Mechanism of Quinolone Action and Resistance
Open accessAbstract
Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone–enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Harboring Qnr-encoding genes promotes the emergence of highly resistant isolates by facilitating selection of mutants with point mutations in genes encoding DNA gyrase and/or topoisomerase IV.
“However, harboring Qnr-encoding genes has been shown to promote the emergence of highly resistant isolates by facilitating the selection of mutants with point mutations in genes encoding the DNA gyrase and/or topoisomerase IV (56)”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DNA Topoisomerases: Structure, Function, and Mechanism
Champoux, J. J. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.369 · Cited by 2,748 · see citing works
DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs
Pommier, Y. G., Leo, E., Zhang, H., & Marchand, C. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.04.012 · Cited by 1,842 · see citing works
DNA gyrase, topoisomerase IV, and the 4-quinolones
Drlica, K., & Zhao, X. (1997) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.61.3.377-392.1997 · Cited by 1,272 · see citing works
Quinolone resistance from a transferable plasmid
Martı́nez-Martı́nez, L., Pascual, Á., & Jacoby, G. A. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07322-4 · Cited by 1,104 · see citing works
Plasmids and the spread of resistance
Carattoli, A. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.02.001 · Cited by 1,032 · see citing works
Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase
Robicsek, A. A., Strahilevitz, J., Jacoby, G. A., Macielag, M. J., Abbanat, D., Park, C. H., Bush, K., & Hooper, D. C. (2005) · Nature Medicine · doi:10.1038/nm1347 · Cited by 1,011 · see citing works
The worldwide emergence of plasmid-mediated quinolone resistance
Robicsek, A. A., Jacoby, G. A., & Hooper, D. C. (2006) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(06)70599-0 · Cited by 965 · see citing works
Mechanisms of Resistance to Quinolones
Jacoby, G. A. (2005) · Clinical Infectious Diseases · doi:10.1086/428052 · Cited by 928 · see citing works
Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat
Strahilevitz, J., Jacoby, G. A., Hooper, D. C., & Robicsek, A. A. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00016-09 · Cited by 926 · see citing works
Type IIA topoisomerase inhibition by a new class of antibacterial agents
Bax, B. D., Chan, P. F., Eggleston, D. S., et al. (2010) · Nature · doi:10.1038/nature09197 · Cited by 863 · see citing works
Nalidixic acid resistance: A second genetic character involved in DNA gyrase activity
Gellert, M. F., Mizuuchi, K., O'Dea, M. H., Itoh, T., & Tomizawa, J.-I. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.11.4772 · Cited by 834 · see citing works
Bacterial Topoisomerase Inhibitors: Quinolone and Pyridone Antibacterial Agents
Mitscher, L. A. (2005) · Chemical Reviews · doi:10.1021/cr030101q · Cited by 788 · see citing works
Sugino, A., Peebles, C. L., Kreuzer, K. N., & Cozzarelli, N. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.11.4767 · Cited by 784 · see citing works
1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents
Lesher, G. Y., Froelich, E. J., Gruett, M. D., et al. (1962) · Journal of Medicinal Chemistry · doi:10.1021/jm01240a021 · Cited by 770 · see citing works
Emerging Mechanisms of Fluoroquinolone Resistance
Hooper, D. C. (2001) · Emerging infectious diseases · doi:10.3201/eid0702.010239 · Cited by 631 · see citing works
Quinolone-Mediated Bacterial Death
Drlica, K., Malik, M., Kerns, R. J., & Zhao, X. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01617-06 · Cited by 569 · see citing works
Self-citationMechanism of plasmid-mediated quinolone resistance
Tran, J. H., & Jacoby, G. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082092899 · Cited by 568 · see citing works
New topoisomerase essential for chromosome segregation in E. coli
Kato, J., Nishimura, Y., Imamura, R., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90172-b · Cited by 567 · see citing works
