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

The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo Summary 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Microbiology Wiley

Loading next page...
 
/lp/wiley/the-principal-sigma-factor-siga-mediates-enhanced-growth-of-6NTFK3fzG4
Publisher
Wiley
Copyright
Copyright © 2004 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0950-382X
eISSN
1365-2958
DOI
10.1111/j.1365-2958.2003.03922.x
Publisher site
See Article on Publisher Site

Abstract

Summary 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.

Journal

Molecular MicrobiologyWiley

Published: Mar 1, 2004

References

  • sigA is an essential gene in Mycobacterium smegmatis
    Gomez, Gomez; Doukhan, Doukhan; Nair, Nair; Smith, Smith
  • Identification and characterization of a stress‐responsive promoter in the macromolecular synthesis operon of Bacillus subtilis
    Liao, Liao; Wen, Wen; Wang, Wang; Chang, Chang
  • Differential expression of 10 sigma factor genes in Mycobacterium tuberculosis
    Manganelli, Manganelli; Dubnau, Dubnau; Tyagi, Tyagi; Kramer, Kramer; Smith, Smith
  • An essential role for phoP in Mycobacterium tuberculosis virulence
    Perez, Perez; Samper, Samper; Bordas, Bordas; Guilhot, Guilhot; Gicquel, Gicquel; Martin, Martin
  • The bundle‐forming pili of enteropathogenic Escherichia coli: transcriptional regulation by environmental signals
    Puente, Puente; Bieber, Bieber; Ramer, Ramer; Murray, Murray; Schoolnik, Schoolnik
  • The Bordetella pertussis sigma subunit of RNA polymerase confers enhanced expression of fha in Escherichia coli
    Steffen, Steffen; Goyard, Goyard; Ullmann, Ullmann

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off