Streptococci are prevalent in animal and human microbiomes. These organisms produce a vast array of small peptides that modulate complex functions within the cell such as quorum sensing, virulence, and metabolism. Transcriptional regulators are central to this process, of which Rgg transcriptional regulators hold prominence in streptococci. These systems are controlled by peptides known as SHPs (short hydrophobic peptides) and LCPs (leaderless communication peptides). Also known as Rgg/SHP quorum sensing (QS) systems, they are ubiquitous across streptococcal species and regulate cellular competence, metabolic programs, virulence, and facilitate colonization of host species. It has been recently demonstrated that Rgg/SHP QS systems can also regulate the production of natural products known as RaS-RiPPs (Radical S -adenosylmethionine enzyme Ribosomally translated and Post-translationally modified Peptides). RaS-RiPPs are widespread in streptococci with sixteen current subfamilies. Some of these natural products possess inhibitory properties while others’ functions are currently unknown. We provide here a review of Rgg/SHP systems within streptococci, the complexities and characterized functions of RaS-RiPPs, as well as the connection between Rgg/SHP and RaS-RiPPs. We also provide a brief overview of competence in streptococci, given the relevance of these systems to peptide signaling in this genus.
