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. 1996 Jan;178(1):306–308. doi: 10.1128/jb.178.1.306-308.1996

AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants.

H Okusu 1, D Ma 1, H Nikaido 1
PMCID: PMC177656  PMID: 8550435

Abstract

Multiple-antibiotic-resistance (Mar) mutants of Escherichia coli are resistant to a wide variety of antibiotics, and increased active efflux is known to be responsible for the resistance to some drugs. The identity of the efflux system, however, has remained unknown. By constructing an isogenic set of E. coli K-12 strains, we showed that the marR1 mutation was incapable of increasing the resistance level in the absence of the AcrAB efflux system. This experiment identified the AcrAB system as the major pump responsible for making the Mar mutants resistant to many agents, including tetracycline, chloramphenicol, ampicillin, nalidixic acid, and rifampin.

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Selected References

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  1. Cohen S. P., Hächler H., Levy S. B. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli. J Bacteriol. 1993 Mar;175(5):1484–1492. doi: 10.1128/jb.175.5.1484-1492.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cohen S. P., McMurry L. M., Levy S. B. marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli. J Bacteriol. 1988 Dec;170(12):5416–5422. doi: 10.1128/jb.170.12.5416-5422.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dinh T., Paulsen I. T., Saier M. H., Jr A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria. J Bacteriol. 1994 Jul;176(13):3825–3831. doi: 10.1128/jb.176.13.3825-3831.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. George A. M., Levy S. B. Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. J Bacteriol. 1983 Aug;155(2):531–540. doi: 10.1128/jb.155.2.531-540.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. George A. M., Levy S. B. Gene in the major cotransduction gap of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline and other antibiotics. J Bacteriol. 1983 Aug;155(2):541–548. doi: 10.1128/jb.155.2.541-548.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenberg J. T., Chou J. H., Monach P. A., Demple B. Activation of oxidative stress genes by mutations at the soxQ/cfxB/marA locus of Escherichia coli. J Bacteriol. 1991 Jul;173(14):4433–4439. doi: 10.1128/jb.173.14.4433-4439.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hächler H., Cohen S. P., Levy S. B. marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli. J Bacteriol. 1991 Sep;173(17):5532–5538. doi: 10.1128/jb.173.17.5532-5538.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lewis K. Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem Sci. 1994 Mar;19(3):119–123. doi: 10.1016/0968-0004(94)90204-6. [DOI] [PubMed] [Google Scholar]
  9. Li X. Z., Livermore D. M., Nikaido H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. Antimicrob Agents Chemother. 1994 Aug;38(8):1732–1741. doi: 10.1128/aac.38.8.1732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Li X. Z., Ma D., Livermore D. M., Nikaido H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta-lactam resistance. Antimicrob Agents Chemother. 1994 Aug;38(8):1742–1752. doi: 10.1128/aac.38.8.1742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lomovskaya O., Lewis K. Emr, an Escherichia coli locus for multidrug resistance. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8938–8942. doi: 10.1073/pnas.89.19.8938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ma D., Cook D. N., Alberti M., Pon N. G., Nikaido H., Hearst J. E. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol. 1995 Apr;16(1):45–55. doi: 10.1111/j.1365-2958.1995.tb02390.x. [DOI] [PubMed] [Google Scholar]
  13. Ma D., Cook D. N., Alberti M., Pon N. G., Nikaido H., Hearst J. E. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J Bacteriol. 1993 Oct;175(19):6299–6313. doi: 10.1128/jb.175.19.6299-6313.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ma D., Cook D. N., Hearst J. E., Nikaido H. Efflux pumps and drug resistance in gram-negative bacteria. Trends Microbiol. 1994 Dec;2(12):489–493. doi: 10.1016/0966-842x(94)90654-8. [DOI] [PubMed] [Google Scholar]
  15. Mizuno T., Chou M. Y., Inouye M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci U S A. 1984 Apr;81(7):1966–1970. doi: 10.1073/pnas.81.7.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nikaido H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994 Apr 15;264(5157):382–388. doi: 10.1126/science.8153625. [DOI] [PubMed] [Google Scholar]
  17. Poole K., Krebes K., McNally C., Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363–7372. doi: 10.1128/jb.175.22.7363-7372.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Saier M. H., Jr, Tam R., Reizer A., Reizer J. Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport. Mol Microbiol. 1994 Mar;11(5):841–847. doi: 10.1111/j.1365-2958.1994.tb00362.x. [DOI] [PubMed] [Google Scholar]
  19. Seoane A. S., Levy S. B. Identification of new genes regulated by the marRAB operon in Escherichia coli. J Bacteriol. 1995 Feb;177(3):530–535. doi: 10.1128/jb.177.3.530-535.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sulavik M. C., Gambino L. F., Miller P. F. Analysis of the genetic requirements for inducible multiple-antibiotic resistance associated with the mar locus in Escherichia coli. J Bacteriol. 1994 Dec;176(24):7754–7756. doi: 10.1128/jb.176.24.7754-7756.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

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