Molecular gatekeepers: how peptide maturation molecules coordinate cell-cell communication in Streptococcus pneumoniae

ABSTRACT: Cell-cell communication systems enable populations to regulate behavior via modifications in gene expression. In Gram-positive bacteria, these systems are often composed of secreted, signaling peptides that disperse across the population and interact with cognate transcriptional regulators. While cells generally possess multiple such systems, there is a gap in knowledge regarding molecular mechanisms that coordinate these systems to allow for optimization of phenotypic responses. The human pathogen Streptococcus pneumoniae (Spn) encodes several cell-cell communication systems, notably multiple members of the Rgg/SHP and the Tpr/Phr family. Previous studies have characterized their individual regulatory networks and established their importance in Spn virulence and until now, these two signaling families were thought to work independently. Our study provides the molecular link between Rgg/SHP and TprA/PhrA systems by demonstrating that conserved peptide maturation molecules are integral to the coordination of both systems in Spn. We reveal that the ABC transporter PptAB and the transmembrane enzyme Eep display a dual mode of action, simultaneously activating the Rgg/SHP systems and repressing the TprA/PhrA system. Specifically, they regulate the respective precursor peptides (SHP and PhrA) before these leave the cell. This dual function leads to temporal coordination of these systems producing an overlap between their respective regulons during host cell infection. Thus, we have identified a single molecular mechanism that targets diverse cell-cell communication systems. Moreover, the signaling systems and peptide maturation molecules are also encoded by closely related species and other Gram-positive bacteria suggesting this coordination mechanism may have applications across species boundaries.

ORGANISM(S): Streptococcus pneumoniae

PROVIDER: GSE268602 | GEO | 2024/07/01

REPOSITORIES: GEO