Insights into the activity of cefiderocol against PER-2 producing Enterobacterales.
Antimicrob Agents Chemother
; : e0172023, 2024 May 01.
Article
em En
| MEDLINE
| ID: mdl-38690895
ABSTRACT
The PER-2 ß-lactamase is a unique class A enzyme conferring broad spectrum cephalosporin resistance. In this study, we explored the stability of cefiderocol (FDC) against PER-2 ß-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10-12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM-1 s-1, comparable with PER-1 (0.046 µM-1 s-1) and NDM-1 (0.067 µM-1 s-1). In silico models revealed that FDC within the active site of PER-2 demonstrates unique interactions as a result of the inverted Ω loop fold and extension of the ß3-ß4 connecting loop.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Argentina