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Antimicrobial Agents and Chemotherapy, July 1999, p. 1743-1746, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Class C beta -Lactamases Operate at the Diffusion Limit for Turnover of Their Preferred Cephalosporin Substrates

Alexey Bulychev and Shahriar Mobashery*

Department of Chemistry, Wayne State University, Detroit, Michigan 48202

Received 4 February 1999/Returned for modification 6 April 1999/Accepted 4 May 1999

It has been suggested that class C beta -lactamases have evolved to carry out a metabolic reaction other than hydrolysis of beta -lactam antibiotics. It is demonstrated in the present study that the class C beta -lactamase from Enterobacter cloacae P99 has reached the diffusion limit in its ability to hydrolyze its preferred cephalosporin substrates. The increase in the solution viscosity by addition of a microviscogen (sucrose) caused the decline in the parameter kcat/Km for hydrolysis of cephaloridine and cephalosporin C (approximately 2.5-fold at a relative viscosity of 2.9). A similar increase in viscosity has no effect on the turnover rate of the poorer substrates cefepime and penicillin G. Addition of a macroviscogen (polyethylene glycol) to the reaction mixture did not change the rate of turnover for any of the substrates tested because in this case the viscogen would not interfere with the motion of small molecules, as was expected. Therefore, it would appear that the driving force behind the evolution of this class C beta -lactamase and, in principle, other enzymes of this class is indeed the functional reaction of this enzyme as a drug resistance factor.

* Corresponding author. Mailing address: Department of Chemistry, Wayne State University, Detroit, MI 48202. Phone: (313) 577-3924. Fax: (313) 577-8822. E-mail: som{at}mobashery.chem.wayne.edu.

Antimicrobial Agents and Chemotherapy, July 1999, p. 1743-1746, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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