title: Purification of pneumococcal type II topoisomerases and inhibition by gemifloxacin and other quinolones.
abstract: 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.
authors.affiliation: GR Micro Ltd, 7-9 William Road, London NW1 3ER, UK. i.morrissey@grmicro.co.uk
authors.forename: I
authors.initials: I
authors.lastname: Morrissey
authors.forename: J T
authors.initials: JT
authors.lastname: George
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D009287:Naphthyridines / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D009287:Naphthyridines; D059005:Topoisomerase II Inhibitors; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II; D000077735:Gemifloxacin