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Antimicrobial Agents and Chemotherapy, November 1999, p. 2579-2585, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activities of Fluoroquinolones against Streptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins

Ian Morrissey1,* and John George2

GR Micro Ltd., London NW1 3ER,1 and Department of Biosciences, University of Hertfordshire, Hatfield, Herts AL10 9AB,2 United Kingdom

Received 15 December 1998/Returned for modification 12 February 1999/Accepted 26 April 1999

Streptococcus pneumoniae topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible Streptococcus pneumoniae strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from Escherichia coli. The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with S. pneumoniae, ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in S. pneumoniae.

* Corresponding author. Mailing address: GR Micro Ltd., 7-9 William Rd., London NW1 3ER, United Kingdom. Phone: 44 (0)171 388 7320. Fax: 44 (0)171 399 7324. E-mail: i.morrissey{at}grmicro.co.uk.

Antimicrobial Agents and Chemotherapy, November 1999, p. 2579-2585, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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