Vol.52 No.7 July 2004
Research on quinolones and efflux pump inhibitors in the post-genomic era
New Product Research Laboratories I, Daiichi Pharmaceutical, Co. Ltd.,
1-16-13 Kitakasai, Edogawa-ku, Tokyo, Japan
Abstract
Complete genome sequences of major pathogenic bacteria have been disclosed and available in the public domain for a number of years now, so we can consider ourselves in the post-genomic era. Bacterial genome information has been widely used in research to support the search for new antibacterial agents by validating new targets for antibacterial agents, by analysing the distribution of these targets among species and by surveying trends in the emergence of resistance mutants. Moreover, we can utilize information taken from bacterial genomes to analyze drug-target interactions based on structural details of the target protein deduced from its gene sequence and associated in silico screening for potential inhibitors against the target protein. In our research efforts on quinolones and efflux pump inhibitors, we have used genome information to assess the target distribution, to analyze trends in resistance development and to estimate the effect of target inhibition. Recently, protein crystallization technology has improved greatly, even for membrane-associated proteins, and therefore a structural biological approach may possibly assist in the discovery of new lead compounds that inhibit proteins which were impossible to study in the past.
Key word
post-genome, quinolone resistance, efflux pump, Pseudomonas aeruginosa
Received
May 7, 2004
Accepted
June 15, 2004
Jpn. J. Chemother. 52 (7): 355-360, 2004