Efflux pumps as antimicrobial resistance mechanisms
Poole, K. (2007) · Annals of Medicine · doi:10.1080/07853890701195262 · Cited by 561 · see citing works
The quinolones: decades of development and use
Emmerson, A. M. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg208 · Cited by 533 · see citing works
Mechanisms of Action of Antimicrobials: Focus on Fluoroquinolones
Hooper, D. C. (2001) · Clinical Infectious Diseases · doi:10.1086/319370 · Cited by 522 · see citing works
Plasmid-Mediated Quinolone Resistance in Clinical Isolates of Escherichia coli from Shanghai, China
Wang, M., Tran, J. H., Jacoby, G. A., Zhang, Y., Wang, F., & Hooper, D. C. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.7.2242-2248.2003 · Cited by 467 · see citing works
The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing
Deweese, J. E., & Osheroff, N. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn937 · Cited by 466 · see citing works
Self-citationYamane, K., Wachino, J., Suzuki, S., Kimura, K., Shibata, N., Kato, H., Shibayama, K., Konda, T., & Arakawa, Y. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00339-07 · Cited by 466 · see citing works
Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae
Pan, X.-S., Ambler, J. E., Mehtar, S., et al. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.10.2321 · Cited by 441 · see citing works
The Quinolones: Past, Present, and Future
Andriole, V. T. (2005) · Clinical Infectious Diseases · doi:10.1086/428051 · Cited by 428 · see citing works
Levine, C., Hiasa, H., & Marians, K. J. (1998) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(98)00126-2 · Cited by 392 · see citing works
Topoisomerase IV is a target of quinolones in Escherichia coli.
Khodursky, A. B., Zechiedrich, L., & Cozzarelli, N. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11801 · Cited by 379 · see citing works
Quinolones: Action and Resistance Updated
Drlica, K., Hiasa, H., Kerns, R. J., Malik, M., MUSTAEV, A. A., & Zhao, X. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609789630947 · Cited by 377 · see citing works
Self-citationOrigin and evolution of DNA topoisomerases
Forterre, P., Gribaldo, S., Gadelle, D., & Serre, M.-C. (2007) · Biochimie · doi:10.1016/j.biochi.2006.12.009 · Cited by 344 · see citing works
Kreuzer, K. N., & Cozzarelli, N. R. (1979) · Journal of Bacteriology · doi:10.1128/jb.140.2.424-435.1979 · Cited by 337 · see citing works
Roles of Topoisomerases in Maintaining Steady-state DNA Supercoiling in Escherichia coli
Zechiedrich, L., Khodursky, A. B., Bachellier‐Bassi, S., Schneider, R., Chen, D., Lilley, D. M. J., & Cozzarelli, N. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.8103 · Cited by 328 · see citing works
Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance
Wohlkönig, A., Chan, P. F., Fosberry, A. P., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1892 · Cited by 311 · see citing works
Fluoroquinolone prescribing in the United States: 1995 to 2002
Linder, J. A., Huang, E. S., Steinman, M. A., Gonzales, R., & Stafford, R. S. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.09.015 · Cited by 309 · see citing works
Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases
Laponogov, I., Sohi, M. K., Veselkov, D. A., et al. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1604 · Cited by 307 · see citing works
Plasmid-mediated quinolone resistance: an update
Rodríguez-Martínez, J. M., Velasco, C., Pascual, Á., Cano, M. E., Martínez-Martínez, L., Martínez-Martínez, L., & Pascual, Á. (2011) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-010-0120-2 · Cited by 306 · see citing works
Mode of Action of Fluoroquinolones
Hooper, D. C. (1999) · Drugs · doi:10.2165/00003495-199958002-00002 · Cited by 289 · see citing works
Interaction of the Plasmid-Encoded Quinolone Resistance Protein Qnr with Escherichia coli DNA Gyrase
Tran, J. H., Jacoby, G. A., & Hooper, D. C. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.1.118-125.2005 · Cited by 283 · see citing works
oqxAB Encoding a Multidrug Efflux Pump in Human Clinical Isolates of Enterobacteriaceae
