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Infection and Immunity, August 2003, p. 4405-4413, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4405-4413.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent

Clare E. Blue and Tim. J. Mitchell*

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom

Received 20 December 2002/ Returned for modification 9 April 2003/ Accepted 8 May 2003

Bacterial two-component signal transduction systems (TCS) enable bacteria to respond to environmental changes and regulate a range of genes accordingly. They have a crucial role in regulating many cellular responses and have excellent potential as antibacterial-drug targets. We have constructed mutations in a TCS response regulator gene for two different strains of the human pathogen Streptococcus pneumoniae. These mutants have been analyzed in our murine model of infection. Data suggest that in a D39 background the response regulator gene is essential for virulence; an isogenic mutant is avirulent via intraperitoneal, intranasal, and intravenous routes of infection. This mutant, which does not show impaired growth in vitro, is unable to grow in the lung tissue or in blood. Mutation of the response regulator in a 0100993 background results in a strain that is fully virulent intraperitoneally and intravenously but shows decreased levels of bacteremia and increased murine survival following intranasal infection. The ability to grow in the lung tissue is not impaired in this mutant, suggesting that it has an impaired ability to disseminate from the lungs to the systemic circulation. Our data highlight the importance of assessing the contribution of putative virulence factors to the infection process at different sites of infection and provide evidence that virulence determinants can behave very differently based on the genetic background of the bacterial strain. These important findings may be relevant to other bacterial pathogens.

* Corresponding author. Mailing address: Division of Infection and Immunity, Institute of Biomedical and Life Science, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. Phone: (44) 141 330 3749. Fax: (44) 141 330 3727. E-mail: t.mitchell{at}bio.gla.ac.uk.

Editor: J. N. Weiser

Infection and Immunity, August 2003, p. 4405-4413, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4405-4413.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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