High-level Fluoroquinolone-resistant Clinical Isolates of Escherichia Coli Overproduce Multidrug Efflux Protein AcrA

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2000 Nov 18

PMID 11083655

Citations 47

Authors

A Mazzariol

Y Tokue

T M Kanegawa

G Cornaglia

H Nikaido

Affiliations

Soon will be listed here.

Abstract

Immunoblotting with antibody against AcrA, an obligatory component of the AcrAB multidrug efflux system, showed that this protein was overexpressed by >/=170% in 9 of 10 clinical isolates of Esherichia coli with high-level ciprofloxacin resistance (MICs, >/=32 microg/ml) but not in any of the 15 isolates for which the MIC was </=1 microg/ml.

Citing Articles

Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.

Kavanaugh L, Dey D, Shafer W, Conn G Microbiol Mol Biol Rev. 2024; 88(3):e0008923.

PMID: 39235227 PMC: 11426026. DOI: 10.1128/mmbr.00089-23.

Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.

Duffey M, Jumde R, da Costa R, Ropponen H, Blasco B, Piddock L ACS Infect Dis. 2024; 10(5):1458-1482.

PMID: 38661541 PMC: 11091901. DOI: 10.1021/acsinfecdis.4c00091.

A Genetic Locus in Associated with Elevated Vancomycin Resistance and Multiple Antibiotic Reduced Susceptibility.

Johnson W, Gupta S, Maharjan S, Morgenstein R, Nicholson A, McQuiston J Antibiotics (Basel). 2024; 13(1).

PMID: 38247620 PMC: 10812688. DOI: 10.3390/antibiotics13010061.

from Human Wounds: Analysis of Resistance to β-Lactams and Expression of RND Efflux Pumps.

Rihacek M, Kuthanova M, Splichal Z, Adam V, Hrazdilova K, Vesely R Infect Drug Resist. 2023; 16:7365-7375.

PMID: 38050628 PMC: 10693772. DOI: 10.2147/IDR.S435622.

Antimicrobial resistance and mechanisms of epigenetic regulation.

Wang X, Yu D, Chen L Front Cell Infect Microbiol. 2023; 13:1199646.

PMID: 37389209 PMC: 10306973. DOI: 10.3389/fcimb.2023.1199646.

References

Everett M, Jin Y, Ricci V, Piddock L . Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother. 1996; 40(10):2380-6. PMC: 163538. DOI: 10.1128/AAC.40.10.2380. View

Kumagai Y, KATO J, Hoshino K, Akasaka T, Sato K, Ikeda H . Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene. Antimicrob Agents Chemother. 1996; 40(3):710-14. PMC: 163185. DOI: 10.1128/AAC.40.3.710. View

Oethinger M, Kern W, Goldman J, Levy S . Association of organic solvent tolerance and fluoroquinolone resistance in clinical isolates of Escherichia coli. J Antimicrob Chemother. 1998; 41(1):111-4. DOI: 10.1093/jac/41.1.111. View

Oethinger M, Podglajen I, Kern W, Levy S . Overexpression of the marA or soxS regulatory gene in clinical topoisomerase mutants of Escherichia coli. Antimicrob Agents Chemother. 1998; 42(8):2089-94. PMC: 105868. DOI: 10.1128/AAC.42.8.2089. View

Hooper D . Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance. Clin Infect Dis. 1998; 27 Suppl 1:S54-63. DOI: 10.1086/514923. View

Zgurskaya H, Nikaido H . AcrA is a highly asymmetric protein capable of spanning the periplasm. J Mol Biol. 1999; 285(1):409-20. DOI: 10.1006/jmbi.1998.2313. View

Zgurskaya H, Nikaido H . Bypassing the periplasm: reconstitution of the AcrAB multidrug efflux pump of Escherichia coli. Proc Natl Acad Sci U S A. 1999; 96(13):7190-5. PMC: 22048. DOI: 10.1073/pnas.96.13.7190. View

Khodursky A, Zechiedrich E, Cozzarelli N . Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci U S A. 1995; 92(25):11801-5. PMC: 40490. DOI: 10.1073/pnas.92.25.11801. View

Alekshun M, Levy S . Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob Agents Chemother. 1997; 41(10):2067-75. PMC: 164072. DOI: 10.1128/AAC.41.10.2067. View

10.

Renau T, Leger R, Flamme E, Sangalang J, She M, Yen R . Inhibitors of efflux pumps in Pseudomonas aeruginosa potentiate the activity of the fluoroquinolone antibacterial levofloxacin. J Med Chem. 1999; 42(24):4928-31. DOI: 10.1021/jm9904598. View

11.

Oethinger M, Kern W, Jellen-Ritter A, McMurry L, Levy S . Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump. Antimicrob Agents Chemother. 1999; 44(1):10-3. PMC: 89620. DOI: 10.1128/AAC.44.1.10-13.2000. View

12.

George A, Levy S . Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. J Bacteriol. 1983; 155(2):531-40. PMC: 217720. DOI: 10.1128/jb.155.2.531-540.1983. View

13.

Okusu H, Ma D, Nikaido H . AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol. 1996; 178(1):306-8. PMC: 177656. DOI: 10.1128/jb.178.1.306-308.1996. View

14.

Heisig P . Genetic evidence for a role of parC mutations in development of high-level fluoroquinolone resistance in Escherichia coli. Antimicrob Agents Chemother. 1996; 40(4):879-85. PMC: 163223. DOI: 10.1128/AAC.40.4.879. View

15.

Maneewannakul K, Levy S . Identification for mar mutants among quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother. 1996; 40(7):1695-8. PMC: 163397. DOI: 10.1128/AAC.40.7.1695. View

16.

Ma D, Alberti M, Lynch C, Nikaido H, Hearst J . The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals. Mol Microbiol. 1996; 19(1):101-12. DOI: 10.1046/j.1365-2958.1996.357881.x. View

17.

Nikaido H . Multidrug efflux pumps of gram-negative bacteria. J Bacteriol. 1996; 178(20):5853-9. PMC: 178438. DOI: 10.1128/jb.178.20.5853-5859.1996. View

18.

Vila J, Ruiz J, Goni P, De Anta M . Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother. 1996; 40(2):491-3. PMC: 163143. DOI: 10.1128/AAC.40.2.491. View