Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis


Parish, T; Smith, DA; Kendall, S; Casali, N; Bancroft, GJ; Stoker, NG; (2003) Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis. Infection and immunity, 71 (3). pp. 1134-40. ISSN 0019-9567 DOI: https://doi.org/10.1128/iai.71.3.1134-1140.2003

Full text not available from this repository. (Request a copy)

Abstract

Two-component regulatory signal transduction systems are widely distributed among bacteria and enable the organisms to make coordinated changes in gene expression in response to a variety of environmental stimuli. The genome sequence of Mycobacterium tuberculosis contains 11 complete two-component systems, four isolated homologous regulators, and three isolated homologous sensors. We have constructed defined mutations in six of these genes and measured virulence in a SCID mouse model. Mice infected with four of the mutants (deletions of devR, tcrXY, trcS, and kdpDE) died more rapidly than those infected with wild-type bacteria. The other two mutants (narL and Rv3220c) showed no change compared to the wild-type H37Rv strain. The most hypervirulent mutant (devRdelta) also grew more rapidly in the acute stage of infection in immunocompetent mice and in gamma interferon-activated macrophages. These results define a novel class of genes in this pathogen whose presence slows down its multiplication in vivo or increases its susceptibility to host killing mechanisms. Thus, M. tuberculosis actively maintains a balance between its own survival and that of the host.

Item Type: Article
Keywords: Animal, Gene Deletion, Macrophages/microbiology, Mice, Mice, Inbred DBA, Mice, SCID, Mycobacterium tuberculosis/genetics/metabolism/*pathogenicity, *Signal Transduction, Support, Non-U.S. Gov't, Virulence, Animal, Gene Deletion, Macrophages, microbiology, Mice, Mice, Inbred DBA, Mice, SCID, Mycobacterium tuberculosis, genetics, metabolism, pathogenicity, Signal Transduction, Support, Non-U.S. Gov't, Virulence
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: TB Centre
PubMed ID: 12595424
Web of Science ID: 181270900012
URI: http://researchonline.lshtm.ac.uk/id/eprint/16516

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
311Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item