Structural insight into YcbB-mediated beta-lactam resistance in Escherichia coli

• DOI: 10.1038/s41467-019-09507-0
• Publication Date: 2019-04-23T10:04:03Z
• Authors: Nathanael A. Caveney; Guillermo Caballero; Henri Voedts; Ana Niciforovic; Liam J. Worrall; Marija Vuckovic; Matthieu Fonvielle; Jean-Emmanuel Hug...; Michel Arthur; Natalie C. J. Str...
• Keywords: Penicillin binding proteins; Transferase; Peptidyl transferase; Mechanism of Action

Abstract The bacterial cell wall plays a crucial role in viability and is an important drug target. In Escherichia coli , the peptidoglycan crosslinking reaction to form primarily carried out by penicillin-binding proteins that catalyse D,D-transpeptidase activity. However, alternate mechanism involving L,D-transpeptidase YcbB can lead bypass of D,D-transpeptidation beta-lactam resistance. Here, we show crystallographic structure consists conserved catalytic domain decorated with subdomain on dynamic substrate capping loop, peptidoglycan-binding large scaffolding domains. Meropenem acylation gives insight into mode inhibition carbapenems, singular antibiotic class significant activity against L,D-transpeptidases. We also report PBP5-meropenem compare interactions mediating inhibition. Additionally, probe interaction network this pathway assay resistance vivo. Our results provide structural insights action L,D-transpeptidation, YcbB-mediated