Interspecies Communication among Commensal and Pathogenic Streptococci

UNLABELLED Quorum sensing (QS) regulates diverse and coordinated behaviors in bacteria, including the production of virulence factors, biofilm formation, sporulation, and competence development. It is now established that some streptococci utilize Rgg-type proteins in concert with short hydrophobic peptides (SHPs) to mediate QS, and sequence analysis reveals that several streptococcal species contain highly homologous Rgg/SHP pairs. In group A streptococcus (GAS), two SHPs (SHP2 and SHP3 [SHP2/3]) were previously identified to be important in GAS biofilm formation. SHP2/3 are detected by two antagonistic regulators, Rgg2 and Rgg3, which control expression of the shp genes. In group B streptococcus (GBS), RovS is a known virulence gene regulator and ortholog of Rgg2, whereas no apparent Rgg3 homolog exists. Adjacent to rovS is a gene (shp1520) encoding a peptide nearly identical to SHP2. Using isogenic mutant strains and transcriptional reporters, we confirmed that RovS/SHP1520 comprise a QS circuit in GBS. More important, we performed experiments demonstrating that production and secretion of SHP1520 by GBS can modulate Rgg2/3-regulated gene expression in GAS in trans; likewise, SHP2/3 production by GAS can stimulate RovS-mediated gene regulation in GBS. An isolate of Streptococcus dysgalactiae subsp. equisimilis also produced a secreted factor capable of simulating the QS circuits of both GAS and GBS, and sequencing confirms the presence of an orthologous Rgg2/SHP2 pair in this species as well. To our knowledge, this is the first documented case of bidirectional signaling between streptococcal species in coculture and suggests a role for orthologous Rgg/SHP systems in interspecies communication between important human pathogens. IMPORTANCE Pathogenic streptococci, such as group A (GAS) and group B (GBS) streptococcus, are able to persist in the human body without causing disease but become pathogenic under certain conditions that are not fully characterized. Environmental cues and interspecies signaling between members of the human flora likely play an important role in the transition to a disease state. Since quorum-sensing (QS) peptides have been consistently shown to regulate virulence factor production in pathogenic species, the ability of bacteria to signal via these peptides may prove to be an important link between the carrier and pathogenic states. Here we provide evidence of a bidirectional QS system between GAS, GBS, and Streptococcus dysgalactiae subsp. equisimilis, demonstrating the possibility of evolved communication systems between human pathogens.