The sil Locus in Streptococcus Anginosus Group: Interspecies Competition and a Hotspot of Genetic Diversity

The Streptococcus Invasion Locus (Sil) was first described in Streptococcus pyogenes and Streptococcus pneumoniae, where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes. Comparative analysis of 42 Streptococcus Anginosus/Milleri Group (SAG) genomes reveals this to be a hot spot for genomic variability. A cluster of bacteriocin/immunity genes is found adjacent to the sil system in most SAG isolates (typically 6–10 per strain). In addition, there were two distinct SilCR peptides identified in this group, denoted here as SilCR(SAG-A) and SilCR(SAG-B), with corresponding alleles in silB. Our analysis of the 42 sil loci showed that SilCR(SAG-A) is only found in Streptococcus intermedius while all three species can carry SilCR(SAG-B). In S. intermedius B196, a putative SilA operator is located upstream of bacteriocin gene clusters, implicating the sil system in regulation of microbe–microbe interactions at mucosal surfaces where the group resides. We demonstrate that S. intermedius B196 responds to its cognate SilCR(SAG-A), and, less effectively, to SilCR(SAG-B) released by other Anginosus group members, to produce putative bacteriocins and inhibit the growth of a sensitive strain of S. constellatus.