Artículo
Biochemical and Structural Characterization of CRH-1, a Carbapenemase from Chromobacterium haemolyticum Related to KPC b-Lactamases
Brunetti, Florencia Lourdes
; Ghiglione, Barbara
; Gudeta, Dereje D.; Gutkind, Gabriel Osvaldo
; Guardabassi, Luca; Klinke, Sebastian
; Power, Pablo
Fecha de publicación:
07/2023
Editorial:
American Society for Microbiology
Revista:
Antimicrobial Agents and Chemotherapy
ISSN:
0066-4804
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
KPC-2 is one of the most relevant serine-carbapenemases among the carbapenem-resistant Enterobacterales. We previously isolated from the environmental species Chromobacterium haemolyticum a class A CRH-1 b-lactamase displaying 69% amino acid sequence identity with KPC-2. The objective of this study was to analyze the kinetic behavior and crystallographic structure of this b-lactamase. Our results showed that CRH-1 can hydrolyze penicillins, cephalosporins (except ceftazidime), and carbapenems with similar efficacy compared to KPC-2. Inhibition kinetics showed that CRH-1 is not well inhibited by clavulanic acid, in contrast to efficient inhibition by avibactam (AVI). The high-resolution crystal of the apoenzyme showed that CRH-1 has a similar folding compared to other class A b-lactamases. The CRH-1/ AVI complex showed that AVI adopts a chair conformation, stabilized by hydrogen bonds to Ser70, Ser237, Asn132, and Thr235. Our findings highlight the biochemical and structural similarities of CRH-1 and KPC-2 and the potential clinical impact of this carbapenemase in the event of recruitment by pathogenic bacterial species.
Palabras clave:
AVIBACTAM
,
CARBAPENEMASES
,
KPC-2
,
RESISTOME
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Brunetti, Florencia Lourdes; Ghiglione, Barbara; Gudeta, Dereje D.; Gutkind, Gabriel Osvaldo; Guardabassi, Luca; et al.; Biochemical and Structural Characterization of CRH-1, a Carbapenemase from Chromobacterium haemolyticum Related to KPC b-Lactamases; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 67; 7; 7-2023; 1-12
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