Penicillin-binding protein 1a promotes resistance of group B streptococcus to antimicrobial peptides.

Evasion of host immune defenses is critical for the progression of invasive infections caused by the leading neonatal pathogen, group B streptococcus (GBS). Upon characterizing the factors required for virulence in a neonatal rat sepsis model, we found that a surface-associated penicillin-binding protein (PBP1a), encoded by ponA, played an essential role in resistance of GBS to phagocytic clearance. In order to elucidate how PBP1a promotes resistance to innate immunity, we compared the susceptibility of wild-type GBS and an isogenic ponA mutant to the bactericidal components of human neutrophils. The isogenic strains were found to be equally capable of blocking complement activation on the bacterial surface and equally associated with phagocytes and susceptible to oxidative killing. In contrast, the ponA mutant was significantly more susceptible to killing by cationic antimicrobial peptides (AMPs) of the cathelicidin and defensin families, which are now recognized as integral components of innate host defense against invasive bacterial infection. These observations may help explain the sensitivity to phagocytic killing and attenuated virulence of the ponA mutant. This novel function for PBP1a in promoting resistance of GBS to AMP did not involve an alteration in bacterial surface charge or peptidoglycan cross-linking. While the peptidoglycan polymerization and cross-linking activity of PBPs are essential for bacterial survival, our study is the first to identify a role for a PBP in resistance to host AMPs.