Expression of OXA-Type and SFO-1 β-Lactamases Induces Changes in Peptidoglycan Composition and Affects Bacterial Fitness

beta-Lactamases and penicillin-binding proteins (PBPs) have evolved from a common ancestor. beta-Lactamases are enzymes that degrade beta-lactam antibiotics, whereas PBPs are involved in the synthesis and processing of peptidoglycan, which forms an elastic network in the bacterial cell wall. This study analyzed the interaction between beta-lactamases and peptidoglycan and the impact on fitness and biofilm production. A representative set of all classes of beta-lactamases was cloned in the expression vector pBGS18 under the control of the CTX-M promoter and expressed in Escherichia coli MG1655. The peptidoglycan composition of all clones was evaluated, and quantitative changes were found in E. coli strains expressing OXA-24, OXA-10-like, and SFO-1 (with its upstream regulator AmpR) beta-lactamases; the level of cross-linked muropeptides decreased, and their average length increased. These changes were associated with a statistically significant fitness cost, which was demonstrated in both in vitro and in vivo experiments. The observed changes in peptidoglycan may be explained by the presence of residual DD-endopeptidase activity in these beta-lactamases, which may result in hydrolysis of the peptide cross bridge. The biological cost associated with these changes provides important data regarding the interaction between beta-lactamases and the metabolism of peptidoglycan and may provide an explanation for the epidemiology of these beta-lactamases in Enterobacteriaceae.