101-106 Paper 13 Suppl. A

The quinolones inhibit the essential bacterial enzymes DNA gyrase and topoisomerase IV, which alter DNA topology after inserting a double-stranded break. DNA gyrase exists as an A2B2 tetramer, encoded by the gyrA and gyrB genes, and catalyses negative DNA supercoiling. Topoisomerase IV exists as a C2E2 tetramer encoded by the parC and parE genes, and is involved in chromosome partitioning. Previous studies have shown that the quinolones are stronger inhibitors of pneumococcal topoisomerase IV than of pneumococcal DNA gyrase. Furthermore, for Streptococcus pneumoniae the MICs of quinolones correlate well with the topoisomerase IV IC50 but not so well with the DNA gyrase IC50. 4 Hence, topoisomerase IV appears to be the most likely primary target for quinolones in S. pneumoniae. Gemifloxacin is a novel quinolone derivative with potent in vitro activity, particularly against S. pneumoniae. It is active against ciprofloxacinand trovafloxacin-resistant pneumococci. This study was carried out to investigate the molecular basis of the enhanced anti-pneumococcal activity of gemifloxacin compared with other quinolones. Materials and methods