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. 1997 Dec;41(12):2766–2769. doi: 10.1128/aac.41.12.2766

Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics.

B Waters 1, J Davies 1
PMCID: PMC164206  PMID: 9420056

Abstract

In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment. It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain. We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development.

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Everett M. J., Jin Y. F., Ricci V., Piddock L. J. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother. 1996 Oct;40(10):2380–2386. doi: 10.1128/aac.40.10.2380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gellert M., Mizuuchi K., O'Dea M. H., Itoh T., Tomizawa J. I. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4772–4776. doi: 10.1073/pnas.74.11.4772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Griggs D. J., Gensberg K., Piddock L. J. Mutations in gyrA gene of quinolone-resistant Salmonella serotypes isolated from humans and animals. Antimicrob Agents Chemother. 1996 Apr;40(4):1009–1013. doi: 10.1128/aac.40.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Guillemin I., Cambau E., Jarlier V. Sequences of conserved region in the A subunit of DNA gyrase from nine species of the genus Mycobacterium: phylogenetic analysis and implication for intrinsic susceptibility to quinolones. Antimicrob Agents Chemother. 1995 Sep;39(9):2145–2149. doi: 10.1128/aac.39.9.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huang W. M. Bacterial diversity based on type II DNA topoisomerase genes. Annu Rev Genet. 1996;30:79–107. doi: 10.1146/annurev.genet.30.1.79. [DOI] [PubMed] [Google Scholar]
  7. Ito H., Yoshida H., Bogaki-Shonai M., Niga T., Hattori H., Nakamura S. Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob Agents Chemother. 1994 Sep;38(9):2014–2023. doi: 10.1128/aac.38.9.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Muñoz R., De La Campa A. G. ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype. Antimicrob Agents Chemother. 1996 Oct;40(10):2252–2257. doi: 10.1128/aac.40.10.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Olsen G. J., Overbeek R., Larsen N., Marsh T. L., McCaughey M. J., Maciukenas M. A., Kuan W. M., Macke T. J., Xing Y., Woese C. R. The Ribosomal Database Project. Nucleic Acids Res. 1992 May 11;20 (Suppl):2199–2200. doi: 10.1093/nar/20.suppl.2199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pan X. S., Ambler J., Mehtar S., Fisher L. M. Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae. Antimicrob Agents Chemother. 1996 Oct;40(10):2321–2326. doi: 10.1128/aac.40.10.2321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Reece R. J., Maxwell A. DNA gyrase: structure and function. Crit Rev Biochem Mol Biol. 1991;26(3-4):335–375. doi: 10.3109/10409239109114072. [DOI] [PubMed] [Google Scholar]
  12. Sreedharan S., Oram M., Jensen B., Peterson L. R., Fisher L. M. DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli. J Bacteriol. 1990 Dec;172(12):7260–7262. doi: 10.1128/jb.172.12.7260-7262.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sugino A., Peebles C. L., Kreuzer K. N., Cozzarelli N. R. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4767–4771. doi: 10.1073/pnas.74.11.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Takenouchi T., Ishii C., Sugawara M., Tokue Y., Ohya S. Incidence of various gyrA mutants in 451 Staphylococcus aureus strains isolated in Japan and their susceptibilities to 10 fluoroquinolones. Antimicrob Agents Chemother. 1995 Jul;39(7):1414–1418. doi: 10.1128/aac.39.7.1414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Takiff H. E., Cimino M., Musso M. C., Weisbrod T., Martinez R., Delgado M. B., Salazar L., Bloom B. R., Jacobs W. R., Jr Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):362–366. doi: 10.1073/pnas.93.1.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Truong Q. C., Nguyen Van J. C., Shlaes D., Gutmann L., Moreau N. J. A novel, double mutation in DNA gyrase A of Escherichia coli conferring resistance to quinolone antibiotics. Antimicrob Agents Chemother. 1997 Jan;41(1):85–90. doi: 10.1128/aac.41.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vila J., Ruiz J., Goñi P., De Anta M. T. Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother. 1996 Feb;40(2):491–493. doi: 10.1128/aac.40.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yoshida H., Bogaki M., Nakamura M., Yamanaka L. M., Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob Agents Chemother. 1991 Aug;35(8):1647–1650. doi: 10.1128/aac.35.8.1647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yoshida H., Kojima T., Yamagishi J., Nakamura S. Quinolone-resistant mutations of the gyrA gene of Escherichia coli. Mol Gen Genet. 1988 Jan;211(1):1–7. doi: 10.1007/BF00338386. [DOI] [PubMed] [Google Scholar]
  20. Zhanel G. G., Karlowsky J. A., Saunders M. H., Davidson R. J., Hoban D. J., Hancock R. E., McLean I., Nicolle L. E. Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones. Antimicrob Agents Chemother. 1995 Feb;39(2):489–495. doi: 10.1128/aac.39.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]

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