Streptococcus pneumoniae S protein activates PBP1a to regulate peptidoglycan remodelling and cell division.

Class A penicillin-binding proteins (aPBPs) are involved in the biosynthesis and remodelling of peptidoglycan (PG). The human bacterial pathogen Streptococcus pneumoniae produces three aPBPs, which are regulated to maintain the bacterium's ovoid shape. Evidence suggests that PBP1a and PBP2a activities are closely coordinated; however, their precise functions remain unclear. Here we characterized the pneumococcal S protein, which contains a LysM-PG-binding domain and a GpsB-interacting domain. Using S protein fusion constructs or mutant bacterial strains, we show that S protein localizes to the division ring and is required to prevent premature cell lysis and minicell formation due to aberrant division site placement. S protein interacts with PBP1a and activates its PG synthesis activity. Co-immunoprecipitation experiments combined with biochemical, genetic, structural prediction and microscopy analyses suggest that S protein is part of a larger multiprotein complex containing aPBPs and PG-modifying enzymes, and coordinated by the scaffolding protein GpsB. Together, these findings suggest that a GpsB-associated complex orchestrates PG biosynthesis and remodelling in S. pneumoniae.