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

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

^* To whom correspondence should be addressed. Email: james.paton{at}adelaide.edu.au.

	Abstract

We have previously shown that CbpA, a major pneumococcal virulence factor, is regulated by the two-component signal transduction system RR/HK06. However, additional un-identified 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 identify a number of other regulated genes by over-expressing the system. cbpA, along with its co-transcribed upstream gene, showed substantial increases in expression when RR06 was over-expressed in both S. pneumoniae strains D39 and TIGR4. However, there were no other similarities between the strains. In D39, rr06 over-expression decreased expression of numerous factors including the major virulence factor pspA. Further investigation of cbpA regulation by RR/HK06, using mutants in both HK06 and RR06, suggested that rather than the norm, cbpA transcription was activated when RR06 was in the non-phosphorylated 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.