Inhibitors of efflux pumps in Pseudomonas aeruginosa potentiate the activity of the fluoroquinolone antibacterial levofloxacin

Journal of Medicinal Chemistry

Volumn 42, Issue 24, 1999, Pages 4928-4931

  Renau, Thomas E ^a   Léger, Roger ^a   Flamme, Eric M ^a   Sangalang, Joan ^a   She, Miles W ^a   Yen, Rose ^a   Gannon, Carla L ^a   Griffith, David ^a   Chamberland, Suzanne ^a   Lomovskaya, Olga ^a   Hecker, Scott J ^a   Lee, Ving J ^a   Ohta, Toshiharu ^b   Nakayama, Kiyoshi ^b  

^a Microcide Pharmaceuticals Inc   (United States)

^b DAIICHI SANKYO CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

LEVOFLOXACIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT;

ANTIBACTERIAL ACTIVITY; DRUG ACTIVITY; DRUG STRUCTURE; LETTER; MINIMUM INHIBITORY CONCENTRATION; PSEUDOMONAS AERUGINOSA;

ANTI-INFECTIVE AGENTS; BACTERIAL OUTER MEMBRANE PROTEINS; CARRIER PROTEINS; DIPEPTIDES; DRUG RESISTANCE, MICROBIAL; DRUG STABILITY; DRUG SYNERGISM; ENDOPEPTIDASES; GENE EXPRESSION; MEMBRANE TRANSPORT PROTEINS; MOLECULAR STRUCTURE; OFLOXACIN; ORNITHINE; PSEUDOMONAS AERUGINOSA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0344717988     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9904598     Document Type: Letter

References (39)

