Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae.

is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in Although Rgg presented greater similarity to a repressor in , autoinducing assays and genetic mutation analysis revealed that in Rgg acts as an activator. Transcriptome analysis showed that in addition to , the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in indicated that lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the mutant under normal or antibiotic stress conditions. The SHP was, however, fully functional in promoting cross-species communication and increasing surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a reporter strain. In competitive assays, a slight advantage was observed for the mutants. We conclude that the Rgg/SHP system in regulates the expression of its own and activates an Rgg/SHP system in that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions. Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in , a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with , a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in are likely part of a futile cycle of activation, the target genes in are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.