Metallo-β-lactamase SMB-1 evolves into a more efficient hydrolase under the selective pressure of meropenem.
Antibiotic resistance
Conformational change
Distal mutation
Evolution
Metallo-β-lactamase SMB-1
Mutational effects
Journal
Journal of inorganic biochemistry
ISSN: 1873-3344
Titre abrégé: J Inorg Biochem
Pays: United States
ID NLM: 7905788
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
18
04
2023
revised:
27
06
2023
accepted:
06
07
2023
medline:
21
8
2023
pubmed:
22
7
2023
entrez:
21
7
2023
Statut:
ppublish
Résumé
Metallo-β-lactamases (MβLs) are the primary mechanism of resistance to carbapenem antibiotics. To elucidate how MβLs have evolved with the introduction and use of antibiotics, the mutation and evolution of SMB-1 from Serratia marcescens were investigated in microbial evolution plates containing discontinuous meropenem (MEM) concentration gradients. The results revealed 2-point mutations, A242G and S257R; 1 double-site mutation, C240G/E258G; and 3 frameshift mutations, M5, M12, and M13, which are all missense mutations situated at the C-terminus. Compared with that of the wild-type (WT), the minimum inhibitory concentrations (MICs) of MEM for A242G, C240G/E258G, M5, M12, and M13 increased at least 120-fold, and that of S257R increased 8-fold. The catalytic efficiency k
Identifiants
pubmed: 37478781
pii: S0162-0134(23)00205-2
doi: 10.1016/j.jinorgbio.2023.112323
pii:
doi:
Substances chimiques
Meropenem
FV9J3JU8B1
beta-Lactamases
EC 3.5.2.6
Anti-Bacterial Agents
0
Carbapenems
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112323Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.