The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo
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Data
2004
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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.
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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.