A Genetic Determinant in Streptococcus gordonii Challis Encodes a Peptide with Activity Similar to That of Enterococcal Sex Pheromone cAM373, Which Facilitates Intergeneric DNA Transfer

Enterococcus faecalis strains secrete multiple peptides representing different sex pheromones that induce mating responses by bacteria carrying specific conjugative plasmids. The pheromone cAM373, which induces a response by the enterococcal plasmid pAM373, has been of interest because a similar activity is also secreted byStreptococcus gordonii andStaphylococcus aureus . The potential to facilitate intergeneric DNA transfer fromE. faecalis is of concern because of extensive multiple antibiotic resistance, including vancomycin resistance, that has emerged among enterococci in recent years. Here, we characterize the related pheromone determinant inS. gordonii and show that the peptide it encodes,gordonii -cAM373, does indeed induce transfer of plasmid DNA fromE. faecalis intoS. gordonii . The streptococcal determinantcamG encodes a lipoprotein with a leader sequence, the last 7 residues of which represent thegordonii -cAM373 heptapeptide SVFILAA. Synthetic forms of the peptide had activity similar to that of the enterococcal cAM373 AIFILAS. The lipoprotein moiety bore no resemblance to the lipoprotein encoded byE. faecalis . We also identified determinants inS. gordonii encoding a signal peptidase and an Eep-like zinc metalloprotease (lspA andeep , respectively) similar to those involved in processing certain pheromone precursors inE. faecalis . Mutations generated incamG ,lspA , andeep each resulted in the ablation ofgordonii -cAM373 activity in culture supernatants. This is the first genetic analysis of a potential sex pheromone system in a commensal oral streptococcal species, which may have implications for intergeneric gene acquisition in oral biofilms.