Intra- and interspecies signaling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides

Streptococcus salivarius 20P3 produces a 22-amino-acid residue lantibiotic, designated sativaricin A (SalA), that inhibits the growth of a range of st reptococci, including all strains of Streptococcus pyogenes, Lantibiotic pr oduction is associated with the sal genetic locus comprising salA, the lant ibiotic structural gene; salBCTX genes encoding peptide modification and ex port machinery proteins; and salYKR genes encoding a putative immunity prot ein and two-component sensor-regulator system, Insertional inactivation of salB in S, salivarius 20P3 resulted in abrogation of SalA peptide productio n, of immunity to SalA, and of salA transcription. Addition of exogenous Sa lA peptide to salB mutant cultures induced dose-dependent expression of sal A mRNA (0.2 kb), demonstrating that SalA production was normally autoregula ted, Inactivation of salR encoding the response regulator of the SalKR two- component system led to reduced production of, and immunity to, SalA. The s al genetic locus was also present in S. pyogenes SF370 (M type 1), but beca use of a deletion across the salBCT genes, the corresponding lantibiotic pe ptide, designated SalA1, was not produced, However, in S. pyogenes T1l (M t ype 4) the sal locus gene complement was apparently complete, and active Sa lA1 peptide was synthesized. Exogenously added SalA1 peptide from S, pyogen es Tli induced salA1 transcription in S, pyogenes SF370 and in an isogenic S, pyogenes T11 salB mutant and salA transcription in S. salivarius 20P3 sa lB, Thus, SalA and SalA1 are examples of streptococcal lantibiotics whose p roduction is autoregulated, These peptides act as intra- and interspecies s ignaling molecules, modulating lantibiotic production and possibly influenc ing streptococcal population ecology in the oral cavity.