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Inhibition of OXA-1 beta-lactamase by penems.

ABSTRACT: The partnering of a beta-lactam with a beta-lactamase inhibitor is a highly effective strategy that can be used to combat bacterial resistance to beta-lactam antibiotics mediated by serine beta-lactamases (EC 3.2.5.6). To this end, we tested two novel penem inhibitors against OXA-1, a class D beta-lactamase that is resistant to inactivation by tazobactam. The K(i) of each penem inhibitor for OXA-1 was in the nM range (K(i) of penem 1, 45 +/- 8 nM; K(i) of penem 2, 12 +/- 2 nM). The first-order rate constant for enzyme and inhibitor complex inactivation of penems 1 and 2 for OXA-1 beta-lactamase were 0.13 +/- 0.01 s(-1) and 0.11 +/- 0.01 s(-1), respectively. By using an inhibitor-to-enzyme ratio of 1:1, 100% inactivation was achieved in

SUBMITTER: Bethel CR

PROVIDER: S-EPMC2533510 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Inhibition of OXA-1 beta-lactamase by penems.

Bethel Christopher R CR Distler Anne M AM Ruszczycky Mark W MW Carey Marianne P MP Carey Paul R PR Hujer Andrea M AM Taracila Magda M Helfand Marion S MS Thomson Jodi M JM Kalp Matthew M Anderson Vernon E VE Leonard David A DA Hujer Kristine M KM Abe Takao T Venkatesan Aranapakam M AM Mansour Tarek S TS Bonomo Robert A RA

Antimicrobial agents and chemotherapy 20080616 9

The partnering of a beta-lactam with a beta-lactamase inhibitor is a highly effective strategy that can be used to combat bacterial resistance to beta-lactam antibiotics mediated by serine beta-lactamases (EC 3.2.5.6). To this end, we tested two novel penem inhibitors against OXA-1, a class D beta-lactamase that is resistant to inactivation by tazobactam. The K(i) of each penem inhibitor for OXA-1 was in the nM range (K(i) of penem 1, 45 +/- 8 nM; K(i) of penem 2, 12 +/- 2 nM). The first-order r ...[more]

PMID: 18559643

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