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Infection and Immunity, July 2008, p. 3187-3196, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00054-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Convergence of Regulatory Networks on the Pilus Locus of Streptococcus pneumoniae ^,

Jason W. Rosch, Beth Mann, Justin Thornton, Jack Sublett, and Elaine Tuomanen^*

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Received 15 January 2008/ Returned for modification 5 March 2008/ Accepted 19 April 2008

The rlrA pilus locus of Streptococcus pneumoniae is an example of a pathogenicity island acquired through genetic recombination. Many acquired genetic elements commandeer preexisting networks of the new organism for transcriptional regulation. We hypothesized that the rlrA locus has integrated into transcriptional regulatory networks controlling expression of virulence factors important in adhesion and invasion. To test this hypothesis, we determined the impact on pilus expression of known regulators controlling adherence, including the two-component systems CbpR/S and HK/RR03 and the transcriptional regulators of divalent cation transporters MerR and PsaR in vitro and in vivo. It was determined that the pilus locus is down-regulated by preexisting networks designed for adhesion and cation transport/response and that its regulation occurs through RlrA. The pilus locus was found to participate in invasion specifically restricted to lung epithelial cells in vitro. While expression of pili had only a small effect on virulence with an intranasal infection model, pili were critically important with an intratracheal infection model. Thus, expression of pili appears to have become integrated into the regulatory circuits for lung-specific invasion by pneumococci.

Published ahead of print on 28 April 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

These authors contributed equally to this work.

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