Kim, H. B., Wang, M., Park, C. H., Kim, E.-C., Jacoby, G. A., & Hooper, D. C. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01574-08 · Cited by 270 · see citing works
Willmott, C., & Maxwell, A. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.1.126 · Cited by 253 · see citing works
Martinez-Freijo, P., Fluit, A. C., Schmitz, F.-J., et al. (1998) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/42.6.689 · Cited by 245 · see citing works
Pan, X.-S., & Fisher, L. M. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.2.471 · Cited by 237 · see citing works
DNA Gyrase and Topoisomerase IV Are Dual Targets of Clinafloxacin Action in Streptococcus pneumoniae
Pan, X.-S., & Fisher, L. M. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.11.2810 · Cited by 215 · see citing works
Forterre, P., & Gadelle, D. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp032 · Cited by 190 · see citing works
Type II Topoisomerases as Targets for Quinolone Antibacterials Turning Dr. Jekyll into Mr. Hyde
Anderson, V., & Osheroff, N. (2001) · Current Pharmaceutical Design · doi:10.2174/1381612013398013 · Cited by 190 · see citing works
Self-citationA novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases
Thurtle-Schmidt, B. H., Burgin, A. B., Deweese, J. E., Osheroff, N., & Berger, J. M. (2010) · Nature · doi:10.1038/nature08974 · Cited by 183 · see citing works
Self-citationStructural Basis of Gate-DNA Breakage and Resealing by Type II Topoisomerases
Laponogov, I., Pan, X.-S., Veselkov, D. A., McAuley, K. E., Fisher, L. M., & Sanderson, M. R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011338 · Cited by 178 · see citing works
Fluoroquinolone-Gyrase-DNA Complexes
MUSTAEV, A. A., Malik, M., Zhao, X., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.529164 · Cited by 173 · see citing works
Aldred, K. J., McPherson, S. A., Turnbough, C. L., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt124 · Cited by 173 · see citing works
Self-citationThe C-terminal domain of DNA gyrase A adopts a DNA-bending β-pinwheel fold
Corbett, K. D., Shultzaberger, R. K., & Berger, J. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401595101 · Cited by 168 · see citing works
Tran, J. H., Jacoby, G. A., & Hooper, D. C. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.7.3050-3052.2005 · Cited by 167 · see citing works
Anderson, V. R., & Perry, C. M. (2008) · Drugs · doi:10.2165/00003495-200868040-00011 · Cited by 164 · see citing works
Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates
Morgan‐Linnell, S. K., Boyd, L. B., Steffen, D. L., et al. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00665-08 · Cited by 162 · see citing works
Barnard, F. M., & Maxwell, A. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.7.1994-2000.2001 · Cited by 160 · see citing works
Plasmid-Mediated Quinolone Resistance Pump QepA2 in an Escherichia coli Isolate from France
Cattoir, V., Poirel, L., & Nordmann, P. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00638-08 · Cited by 134 · see citing works
DNA topology and topoisomerases
Deweese, J. E., Osheroff, M. A., & Osheroff, N. (2009) · Biochemistry and Molecular Biology Education · doi:10.1002/bmb.20244 · Cited by 129 · see citing works
Self-citationInteraction of plasmid and host quinolone resistance
Martı́nez-Martı́nez, L. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg157 · Cited by 119 · see citing works
Price, L. B., Vogler, A. J., Pearson, T., Busch, J. D., Schupp, J. M., & Keim, P. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.7.2362-2365.2003 · Cited by 118 · see citing works
Fournier, B., Zhao, X., Lu, T., et al. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.8.2160-2165.2000 · Cited by 112 · see citing works
Resistance surveillance studies: a multifaceted problem—the fluoroquinolone example
Dalhoff, A. (2012) · Infection · doi:10.1007/s15010-012-0257-2 · Cited by 111 · see citing works
Topoisomerase IV, alone, unknots DNA in E. coliPreprint
Deibler, R. W., Rahmati, S., & Zechiedrich, L. (2001) · Genes & Development · doi:10.1101/gad.872301 · Cited by 110 · see citing works
Is plasmid-mediated quinolone resistance a clinically significant problem?
