Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity.

Abstract : Pneumococcus resists β-lactams by expressing variants of its target enzymes, the penicillin-binding proteins (PBPs), with many amino acid substitutions. Up to 10% of the sequence can be modified. These altered PBPs have a much reduced reactivity with the drugs but retain their physiological activity of cross-linking the peptidoglycan, the major constituent of the bacterial cell wall. However, because β-lactams are chemical and structural mimics of the natural substrate, resistance mediated by altered PBPs raises the following paradox: how PBPs that react poorly with the drugs maintain a sufficient level of activity with the physiological substrate. This question is addressed for the first time in this study, which compares the peptidoglycan cross-linking activity of PBP2b from susceptible and resistant strains with their inhibition by different β-lactams. Unexpectedly, the enzymatic activity of the variants did not correlate with their antibiotic reactivity. This finding indicates that some of the numerous amino acid substitutions were selected to restore a viable level of enzymatic activity by a compensatory molecular mechanism.
Type de document :
Article dans une revue
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2017, 292 (7), pp.2854-2865. 〈10.1074/jbc.M116.764696〉
Liste complète des métadonnées

http://hal.univ-grenoble-alpes.fr/hal-01497668
Contributeur : Frank Thomas <>
Soumis le : mercredi 29 mars 2017 - 09:22:50
Dernière modification le : jeudi 11 janvier 2018 - 06:15:24

Identifiants

Collections

Citation

Philippe Calvez, Eefjan Breukink, David I Roper, Mélanie Dib, Carlos Contreras-Martel, et al.. Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2017, 292 (7), pp.2854-2865. 〈10.1074/jbc.M116.764696〉. 〈hal-01497668〉

Partager

Métriques

Consultations de la notice

74