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Journal of Bacteriology, August 2004, p. 5258-5266, Vol. 186, No. 16
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.16.5258-5266.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Control of Virulence by the Two-Component System CiaR/H Is Mediated via HtrA, a Major Virulence Factor of Streptococcus pneumoniae

Yasser Musa Ibrahim, Alison R. Kerr, Jackie McCluskey, and Tim J. Mitchell*

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

Received 19 February 2004/ Accepted 5 May 2004

The CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae. The system is known to regulate many genes, including that for high-temperature requirement A (HtrA). This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats. We reported previously that deletion of the gene for HtrA made the pneumococcal strains much less virulent in mouse models, less able to grow at higher temperatures, and more sensitive to oxidative stress. In this report, we show that the growth phenotype as well as sensitivity to oxidative stress of {Delta}ciaR mutant was very similar to that of a {Delta}htrA mutant and that the expression of the HtrA protein was reduced in a ciaR-null mutant. Both the in vitro phenotype and the reduced virulence of {Delta}ciaR mutant could be restored by increasing the expression of HtrA.

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

Journal of Bacteriology, August 2004, p. 5258-5266, Vol. 186, No. 16
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.16.5258-5266.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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