The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Mechanisms of Action and Resistance of Older and Newer Fluoroquinolones
Abstract
The fluoroquinolones interact with 2 bacterial targets, the related enzymes DNA gyrase and topoisomerase IV, both of which are involved in DNA replication. Quinolones form complexes of these enzymes with DNA, complexes that block movement of the DNA-replication fork and thereby inhibit DNA replication. Many older quinolones differ in their relative activities against gyrase and topoisomerase IV in a bacterial cell, having greater potency against gyrase than against topoisomerase IV in many gram-negative bacteria and greater potency against topoisomerase IV than against gyrase in many gram-positive bacteria. Several newer quinolones appear to have more closely balanced activity against these enzymes. Resistance to fluoroquinolones occurs as a result of mutational amino acid substitutions in the subunits of the more sensitive (or primary-target) enzyme within the cell. If, however, both enzymes are similarly susceptible to a fluoroquinolone, then the level of resistance caused by a primary-target mutation may be low and may be limited by the sensitivity of the secondary target. Fluoroquinolones also differ in the extent to which common bacterial multidrug efflux pumps affect their activity, with some compounds being unaffected by resistance mechanisms because of overexpression of such pumps. Newer fluoroquinolone interaction with dual targets and avoidance of efflux-resistance mechanisms may each contribute to the lower frequencies of selection of resistant mutants in the laboratory.
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Cites
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DNA gyrase, topoisomerase IV, and the 4-quinolones.
Drlica, K., & Zhao, X. (1997) · Microbiology and molecular biology reviews : MMBR · doi:10.1128/.61.3.377-392.1997 · Cited by 1,494
Mechanisms of fluoroquinolone resistance
Hooper, D. C. (1999) · Drug Resistance Updates · doi:10.1054/drup.1998.0068 · Cited by 488
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Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus
Kaatz, G. W., Seo, S. M., & Ruble, C. A. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.5.1086 · Cited by 413
Topoisomerase IV is a target of quinolones in Escherichia coli.
Khodursky, A. B., Zechiedrich, E. L., & Cozzarelli, N. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11801 · Cited by 378
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Miller, W. R., Munita, J. M., & Arias, C. A. (2014) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2014.956092 · Cited by 772
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Grillon, A., Schramm, F., Kleinberg, M., & Jehl, F. (2016) · PLOS ONE · doi:10.1371/journal.pone.0156690 · Cited by 124
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Kumbhari, A., Cheng, T. N. H., Ananthakrishnan, A. N., Kochar, B., Burke, K. E., Shannon, K., Lau, H., Xavier, R. J., & Smillie, C. S. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2024.05.022 · Cited by 54
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Metadata
- Authors
- Hooper, D. C.
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08-01
- Volume
- 31
- Issue
- Supplement_2
- Pages
- S24-S28
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2149410208
- Cited by
- 409
- References
- 22
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- closed
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