Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9 - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2006

Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9

Résumé

ABSTRACT A random mutagenesis technique was used to predict the evolutionary potential of β-lactamase CTX-M-9 toward the acquisition of improved catalytic activity against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser, which were previously observed in clinical CTX-M enzymes. Additional substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near the active site. The kinetic constants of the three most active mutants revealed two distinct ways of improving catalytic efficiency against ceftazidime. One enzyme had a 17-fold-higher k cat value than CTX-M-9 against ceftazidime. The other two had 75- to 300-fold-lower K m values than CTX-M-9 against ceftazidime. The current emergence of CTX-M β-lactamases with improved activity against ceftazidime may therefore be the beginning of an evolutionary process which might subsequently generate a great diversity of CTX-M-type ceftazidimases.

Dates et versions

hal-03516705 , version 1 (07-01-2022)

Identifiants

Citer

J. Delmas, F. Robin, Frédéric Antonio Carvalho, C. Mongaret, R. Bonnet. Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9. Antimicrobial Agents and Chemotherapy, 2006, 50 (2), pp.731-738. ⟨10.1128/AAC.50.2.731-738.2006⟩. ⟨hal-03516705⟩
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