A Kinetic Study of the Replacement by Site Saturation Mutagenesis of Residue 119 in NDM-1 Metallo-beta-Lactamase

作者：Marcoccia Francesca; Mercuri Paola Sandra; Galleni Moreno; Celenza Giuseppe; Amicosante Gianfranco; Perilli Mariagrazia^*

来源：Antimicrobial Agents and Chemotherapy, 2018, 62(8).

DOI：10.1128/AAC.02541-17;e02541-17

• NDM
• kinetic
• metallo-beta-lactamase

New Delhi metallo-beta-lactamase 1 (NDM-1) is a subclass B1 metallo-beta-lactamase that exhibits a broad spectrum of activity against beta-lactam antibiotics. Here we report the kinetic study of 6 Q119X variants obtained by site-directed mutagenesis of NDM-1. All Q119X variants were able to hydrolyze carbapenems, penicillins and first-, second-, third-, and fourth-generation cephalosporins very efficiently. In particular, Q119E, Q119Y, Q119V, and Q119K mutants showed improvements in k(cat/)K(m) values for penicillins, compared with NDM-1. The catalytic efficiencies of the Q119K variant for benzylpenicillin and carbenicillin were about 65- and 70-fold higher, respectively, than those of NDM-1. The Q119K and 4119Y enzymes had k cat k(cat/)K(m) values for ceftazidime about 25- and 89-fold higher, respectively, than that of NDM-1.

• 出版日期2018-8