Poirel, L., Cattoir, V., & Nordmann, P. (2008) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2007.01930.x · Cited by 100 · see citing works
Aldred, K. J., McPherson, S. A., Wang, P., et al. (2011) · Biochemistry · doi:10.1021/bi2013905 · Cited by 92 · see citing works
Self-citationXiong, X., Bromley, E. H. C., Oelschlaeger, P., Woolfson, D. N., & SPENCER, J. M. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1296 · Cited by 91 · see citing works
Hansen, L. H., S⊘rensen, S. J., Jørgensen, H. S., et al. (2005) · Microbial Drug Resistance · doi:10.1089/mdr.2005.11.378 · Cited by 81 · see citing works
Goldman, J. D., White, D. G., & Levy, S. B. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.5.1266 · Cited by 80 · see citing works
Topoisomerase IV Catalysis and the Mechanism of Quinolone Action
Anderson, V. E., Gootz, T. D., & Osheroff, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17879 · Cited by 75 · see citing works
Self-citationSingh, R., Swick, M. C., Ledesma, K. R., Yang, Z., Hu, M., Zechiedrich, L., & Tam, V. H. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05693-11 · Cited by 75 · see citing works
Plasmid-mediated quinolone resistance – current knowledge and future perspectives
Guan, X., Xue, X., Liu, Y., et al. (2013) · Journal of International Medical Research · doi:10.1177/0300060513475965 · Cited by 71 · see citing works
Mechanisms for Defining Supercoiling Set Point of DNA Gyrase Orthologs
Tretter, E. M., & Berger, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.345678 · Cited by 70 · see citing works
Aldred, K. J., Schwanz, H. A., Li, G., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400592n · Cited by 69 · see citing works
Self-citationThe use of divalent metal ions by type II topoisomerases
Deweese, J. E., & Osheroff, N. (2010) · Metallomics · doi:10.1039/c003759a · Cited by 68 · see citing works
Self-citationPan, X.-S., Yagüe, G., & Fisher, L. M. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.11.3140-3147.2001 · Cited by 68 · see citing works
Pan, X.-S., Gould, K. A., & Fisher, L. M. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00113-09 · Cited by 64 · see citing works
Hiramatsu, K., Igarashi, M., Morimoto, Y., Baba, T., Umekita, M., & Akamatsu, Y. (2012) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2012.02.007 · Cited by 62 · see citing works
Ciprofloxacin affects conformational equilibria of DNA gyrase A in the presence of magnesium ions
Sissi, C., Perdonà, E., Domenici, E., et al. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4838 · Cited by 59 · see citing works
Mechanisms for Defining Supercoiling Set Point of DNA Gyrase Orthologs
Tretter, E. M., & Berger, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.345736 · Cited by 59 · see citing works
Malik, M., Marks, K. R., MUSTAEV, A. A., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00033-11 · Cited by 55 · see citing works
Yagüe, G., Morris, J. E., Pan, X.-S., et al. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.2.413-419.2002 · Cited by 54 · see citing works
Quinolones Inhibit DNA Religation Mediated by Staphylococcus aureus Topoisomerase IV
Anderson, V. E., Zaniewski, R. P., Kaczmarek, F. S., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35927 · Cited by 51 · see citing works
Tran, T. P., Ellsworth, E. L., Sanchez, J. P., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.12.005 · Cited by 51 · see citing works
The 4‐Quinolone Antibiotics: Past, Present, and Future
Stein, G. E. (1988) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1988.tb04088.x · Cited by 49 · see citing works
Use of Gyrase Resistance Mutants To Guide Selection of 8-Methoxy-Quinazoline-2,4-Diones
German, N. A., Malik, M., Rosen, J. D., et al. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00330-08 · Cited by 44 · see citing works
