Genetic, Biochemical, and Structural Characterization of CMY-136 Beta-Lactamase, a Peculiar CMY-2 Variant - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue ACS Infectious Diseases Année : 2019

Genetic, Biochemical, and Structural Characterization of CMY-136 Beta-Lactamase, a Peculiar CMY-2 Variant

Résumé

With the widespread use and abuse of antibiotics for the past decades, antimicrobial resistance poses a serious threat to public health nowadays. β-Lactams are the most used antibiotics, and β-lactamases are the most widespread resistance mechanism. Class C β-lactamases, also known as cephalosporinases, usually do not hydrolyze the latest and most potent β-lactams, expanded spectrum cephalosporins and carbapenems. However, the recent emergence of extended-spectrum AmpC cephalosporinases, their resistance to inhibition by classic β-lactamase inhibitors, and the fact that they can contribute to carbapenem resistance when paired with impermeability mechanisms, means that these enzymes may still prove worrisome in the future. Here we report and characterize the CMY-136 β-lactamase, a Y221H point mutant derivative of CMY-2. CMY-136 confers an increased level of resistance to ticarcillin, cefuroxime, cefotaxime, and ceftolozane/tazobactam. It is also capable of hydrolyzing ticarcillin and cloxacillin, which act as inhibitors of CMY-2. X-ray crystallography and modeling experiments suggest that the hydrolytic profile alterations seem to be the result of an increased flexibility and altered conformation of the Ω-loop, caused by the Y221H mutation.
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hal-02119851 , version 1 (10-03-2021)

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Agustin Zavala, Pascal ́ Retailleau, Eddy Elisée, Bogdan Iorga, Thierry Naas. Genetic, Biochemical, and Structural Characterization of CMY-136 Beta-Lactamase, a Peculiar CMY-2 Variant. ACS Infectious Diseases, 2019, 5 (4), pp.528-538. ⟨10.1021/acsinfecdis.8b00240⟩. ⟨hal-02119851⟩
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