Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP
Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobac...
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| Veröffentlicht in: | PLoS pathogens 2008-02, Vol.4 (2), p.e33-e33 |
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| creator | Frigui, Wafa Bottai, Daria Majlessi, Laleh Monot, Marc Josselin, Emmanuelle Brodin, Priscille Garnier, Thierry Gicquel, Brigitte Martin, Carlos Leclerc, Claude Cole, Stewart T Brosch, Roland |
| description | Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobacterium bovis BCG (BCG) and Mycobacterium tuberculosis H37Ra (H37Ra), which both lost their virulence during in vitro serial passage. Whereas the attenuation of BCG is due mainly to loss of the ESAT-6 secretion system, ESX-1, the reason why H37Ra is attenuated remained unknown. However, here we show that a point mutation (S219L) in the predicted DNA binding region of the regulator PhoP is involved in the attenuation of H37Ra via a mechanism that impacts on the secretion of the major T cell antigen ESAT-6. Only H37Ra "knock-ins" that carried an integrated cosmid with the wild-type phoP gene from M. tuberculosis H37Rv showed changes in colony morphology, increased virulence, ESAT-6 secretion, and induction of specific T cell responses, whereas other H37Ra constructs did not. This finding established a link between the PhoP regulator and ESAT-6 secretion that opens exciting new perspectives for elucidating virulence regulation in M. tuberculosis. |
| doi_str_mv | 10.1371/journal.ppat.0040033 |
| format | Article |
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Frigui W, Bottai D, Majlessi L, Monot M, Josselin E, et al. (2008) Control of M. tuberculosis ESAT-6 Secretion and Specific T Cell Recognition by PhoP. 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| subjects | Animals Antigens, Bacterial Antigens, Bacterial - genetics Antigens, Bacterial - immunology Antigens, Bacterial - metabolism Bacterial Proteins Bacterial Proteins - genetics Bacterial Proteins - immunology Bacterial Proteins - metabolism Biochemistry, Molecular Biology Cells, Cultured Disease Models, Animal DNA Mutational Analysis Eubacteria Gene Expression Regulation Genes Infectious Diseases Life Sciences Lymphocyte Activation Macrophages Macrophages - microbiology Male Mice Mice, SCID Microbiology Molecular Biology Mutation Mycobacterium bovis Mycobacterium tuberculosis Mycobacterium tuberculosis - metabolism Mycobacterium tuberculosis - pathogenicity Oligonucleotide Array Sequence Analysis Spleen Spleen - cytology Spleen - immunology Studies T-Lymphocytes T-Lymphocytes - immunology Tuberculosis Virulence |
| title | Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP |
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