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Journal of Antimicrobial Chemotherapy (2000) 45, 101
© 2000 The British Society for Antimicrobial Chemotherapy

Purification of pneumococcal type II topoisomerases and inhibition by gemifloxacin and other quinolones

Ian Morrissey* and John T. George

GR Micro Ltd, 7–9 William Road, London NW1 3ER, UK

Topoisomerase IV and DNA gyrase were purified from a ciprofloxacin-sensitive Streptococcus pneumoniae strain and from two clinical isolates of S. pneumoniae with high-level resistance to ciprofloxacin by means of a gene cloning method in Escherichia coli. All the quinolones tested (gemifloxacin, trovafloxacin, levofloxacin, ciprofloxacin and grepafloxacin) were able to inhibit topoisomerase IV at lower concentrations than those required for DNA gyrase, suggesting that topoisomerase IV is the primary target in the three pneumococci, in agreement with recently published enzyme data. Gemifloxacin (SB-265805) was found to be the most active agent against topoisomerase IV but, surprisingly, not against DNA gyrase. These findings indicate that the potent in vitro activity of gemifloxacin against S. pneumoniae, including ciprofloxacin-resistant strains, results from a strong affinity for pneumococcal topoisomerase IV.

* Corresponding author. Tel: +44-20-7388-7320; Fax: +44-20-7388-7324; E-mail: i.morrissey{at}grmicro.co.uk


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