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Journal of Bacteriology, August 2007, p. 5591-5600, Vol. 189, No. 15
0021-9193/07/$08.00+0     doi:10.1128/JB.00335-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Pneumococcal Two-Component Signal Transduction System RR/HK06 Regulates CbpA and PspA by Two Distinct Mechanisms{triangledown}

Alistair J. Standish, Uwe H. Stroeher, and James C. Paton*

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia

Received 6 March 2007/ Accepted 18 May 2007

We have previously shown that CbpA, a major pneumococcal virulence factor, is regulated by the two-component signal transduction system RR/HK06 (A. J. Standish, U. H. Stroeher, and J. C. Paton, Proc. Natl. Acad. Sci. USA 102:7701-7706, 2005). However, additional unidentified regulated factors appeared to be responsible for differences in adherence and the ability of Streptococcus pneumoniae to cause disease in a mouse model. Here, we identified a number of other regulated genes by overexpressing the system. cbpA, along with a cotranscribed upstream gene, showed substantial increases in expression when RR06 was overexpressed in S. pneumoniae strains D39 and TIGR4. However, there were no other similarities between these strains. In D39, rr06 overexpression decreased expression of numerous factors, including the major virulence factor gene pspA. Further investigation of cbpA regulation by RR/HK06, using mutants with mutations in both HK06 and RR06, suggested that rather than the norm, cbpA transcription was activated when RR06 was in the nonphosphorylated form. Although other factors, such as pspA and gls24, are regulated by this system, these genes appear to be repressed when RR06 is in its phosphorylated form.

* Corresponding author. Mailing address: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, S.A. 5005, Australia. Phone: 61-8-83035929. Fax: 61-8-83033262. E-mail: james.paton{at}adelaide.edu.au

{triangledown} Published ahead of print on 25 May 2007.

Journal of Bacteriology, August 2007, p. 5591-5600, Vol. 189, No. 15
0021-9193/07/$08.00+0     doi:10.1128/JB.00335-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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