B-147. The Enterococcus Faecalis Membrane-Embedded Metalloprotease, CylI, Inactivates Cytolysin Toxin by Cleavage of the Large Toxin Subunit, CylLL

S. M. McBride, K. Carniol, A. Spoering, M. Gilmore;
Schepens Eye Res. Inst., Harvard Med. Sch., Boston, MA.

The virulence toxin secreted by the Gram-positive pathogen Enterococcus faecalis kills both eukaryotic and prokaryotic cells. Toxin activity is conferred by the two structural cytolysin subunits, CylLL and CylLS. Strains of E. faecalis that synthesize cytolysin also make an immunity factor to prevent self-killing. This immunity factor is encoded by the cylI gene. The 327 residue CylI polypeptide does not share homology with any known toxin immunity factors, however it does possess a motif share with membrane-embedded metaolloproteases. Here we provide evidence that CylI is a membrane-embedded metalloprotease that protects against cytolysin activity by inactivation of the large cytolysin toxin structural subunit. This is the first bacterial immunity factor found to function as a protease, and identifies a previously unrecognized role for the functionally diverse family of membrane metalloproteases that are found across phylogenies.