Downstream of a second promoter was a small ORF encoding a potential competence pheromone propeptide that we later designated ComS to highlight its homology with the ComS of S. thermophilus and S. mutans. In the bovis, pyogenes and mutans species of streptococci the competence propeptide sequence is highly variable except for the presence of two adjacent tryptophan residues near the C terminus which appear to be essential for competence induction in S. mutans. In S. suis serotype 2 there are also two tryptophan residues near the C-terminus of the competence peptide but they are separated by two different amino acid residues. As the full length 21-aa ComS propeptide of S. suis did not induce competence for DNA transformation under our standard conditions, we hypothesized that the propeptide needed to be processed into a biologically active form, and thus tested several N- terminal deletion variants. Competence induction was optimal using the C-terminal 9 residues of ComS, suggesting that the propeptide contains specific N-terminal sequences that determine processing and secretion steps. In S. mutans, ComS is processed to form a 7-aa comX inducing peptide, which has been detected extracellularly in chemically defined medium. Poor activity of the propeptide ComS itself indicates that it is processed before or during transport across the cytoplasmic membrane, via unknown mechanisms. It is likely that a similar mechanism occurs in S. suis because truncated variants of ComS but not the full length peptide induce competence for transformation when added exogenously. Moreover S. suis contains a SRT3109 predicted orthologue of S. thermophilus Eep, data not shown, which is involved in processing of the competence peptide. The putative ComS GRA Ex-25 inhibitor propeptides of S. pyogenes, S. uberis, S. dysgalactiae and S. equi possess a basic N-terminus and hydrophobic central core, which are characteristic of type 2 signal secretion leaders, although the polar C-terminus is absent. In contrast the ComS propeptides encoded by S. suis and S. mutans are hydrophobic shorter versions of those found in streptococci in the pyogenic and bovis groups and do not contain Nor C-terminal signatures associated with signal secretion leaders.