A Review of Levofloxacin for the Treatment of Bacterial Infections
Noel, G. J. (2009) · Clinical Medicine Therapeutics · doi:10.4137/cmt.s28 · Cited by 40 · see citing works
Guillard, T., Cambau, E., Chau, F., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01489-13 · Cited by 39 · see citing works
Hiasa, H. (2002) · Biochemistry · doi:10.1021/bi026352v · Cited by 36 · see citing works
Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV
Pitts, S. L., Liou, G. F., Mitchenall, L. A., Burgin, A. B., Maxwell, A., Neuman, K. C., & Osheroff, N. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr018 · Cited by 35 · see citing works
Self-citationLi, Z., Deguchi, T., Yasuda, M., et al. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.12.3293 · Cited by 34 · see citing works
Gentry, A. C., & Osheroff, N. (2013) · Encyclopedia of Biological Chemistry · doi:10.1016/b978-0-12-378630-2.00246-2 · Cited by 34 · see citing works
Self-citationComparison of In Vitro Activities of Fluoroquinolone-Like 2,4- and 1,3-Diones
Oppegard, L. M., Streck, K. R., Rosen, J. D., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00190-10 · Cited by 31 · see citing works
Anderson, V. E., Zaniewski, R. P., Kaczmarek, F. S., et al. (2000) · Biochemistry · doi:10.1021/bi992302n · Cited by 27 · see citing works
Aedo, S. J., & Tse‐Dinh, Y. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01182-12 · Cited by 26 · see citing works
Pfeiffer, E. S., & Hiasa, H. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00362-07 · Cited by 10 · see citing works
A novel family (QnrAS) of plasmid-mediated quinolone resistance determinant
Sun, H. I., Jeong, D. U., Lee, J. H., et al. (2010) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2010.08.009 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Lahey Clinic. qnr Numbering and Sequence (Jacoby G. A., Ed.) http://www.lahey.org/qnrstudies/ (accessed January 9, 2014).
Cited by
Sorted by citations
Mechanisms of Antibiotic Resistance
Munita, J. M., & Arias, C. A. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0016-2015 · Cited by 2,782 · see citing works
Mechanisms of antibiotic resistance
Munita, J. M., & Arias, C. A. (2016) · Virulence Mechanisms of Bacterial Pathogens · doi:10.1128/9781555819286.ch17 · Cited by 421 · see citing works
Menz, B. D., Charani, E., Gordon, D. L., Leather, A. J., Moonesinghe, S. R., & Phillips, C. J. (2021) · Infection and Drug Resistance · doi:10.2147/idr.s319780 · Cited by 118 · see citing works
Carballo-Pacheco, M., Nicholson, M. D., Lilja, E. E., Allen, R. J., & Waclaw, B. (2020) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1007930 · Cited by 18 · see citing works
- Authors
- Aldred, K. J., Kerns, R. J., & Osheroff, N.
- Affiliations
- Vanderbilt University (US)
- University of Iowa (US)
- Corresponding author
- Osheroff, Neil
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-02-27
- Volume
- 53
- Issue
- 10
- Pages
- 1565-1574
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC3985860
- OpenAlex
- W2031223726
- Cited by
- 1,282
- References
- 94
- Citations by year
- 2026: 106 · 2025: 125 · 2024: 129 · 2023: 132 · 2022: 112 · 2021: 130 · 2020: 129 · 2019: 123 · 2018: 110 · 2017: 89 · 2016: 52 · 2015: 29 · 2014: 14 · 2013: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biochemistry (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI87671, CA09582, GM033944)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- quinolones, antibiotic resistance, gyrase, topoisomerase IV, plasmid-mediated resistance, porin, efflux pumps, enzyme mutations, drug design
- MeSH terms
- Animals, Anti-Bacterial Agents, Bacteria, Bacterial Infections, Bacterial Proteins, Humans, Quinolones, Drug Resistance, Bacterial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
