Characterization of GrlA, GrlB, GyrA, and GyrB Mutations in 116 Unrelated Isolates of Staphylococcus Aureus and Effects of Mutations on Ciprofloxacin MIC

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1998 May 21

PMID 9593159

Citations 57

Authors

F J Schmitz

M E Jones

B Hofmann

B Hansen

S Scheuring

M Luckefahr

A Fluit

J Verhoef

U HADDING

H P Heinz

K Kohrer

Affiliations

Soon will be listed here.

Abstract

One hundred sixteen unrelated clinical isolates of Staphylococcus aureus (70 ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries were studied for the presence of mutations in the grlA, grlB, gyrA, and gyrB gene loci. Two mutations within grlA (located at codons 80 and 84) and two mutations within gyrA (located at codons 84 and 88) were clearly associated with ciprofloxacin resistance, although other mutations detected within the four genes studied may also contribute to decreased susceptibility.

Citing Articles

Integrative genomics would strengthen AMR understanding through ONE health approach.

Liu C, Pandey R Heliyon. 2025; 10(14):e34719.

PMID: 39816336 PMC: 11734142. DOI: 10.1016/j.heliyon.2024.e34719.

Time-Kill Analysis of Canine Skin Pathogens: A Comparison of Pradofloxacin and Marbofloxacin.

Azzariti S, Mead A, Toutain P, Bond R, Pelligand L Antibiotics (Basel). 2023; 12(10).

PMID: 37887249 PMC: 10603860. DOI: 10.3390/antibiotics12101548.

Whole genomic sequencing of Staphylococcus aureus strain RMI-014804 isolated from pulmonary patient sputum via next-generation sequencing technology.

Wisal A, Ullah A, Anwar W, Morel C, Hassan S Genomics Inform. 2023; 21(3):e34.

PMID: 37813630 PMC: 10584650. DOI: 10.5808/gi.23024.

Staph wars: the antibiotic pipeline strikes back.

Douglas E, Laabei M Microbiology (Reading). 2023; 169(9).

PMID: 37656158 PMC: 10569064. DOI: 10.1099/mic.0.001387.

Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic.

Silva K, Sundar G, Khare A Nat Commun. 2023; 14(1):3402.

PMID: 37296157 PMC: 10256781. DOI: 10.1038/s41467-023-38507-4.

References

Margerrison E, Hopewell R, Fisher L . Nucleotide sequence of the Staphylococcus aureus gyrB-gyrA locus encoding the DNA gyrase A and B proteins. J Bacteriol. 1992; 174(5):1596-603. PMC: 206555. DOI: 10.1128/jb.174.5.1596-1603.1992. View

Ng E, Trucksis M, Hooper D . Quinolone resistance mutations in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1996; 40(8):1881-8. PMC: 163434. DOI: 10.1128/AAC.40.8.1881. View

Ferrero L, Cameron B, Crouzet J . Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother. 1995; 39(7):1554-8. PMC: 162780. DOI: 10.1128/AAC.39.7.1554. View

Ferrero L, Cameron B, Manse B, Lagneaux D, Crouzet J, Famechon A . Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. Mol Microbiol. 1994; 13(4):641-53. DOI: 10.1111/j.1365-2958.1994.tb00458.x. View

Yamagishi J, Kojima T, Oyamada Y, Fujimoto K, Hattori H, Nakamura S . Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1996; 40(5):1157-63. PMC: 163283. DOI: 10.1128/AAC.40.5.1157. View

Ito H, Yoshida H, Niga T, Hattori H, Nakamura S . Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob Agents Chemother. 1994; 38(9):2014-23. PMC: 284677. DOI: 10.1128/AAC.38.9.2014. View

Kaatz G, Seo S . Inducible NorA-mediated multidrug resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1995; 39(12):2650-5. PMC: 163006. DOI: 10.1128/AAC.39.12.2650. View

Brockbank S, Barth P . Cloning, sequencing, and expression of the DNA gyrase genes from Staphylococcus aureus. J Bacteriol. 1993; 175(11):3269-77. PMC: 204723. DOI: 10.1128/jb.175.11.3269-3277.1993. View

Takahata M, Yonezawa M, Kurose S, Futakuchi N, Matsubara N, Watanabe Y . Mutations in the gyrA and grlA genes of quinolone-resistant clinical isolates of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1996; 38(3):543-6. DOI: 10.1093/jac/38.3.543. View

10.

Goldstein F, Acar J . Epidemiology of quinolone resistance: Europe and North and South America. Drugs. 1995; 49 Suppl 2:36-42. DOI: 10.2165/00003495-199500492-00007. View

11.

Ng E, Trucksis M, Hooper D . Quinolone resistance mediated by norA: physiologic characterization and relationship to flqB, a quinolone resistance locus on the Staphylococcus aureus chromosome. Antimicrob Agents Chemother. 1994; 38(6):1345-55. PMC: 188209. DOI: 10.1128/AAC.38.6.1345. View

12.

Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M . Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol. 1990; 172(12):6942-9. PMC: 210814. DOI: 10.1128/jb.172.12.6942-6949.1990. View

13.

Hori S, Ohshita Y, Utsui Y, Hiramatsu K . Sequential acquisition of norfloxacin and ofloxacin resistance by methicillin-resistant and -susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 1993; 37(11):2278-84. PMC: 192379. DOI: 10.1128/AAC.37.11.2278. View

14.

Blanche F, Cameron B, Bernard F, Maton L, Manse B, Ferrero L . Differential behaviors of Staphylococcus aureus and Escherichia coli type II DNA topoisomerases. Antimicrob Agents Chemother. 1996; 40(12):2714-20. PMC: 163609. DOI: 10.1128/AAC.40.12.2714. View

15.

Schmitz F, Steiert M, Tichy H, Hofmann B, Verhoef J, Heinz H . Typing of methicillin-resistant Staphylococcus aureus isolates from Düsseldorf by six genotypic methods. J Med Microbiol. 1998; 47(4):341-51. DOI: 10.1099/00222615-47-4-341. View

16.

Goswitz J, Willard K, Fasching C, Peterson L . Detection of gyrA gene mutations associated with ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus: analysis by polymerase chain reaction and automated direct DNA sequencing. Antimicrob Agents Chemother. 1992; 36(5):1166-9. PMC: 188863. DOI: 10.1128/AAC.36.5.1166. View

17.

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; 39(7):1414-8. PMC: 162754. DOI: 10.1128/AAC.39.7.1414. View

18.

Schmitz F, MacKenzie C, Hofmann B, Verhoef J, Heinz H, Kohrer K . Specific information concerning taxonomy, pathogenicity and methicillin resistance of staphylococci obtained by a multiplex PCR. J Med Microbiol. 1997; 46(9):773-8. DOI: 10.1099/00222615-46-9-773. View

19.

Lyon B, Skurray R . Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev. 1987; 51(1):88-134. PMC: 373094. DOI: 10.1128/mr.51.1.88-134.1987. View