Inactivation of the srtA gene in Streptococcus gordonii inhibits cell wallanchoring of surface proteins and decreases in vitro and in vivo adhesion

The srtA gene product, SrtA, has been shown tea be required for cell wall a nchoring of protein A as well as virulence in the pathogenic bacterium Stap hylococcus aureus. There are five major mechanisms for displaying proteins at the surface of gram-positive bacteria (P. Cossart and R. Jonquieres, Pro c. Natl. Acad. Sci. USA 97:5013-5015, 2000). However, since many of the kno wn surface proteins of gram-positive bacteria are believed to be exported a nd anchored via the sortase pathway, it was of interest to determine if srt A plays a similar role in other gram-positive bacteria. To that end, the sr tA gene in the human oral commensal organism Streptococcus gordonii was ins ertionally inactivated. The srtA mutant S. gordonii exhibited a marked redu ction in quantity of a specific anchored surface protein. Furthermore, the srtA mutant had reduced binding to immobilized human fibronectin and had a decreased ability to colonize the oral mucosa of mice. Taken together, thes e results suggest that the activity of SrtA plays an Important role in the biology of nonpathogenic as well as pathogenic gram-positive cocci.