Laboratory Variants GES G170L , GES G170K , and GES G170H Increase Carbapenem Hydrolysis and Confer Resistance to Clavulanic Acid-Reference-Cited by-同舟云学术

Laboratory Variants GES G170L , GES G170K , and GES G170H Increase Carbapenem Hydrolysis and Confer Resistance to Clavulanic Acid

Published:2021-05-18 Issue:6 Volume:65 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Piccirilli Alessandra¹,Mercuri Paola Sandra²,Segatore Bernardetta¹,Galleni Moreno²,Brisdelli Fabrizia¹,Kerff Frédéric³,Amicosante Gianfranco¹,Perilli Mariagrazia¹^ORCID

Affiliation:

1. Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell'Aquila, L'Aquila, Italy

2. Macromolécules Biologiques and Centre d’Ingénierie des Protéines, InBioS, Université de Liège, Liège, Belgium

3. Cristallographie des Macromolécules Biologiques, Centre d’Ingénierie des Protéines, InBioS, Université de Liège, Liège, Belgium

Abstract

The Guiana extended-spectrum (GES) β-lactamase GES G170H , GES G170L , and GES G170K mutants showed k cat , K m , and k cat / K m values very dissimilar to those of GES-1 and GES-5. The enhancement of the hydrolytic activity against carbapenems is potentially due to a shift of the substrate in the active site that provides better positioning of the deacylating water molecule caused by the presence of the imidazole ring of H170 and of the long side chain of K170 and L170.

Funder

Università degli Studi dell'Aquila

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01931-20

Reference19 articles.

1. Epidemiology of Carbapenemase-Producing Klebsiella pneumoniae in a Hospital, Portugal

2. Nosocomial Spread of Ceftazidime-Resistant Klebsiella pneumoniae Strains Producing a Novel Class A β-Lactamase, GES-3, in a Neonatal Intensive Care Unit in Japan

3. Structural and Functional Aspects of Class A Carbapenemases

4. Genetic and biochemical characterization of GES-16, a new GES-type β-lactamase with carbapenemase activity in Serratia marcescens

5. Structural Basis for Carbapenem-Hydrolyzing Mechanisms of Carbapenemases Conferring Antibiotic Resistance

Cited by 1 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. A Two Amino Acid Duplication, L167E168, in the Ω-Loop Drastically Decreases Carbapenemase Activity of KPC-53, a Natural Class A β-Lactamase;Antimicrobial Agents and Chemotherapy;2022-06-21