Shiou-Ling Lu

1. Shiou-Ling Lu

2. Quinolone • Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. • Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. • Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. Gram negative bacteria Quinolone Resistant DNA gyrase topoisomerase IV

3. The plasmid-quinolone resistance gene, qnr. and found it in an integron-like environment upstream from qacE1 and sulI.

4. The gene product Qnr was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17. Qnr had pentapeptide repeat domains of 11 and 28 tandem copies.

5. Supercoild DNA + + + + + + DNA gyrase - + + + + + Ciprofloxacin - - + + + + Qnr - - - 2 mM 1mM - Ciprofloxacin Quinolone Qnr DNA gyrase

6. Qnr Ciprofloxacin Quinolone Qnr DNA gyrase

7. Ciprofloxacin vs. Qnr Qnr : 2 mM Ciprofloxacin 0.75 mM 1.5 mM 3 mM 6 mM Ciprofloxacin Quinolone Qnr DNA gyrase v v v

8. Gyrase 0.62 nM 0.31 nM 0.93 nM Qnr Qnr Qnr Qnr DNA gyrase

9. Quinolone Qnr DNA gyrase topoisomerase IV

10. Resistant Gram negative bacteria Quinolone Qnr DNA gyrase topoisomerase IV