The pneumococcal social network

Abstract

Gram-positive bacteria employ an array of secreted peptides to control population-level behaviors in response to environmental cues. We review mechanistic and functional features of secreted peptides produced by the human pathogen Streptococcus pneumoniae . We discuss sequence features, mechanisms of transport, and receptors for 3 major categories of small peptides: the double-glycine peptides, the Rap, Rgg, NprR, PlcR, and PrgX (RRNPP)-binding peptides, and the lanthionine-containing peptides. We highlight the impact of factors that contribute to carriage and pathogenesis, specifically genetic diversity, microbial competition, biofilm development, and environmental adaptation. A recent expansion in pneumococcal peptide studies reveals a complex network of interacting signaling systems where multiple peptides are integrated into the same signaling pathway, allowing multiple points of entry into the pathway and extending information content in new directions. In addition, since peptides are present in the extracellular milieu, there are opportunities for crosstalk, quorum sensing (QS), as well as intra- and interstrain and species interactions. Knowledge on the manner that population-level behaviors contribute to disease provides an avenue for the design and development of anti-infective strategies.

The Rgg1518 transcriptional regulator is a necessary facet of sugar metabolism and virulence in Streptococcus pneumoniae

“…Multiple Rgg regulators have been characterized in pneumococcus and other streptococcal species. The model that emerges is that SHPs are cleaved into active forms during export from precursor polypeptides that are typically shorter than 35 residues (Aggarwal et al., 2014; Aggarwal et al, 2020; Zhi et al., 2018). Multiple streptococcal species export SHPs through an ABC transporter, PptAB, whose homolog in Enterococcus faecalis exports sex pheromones (Chang & Federle, 2016; Varahan et al., 2014).…”

“…The exact mechanism(s) directing SHPs to their transporter remains unclear. The mature peptides are re‐imported into the cell via an oligopeptide permease system, where they interact with the cognate Rgg regulator, altering the cell’s transcriptional state (Aggarwal et al, 2020; Chang et al., 2011; Fleuchot et al., 2011; Zhi et al., 2018).…”

“…Peptide‐mediated pneumococcal QS systems are divided into three main groups based on peptide sequence features, transporters they utilize, and receptors; these are: (i) double glycine processing site peptides, (ii) peptides associated with the RRNPP (Rap, Rgg, NprR, PlcR, and PrgX) superfamily of quorum‐sensing proteins, and (iii) lanthionine‐containing peptides (Aggarwal et al, 2020; Cook et al., 2013).…”

Short-chain fatty acids inhibit the biofilm formation of Streptococcus gordonii through negative regulation of competence-stimulating peptide signaling pathway

“…In S. mutans, CSP can activate autolysin production, such as lytF, sequentially lead- ing to bacterial lysis and promotion of biofilm formation by secreted eDNA from the lysed bacteria (Nagasawa et al, 2020). On the other hand, CSP can evoke the production of the biofilm regulation peptide, such as BriC, resulting in enhanced biofilm formation of Streptococcus pneumoniae (Aggarwal et al, 2020). Therefore, the negatively-regulated CSP pathway by SCFAs in S. gordonii might suppress these pathways.…”

Competence-associated peptide BriC alters fatty acid biosynthesis inStreptococcus pneumoniae

“…Immediately downstream of the pneumococcal FASII locus is the small peptide, BriC ( b iofilm r egulator i nduced by c ompetence). BriC is a ribosomally-synthesized peptide that belongs to the class of double-glycine secreted peptides in pneumococcus (10). The expression of briC is induced directly by ComE, the master regulator of competence, and BriC is secreted via the competence-associated ABC transporter, ComAB (11).…”