1. (a) Gold, H. S.; Moellering, R. C., Jr. Antimicrobial-drug resistance. N. Engl. J. Med. 1996, 335, 1445-1453.
2. (b) Chu, D. T. W.; Plattner, J. J. New directions in antibacterial research. J. Med. Chem. 1996, 39, 3853-3874.
3. (c) Domagala, J. M.; Sanchez, J. P. New approaches and agents to overcome bacterial resistance. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: New York, 1997; pp 111-120.
4. (d) Perl, T. M. The threat of vancomycin resistance. Am. J. Med. 1999, 106 (5A), 26S-37S.
5. (e) Chopra, I. Research and devlopment of antibacterial agents. Curr. Opin. Microbiol. 1998, 1, 495-501.
6. (a) Coleman, K.; Athalye, M.; Clancey, A.; Davison, M.; Payne, D. J.; Perry, C. R.; Chopra, I. Bacterial resistance mechanisms as therapeutic targets. J. Antimicrob. Chemother. 1994, 33, 1091-1116.
7. (b) Brighty, K. E. Recent developments in antibacterial resistance mechanisms. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: New York, 1993; pp 141-150.
8. (a) Davies, J. Inactivation of antibiotics and the dissemination of resistance genes. Science 1994, 264, 375-381.
9. (b) Spratt, B. G. Resistance to antibiotics mediated by target alterations. Science 1994, 264, 388-393.
10. (a) Lawrence, L. E.; Barrett, J. F. Efflux pumps in bacteria: overview, clinical relevance and potential pharmaceutical target. Exp. Opin. Invest. Drugs 1998, 7, 199-217.
11. (b) Marshall, N. J.; Piddock, L. J. Antibacterial efflux systems. Microbiologia 1997, 13, 285-300.
12. (c) Nikaido, H. Antibiotic resistance caused by gram-negative multidrug efflux pumps. Clin. Infect. Dis. 1998, 27, S32-S41.
13. (d) Lee, V. J.; Lomovskaya, O. Efflux-mediated resistance to antibiotics in bacteria: challenges and opportunities. CLEAR 1998, 1, 39-42.
14. (e) Levy, S. B. Active efflux mechanisms for antimicrobial resistance. Antimicrob. Agents Chemother. 1992, 36, 695-703.
15. Brenwald, N. P.; Gill, M. J.; Wise, R. Prevalence of a putative efflux mechanism among fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 1998, 42, 2032-2035.
16. (a) Travis, J. Reviving the antibiotic miracle? Science 1994, 264, 360-362.
17. (b) Renau, T. E.; Hecker, S. J.; Lee, V. J. Antimicrobial potentiation approaches: targets and inhibitors. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: New York, 1998; pp 121-130.
18. (a) Nelson, M. L.; Park, B. H.; Andrews, J. S.; Georgian, V. A.; Thomas, R. C.; Levy, S. B. Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hydroxy-6-deoxytetracyclines. J. Med. Chem. 1993, 36, 370-377.
19. (b) Nelson, M. L.; Park, B. H.; Levy, S. B. Molecular requirements for the inhibition of the tetracycline antiport protein and the effect of potent inhibitors on the growth of tetracycline-resistant bacteria. J. Med. Chem. 1994, 37, 1355-1361.
20. (c) Hirata, T.; Wakatabe, R.; Nielsen, J.; Satoh, T.; Nihira, S.; Yamaguchi, A. Screening of an inhibitor of the tetracycline efflux pump in a tetracycline-resistant clinical isolate of Staphylococcus aureus 743. Biol. Pharm. Bull. 1998, 21, 678-681.
21. (d) Rothstein, D. M.; McGlynn, M.; Bernan, V.; McGahren, J.; Zaccardi, J.; Cekleniak, N.; Bertrand, K. P. Detection of tetracyclines and efflux pump inhibitors. Antimicrob. Agents Chemother. 1993, 37, 1624-1629.
22. (a) Li, X. Z.; Livermore, D. M.; Nikaido, H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol and norfloxacin. Antimicrob. Agents Chemother. 1994, 38, 1732-1741.
23. (b) Li, X. Z.; Ma, D.; Livermore, D. M.; Nikaido, H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to β-lactam resistance. Antimicrob. Agents Chemother. 1994, 38, 1742-1752.
24. (c) Hancock, R. E. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative Gram-negative bacteria. Clin. Infect. Dis. 1998, 27 (Suppl. 1), S93-S99.
25. (a) Poole, K.; Krebes, K.; McNally, C.; Neshat, S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J. Bacteriol. 1993, 175, 7363-7372.
26. (b) Poole, K.; Gotoh, N.; Tsujimoto, H.; Zhao, Q.; Wada, A.; Yamasaki, T.; Neshat, S.; Yamagishi, J.; Li, X. Z.; Nishino, T. Overexpression of the mexC-mexD-oprJ efflux operon in nfx-B-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol. Microbiol. 1996, 21, 713-724.
27. (c) Koehler, T.; Michea-Hamzehpour, M.; Henze, U.; Gotoh, N.; Curty, L. K.; Pechere, J. C. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol. Microbiol. 1997, 23, 345-354.
28. (d) Mine, T.; Morita, Y.; Kataoka, A.; Mizushima, T.; Tsuchiya, T. Expression in Eschericia coli of a new multidrug efflux pump, MexXY, from Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 1999, 43, 415-417.
29. th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Sept 24-27, 1998, San Diego, CA; Abstract C-120.
30. (b) Lomovskaya, O.; Lee, A.; Hoshino, K.; Mistry, A.; Warren, M. S.; Boyer, E.; Lee, V. J. Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 1999, 43, 1340-1346.
31. (a) Chen, H. Y.; Yuan, M.; Livermore, D. M. Mechanisms of resistance to beta-lactam antibiotics amongst Pseudomonas aeruginosa isolates collected in the UK in 1993. J. Med. Microbiol. 1995, 43, 300-309.
32. (b) Jakics, E. B.; Iyobe, S.; Hirai, K.; Fukuda, H.; Hashimoto, H. Occurrence of the nfxB type mutation in clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 1992, 36, 2562-2565.
33. (c) Fukuda, H.; Hosaka, M.; Iyobe, S.; Gotoh, N.; Nishimo, T.; Hirai, K. nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 1995, 39, 790-792.
34. th ICAAC, Sept 24-27, 1998, San Diego, CA; Abstract C-119.
35. (a) Chamberland, S.; Hecker, S. J.; Lee, V. J.; Trias, J. Efflux pump inhibitors. Int. Appl. WO9633285, 1996.
36. (b) A genotypic description of the strains used in this study can be found in ref 10b.
37. th ICAAC, Sept 26-29, 1999, San Francisco, CA; Abstract F-1264.
38. Prichard, M. N.; Shipman, C., Jr. A three-dimensional model to analyze drug-drug interactions. Antiviral Res. 1990, 14, 181-206.
39. Léger, R.; Yen, R.; She, M. W.; Lee, V. J.; Hecker, S. J. N-linked solid-phase peptide synthesis. Tetrahedron Lett. 1998, 39, 4171-4174.