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Antimicrobial Agents and Chemotherapy, July 1999, p. 1574-1577, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

DNA Cleavage Activities of Staphylococcus aureus Gyrase and Topoisomerase IV Stimulated by Quinolones and 2-Pyridones

Anne Y. C. Saiki, Linus L. Shen,* Chih-Ming Chen, John Baranowski, and Claude G. Lerner*

Abbott Laboratories, Infectious Disease Research, Abbott Park, Illinois 60064-3537

Received 24 November 1998/Returned for modification 5 January 1999/Accepted 12 April 1999

We have cloned Staphylococcus aureus DNA gyrase and topoisomerase IV and expressed them in Escherichia coli as polyhistidine-tagged proteins to facilitate purification and eliminate contamination by host enzymes. The enzyme preparations had specific activities similar to previously reported values. Potassium glutamate (K-Glu) stimulated the drug-induced DNA cleavage activity and was optimal between 100 and 200 mM for gyrase and peaked at 100 mM for topoisomerase IV. Higher concentrations of K-Glu inhibited the cleavage activities of both enzymes. Using a common buffer system containing 100 mM K-Glu, we tested the enzyme-mediated DNA cleavage activities of both gyrase and topoisomerase IV with oxolinic acid, norfloxacin, ciprofloxacin, trovafloxacin, clinafloxacin, and the 2-pyridone ABT-719. As expected, all drugs tested demonstrated greater potency against topoisomerase IV than against gyrase. In addition, cleavage activity was found to correlate well with antibacterial activity.

* Corresponding author. Mailing address: Abbott Laboratories, Infectious Disease Research, D47P/AP52-1N, 200 Abbott Park Rd., Abbott Park, IL 60064-3537. Fax: (847) 938-3403. Phone for Linus L. Shen: (847) 937-5983. E-mail: linus.l.shen{at}abbott.com. Phone for Claude G. Lerner: (847) 937-7875. E-mail: claude.lerner{at}abbott.com.

Antimicrobial Agents and Chemotherapy, July 1999, p. 1574-1577, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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