil". Applied and Environmental Microbiology 71, n. 4 (aprile 2005): 1946–52. http://dx.doi.org/10.1128/aem.71.4.1946-1952.2005.

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ABSTRACT PCR primers specific for the Mycobacterium tuberculosis complex were used to detect the presence of Mycobacterium bovis BCG (Pasteur) in soil microcosms and Mycobacterium bovis in environmental samples taken from a farm in Ireland with a history of bovine tuberculosis. M. bovis genes were detected in soil at 4 and 21 months after possible contamination. Gene levels were found in the range of 1 × 103 to 3.6 × 103 gene copies g of soil−1, depending on the sampling area. Areas around badger setts had the highest levels of detectable genes and were shown to have the highest levels of gene persistence. M. bovis-specific 16S rRNA sequences were detected, providing evidence of the presence of viable cells in Irish soils. Studies of DNA turnover in soil microcosms proved that dead cells of M. bovis BCG did not persist beyond 10 days. Further microcosm experiments revealed that M. bovis BCG survival was optimal at 37°C with moist soil (−20 kPa; 30% [vol/wt]). This study provides clear evidence that M. bovis can persist in the farm environment outside of its hosts and that climatic factors influence survival rates.

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48

Kadival, G. V., S. D. Chaparas e D. Hussong. "Characterization of serologic and cell-mediated reactivity of a 38-kDa antigen isolated from Mycobacterium tuberculosis." Journal of Immunology 139, n. 7 (1 ottobre 1987): 2447–51. http://dx.doi.org/10.4049/jimmunol.139.7.2447.

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Abstract An antigen of Mycobacterium tuberculosis with an m.w. of 38,000 has been isolated by affinity chromatography using a monoclonal antibody. This antibody bound only to an antigen found in M. tuberculosis and Mycobacterium bovis BCG. The specificity of the antigen was tested in a vertical study by immunodetection on western blots reacted with hyperimmune sera against M. tuberculosis, M. bovis, and 10 other Mycobacterium species. The antigen was detected only by antisera to M. tuberculosis and M. bovis. Specificity in cell-mediated immunity was tested by skin tests in guinea pigs sensitized with M. tuberculosis, Mycobacterium intracellulare, and Mycobacterium kansasii and by lymphocyte proliferation tests. The 38-kDa antigen induced positive skin test reactions regardless of the Mycobacterium species used to sensitize the animal. The ability of the 38-kDa antigen to sensitize for cell-mediated immunity was tested by injecting mice with the 38-kDa antigen and challenging their lymphocytes in vitro with various mycobacterial antigens. Lymphocyte proliferation was observed in the presence of 38-kDa antigen, M. tuberculosis sonicate antigen, and tuberculin purified protein derivative and to M. kansasii and M. intracellulare. The 38-kDa antigen may contain a specific epitope detected by serology, but also contains epitopes that are cross-reactive for cellular immunity.

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49

Tran, Huyen Thi, Julia Solnier, Eva-Maria Pferschy-Wenzig, Olaf Kunert, Liam Martin, Sanjib Bhakta, Loi Huynh, Tri Minh Le, Rudolf Bauer e Franz Bucar. "Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Sphaeranthus africanus Against Mycobacteria". Antibiotics 9, n. 7 (8 luglio 2020): 390. http://dx.doi.org/10.3390/antibiotics9070390.

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Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc2 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds 1 and 6 to accumulate ethidium bromide (EtBr) in M. smegmatis and M. aurum, a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds 1 and 6 were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against M. smegmatis. Carvotacetones 1 and 6 had potent antibacterial effects on M. aurum and M. bovis BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against M. smegmatis. Compound 1 appeared as the most efficient agent for impairing the efflux mechanism in M. smegmatis. Both compounds 1 and 6 were highly effective against M. aurum and M. bovis BCG. In particular, compound 1 was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.

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50

Lumb, Richard. "The rational use of nucleic acid amplification testing for the Mycobacterium tuberculosis complex". Microbiology Australia 25, n. 4 (2004): 28. http://dx.doi.org/10.1071/ma04428.

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Abstract (sommario):

On the basis of clinical significance, Mycobacterium tuberculosis is the most important member of the genus Mycobacterium. It is closely related genetically to Mycobacterium bovis, M. africanum, Mycobacterium microti, Mycobacterium bovis BCG (the bacillus of Calmette-Guerin) and the recently described Mycobacterium tuberculosis subspecies Canetti. Together they are termed the Mycobacterium tuberculosis complex (MTBC).

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