A unique class of Zn²⁺-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile.

ABSTRACT: Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C. difficile has four different PBPs (PBP1-3 and SpoVD) with various roles in growth and spore formation, and their specific links to β-lactam resistance in this pathogen are underexplored. Here, we show that PBP2 (known to be essential for vegetative growth) is the primary bactericidal target for β-lactams in C. difficile. PBP2 is insensitive to cephalosporin inhibition, and this appears to be the main basis for cephalosporin resistance in this organism. We determine crystal structures of C. diff

SUBMITTER: Sacco MD 

PROVIDER: S-EPMC9334274 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature