title: Expression of OXA-type and SFO-1 β-lactamases induces changes in peptidoglycan composition and affects bacterial fitness.
abstract: β-Lactamases and penicillin-binding proteins (PBPs) have evolved from a common ancestor. β-Lactamases are enzymes that degrade β-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 β-lactamases and peptidoglycan and the impact on fitness and biofilm production. A representative set of all classes of β-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) β-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 β-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 β-lactamases and the metabolism of peptidoglycan and may provide an explanation for the epidemiology of these β-lactamases in Enterobacteriaceae.
authors.affiliation: Servicio de Microbiología, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández
authors.forename: Astrid
authors.initials: A
authors.lastname: Pérez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ayala
authors.forename: Susana
authors.initials: S
authors.lastname: Mallo
authors.forename: Soraya
authors.initials: S
authors.lastname: Rumbo-Feal
authors.forename: Maria
authors.initials: M
authors.lastname: Tomás
authors.forename: Margarita
authors.initials: M
authors.lastname: Poza
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
mesh_terms: D000818:Animals; D018441:Biofilms; D003001:Cloning, Molecular; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D005260:Female; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010457:Peptidoglycan / Q000737:chemistry* / Q000378:metabolism; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D010457:Peptidoglycan; C425107:beta-lactamase OXA-10; C118316:beta-lactamase SFO-1; D001618:beta-Lactamases; C410345:beta-lactamase OXA-24