Cefdinir binding to a class-A β-lactamase revealed by serial cryo-crystallography

Abstract

One of the most common resistance mechanisms against antibiotics employed by Gram-negative bacteria involves the production of {beta}-lactamases, resulting in rapid hydrolysis of the antibiotic. Extensive use of the early generation cephalosporins led to the rise of extended-spectrum {beta}-lactamases (ESBLs) like CTX-Ms. Cefdinir is an extended-spectrum third-generation cephalosporin administered since the late 90s; despite this, there is no reported 3D-structure of the antibiotic bound to any {beta}-lactamase or Penicillin-Binding-Protein (PBP) in the PDB. Here we report the X-ray crystallographic structure of Cefdinir-bound CTX-M-14 E166A mutant obtained via serial cryo-crystallography (cryo-SSX). SynopsisSerial cryo-crystallography reveals the structure of the extended spectrum {beta}-lactamase CTX-M-14, in complex with the third-generation cephalosporin antibiotic Cefdinir.