Increased Antimicrobial Resistance in a Novel CMY-54 AmpC-Type Enzyme with a GluLeu217-218 Insertion in the Ω-Loop
Pérez-Llarena, Francisco José (Complejo Hospitalario Universitario de A Coruña)
Vázquez-Ucha, Juan Carlos (Complejo Hospitalario Universitario de A Coruña)
Kerff, Frédéric (Université de Liège)
Zamorano, Laura (Hospital Universitari Son Dureta (Palma de Mallorca, Balears))
Miró, Elisenda (Institut d'Investigació Biomèdica Sant Pau)
Cabral, María Póvoa (Complejo Hospitalario Universitario de A Coruña)
Fleites, Ana (Universidad de Oviedo)
Lantero, Marta (Universidad de Oviedo)
Martínez-Martínez, Luis (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Oliver, Antonio (Hospital Universitari Son Dureta (Palma de Mallorca, Balears))
Galleni, Moreno (Université de Liège)
Navarro Risueño, Ferran (Institut d'Investigació Biomèdica Sant Pau)
Beceiro, Alejandro (Complejo Hospitalario Universitario de A Coruña)
Bou, German (Complejo Hospitalario Universitario de A Coruña)

Date:	2018
Description:	7 pàg.
Abstract:	During a Spanish surveillance study, a natural variant of a CMY-type β-lactamase related to CMY-2 with a GluLeu217-218 insertion in the Ω-loop (designated CMY-54) was found to increase the minimum inhibitory concentractions to β-lactams in a clinical strain of Escherichia coli. The aim of this study was to characterize CMY-54 by genetic, microbiological, and biochemical analysis. The blaCMY-54 gene is encoded by a plasmid of around 100 kb that hybridizes with K and FIB probes. The genetic context of blaCMY-54 and blaCMY-2 genes was found to be very similar. E. coli expressing CMY-54 under isogenic conditions showed a clear fourfold to eightfold increase in MICs to penicillins, cefotaxime, ceftazidime, and aztreonam compared with CMY-2. The catalytic efficiencies of pure CMY-2 and CMY-54 proteins correlated with their microbiological parameters. CMY-2 protein was more resistant to thermal denaturation than CMY-54, indicating that the Ω-loop of CMY-54 may be wider and more relaxed and probably enables better accommodation of these antimicrobials. Otherwise, the higher stabilization of CMY-2 may induce a slight reduction of the dynamics of this enzyme and primarily affect the hydrolysis of some of the bulkiest antibiotics. In summary, the GluLeu217-218 insertion observed in CMY-54 compared to CMY-2 produces a β-lactamase with a distinctive catalytic efficacy for β-lactam antimicrobials likely caused by an increased flexibility slightly affecting the active site shape, highlighting the relevance of single mutations on the hydrolytic spectrum in class C β-lactamases.
Grants:	European Commission 278232 Ministerio de Economía y Competitividad RD16/0016/0006 Instituto de Salud Carlos III PI12/00552 Instituto de Salud Carlos III PI15/00860 Instituto de Salud Carlos III CP13/00226 Instituto de Salud Carlos III PI14/00059
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Antimicrobial ; Escherichia coli ; Extended-spectrum ; Mechanisms ; Microbial drug resistance
Published in:	Microbial Drug Resistance, Vol. 24, Issue 5 (June 2018) , p. 527-533, ISSN 1931-8448

DOI: 10.1089/mdr.2017.0017
PMID: 28665771

Postprint 23 p, 719.8 KB

The record appears in these collections:
Articles > Research articles
Articles > Published articles