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Tipo do documento: Artigo
Título: The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo
Autor: Wu, Shiping
Howard, Susan T.
Lakey, David L.
Kipnis, Andre
Samten, Buka
Safi, Hassan
Gruppo, Veronica
Wizel, Benjamin
Shams, Homayoun
Basaraba, Randall J.
Orme, Ian M.
Barnes, Peter F.
Abstract: The ability of Mycobacterium tuberculosis to grow in macrophages is central to its pathogenicity. We found previously that the widespread 210 strain of M. tuberculosis grew more rapidly than other strains in human macrophages. Because principal sigma factors influence virulence in some bacteria, we analysed mRNA expression of the principal sigma factor, sigA , in M. tuberculosis isolates during growth in human macrophages. Isolates of the 210 strain had higher sigA mRNA levels and higher intracellular growth rates, compared with other clinical strains and the laboratory strain H37Rv. SigA was also upregulated in the 210 isolate TB294 during growth in macrophages, compared with growth in broth. In contrast, H37Rv sigA mRNA levels did not change under these conditions. Overexpression of sigA enhanced growth of recombinant M. tuberculosis in macrophages and in lungs of mice after aerosol infection, whereas recombinant strains expressing antisense transcripts to sigA showed decreased growth in both models. In the presence of superoxide, sense sigA transformants showed greater resistance than vector controls, and the antisense sigA transformant did not grow. We conclude that M. tuberculosis sigA modulates the expression of genes that contribute to virulence, enhancing growth in human macrophages and during the early phases of pulmonary infection in vivo . This effect may be mediated in part by increased resistance to reactive oxygen intermediates.
País: Gra-bretanha
Unidade acadêmica: Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Citação: WU, Shiping et al. The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo. Molecular Microbiology, Oxford, v. 51, n. 6, p. 1551-1562, 2004.
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1111/j.1365-2958.2003.03922.x
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Identificador do documento: 10.1111/j.1365-2958.2003.03922.x
Data de publicação: 2004
Aparece nas coleções:IPTSP - Artigos publicados em periódicos

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