Intracellular replication of attenuated Mycobacterium tuberculosis phoP mutant in the absence of host cell cytotoxicity |
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| Institution: | 1. Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Spain;2. Unit of Mycobacterial Genetics, Institut Pasteur, Paris, France;3. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Spain;4. CIBER Enfermedades Respiratorias, Spain;1. Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico;2. National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;3. Westat, Rockville, Maryland;4. Leidos Biomedical, Bethesda, Maryland;6. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;5. Instituto Nacional de Pediatría, Mexico City, Mexico;7. Hospital Central “Dr. Ignacio Morones Prieto,” San Luis Potosí, México;1. Departamento de Genética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social (IMSS), Monterrey, Nuevo León, México;2. Departamento de Biología, Unidad de Genética, Universidad Autónoma de Madrid (UAM), Madrid, Spain;3. Unidad de Genética, Unit, INIBIC, Complejo Hospitalario Universitario A Coruña, La Coruña, Spain;4. Servicios de Veterinaria de la Armada Española (FESCCR-Ministerio de Defensa), Ávila, Spain;3. Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523 and;4. Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan;1. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico;2. Departamento de Física, UNESP – Univ. Estadual Paulista, Av. 24A, 1515, Bela Vista, 13506-900 Rio Claro, SP, Brazil;3. Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apartado Postal J-48, Puebla 72570, Mexico;1. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India;2. Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India;1. Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apartado Postal J-48, Puebla 72570, Mexico;2. UNESP - Univ Estadual Paulista, Câmpus São João da Boa Vista, São João da Boa Vista, SP 13874-149, Brazil;3. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico;4. Departamento de Física, UNESP - Univ Estadual Paulista, Av. 24A, 1515, Bela Vista, 13506-900 Rio Claro, SP, Brazil;5. Abdus Salam International Center for Theoretical Physics, Strada Costiera 11, 34151 Trieste, Italy |
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| Abstract: | Intracellular pathogen Mycobacterium tuberculosis survives and replicates in macrophages but limited information is available on its replication into non-phagocytic cells. Here we study the role of the M. tuberculosis virulence gene phoP in the intracellular growth with rat and human lung fibroblasts. In contrast to macrophages, attenuated M. tuberculosis phoP mutant was able to multiply intracellularly in fibroblasts at the same level as the virulent M. tuberculosis. However, when M. tuberculosis virulence was studied using human foetal lung fibroblasts, MRC-5 cell line, the virulent strain caused a significant damage in cells compared with attenuated strains BCG and M. tuberculosis phoP mutant. We analysed the effect of cytoskeleton inhibitors in NRK-49F fibroblasts. M. tuberculosis invasion was not inhibited, suggesting that mycobacterial uptake was microtubule and microfilament independent. Our results suggest that PhoP in M. tuberculosis does not regulate intracellular replication in fibroblasts, contrary to what happens in macrophages. The ability of M. tuberculosis phoP mutant to replicate within non-phagocytic cells, such as fibroblasts, without causing damage, could be a potential advantage for a live attenuated vaccine against tuberculosis. |
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