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. 1996 Jul;40(7):1695–1698. doi: 10.1128/aac.40.7.1695

Identification for mar mutants among quinolone-resistant clinical isolates of Escherichia coli.

K Maneewannakul 1, S B Levy 1
PMCID: PMC163397  PMID: 8807064

Abstract

Quinolone-resistant clinical Escherichia coli isolates were examined for mutations in the marRAB operon of the multiple antibiotic resistance (mar) locus. Among 23 strains evaluated, 8 were chosen for further study: 3 that showed relatively high levels of uninduced, i.e., constitutive, expression of the operon and 5 with variable responses to induction by salicylate or tetracyclines. The marR genes, specifying the repressor of the operon, cloned from the three strains constitutively expressing the operon did not reduce the level of expression of beta-galactosidase from a marO::lacZ transcriptional fusion and were therefore mutant; however, marR genes cloned from the five other clinical strains repressed LacZ expression and were wild type. All three mutant marR genes contained more than one mutation: a deletion and a point mutation. Inactivation of the mar locus in the three known marR mutant strains with a kanamycin resistance cassette introduced by homologous recombination reduced resistance to quinolones and multiple antibiotics. These findings indicate that mar operon mutations exist in quinolone-resistant clinical E. coli isolates and contribute to quinolone and multidrug resistance.

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Selected References

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  1. Aguiar J. M., Chacon J., Canton R., Baquero F. The emergence of highly fluoroquinolone-resistant Escherichia coli in community-acquired urinary tract infections. J Antimicrob Chemother. 1992 Mar;29(3):349–350. doi: 10.1093/jac/29.3.349. [DOI] [PubMed] [Google Scholar]
  2. Aoyama H., Sato K., Kato T., Hirai K., Mitsuhashi S. Norfloxacin resistance in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother. 1987 Oct;31(10):1640–1641. doi: 10.1128/aac.31.10.1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ariza R. R., Cohen S. P., Bachhawat N., Levy S. B., Demple B. Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli. J Bacteriol. 1994 Jan;176(1):143–148. doi: 10.1128/jb.176.1.143-148.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barry A. L., Fuchs P. C., Pfaller M. A., Allen S. D., Gerlach E. H. Prevalence of fluoroquinolone-resistant bacterial isolates in four medical centers during the first quarter of 1990. Eur J Clin Microbiol Infect Dis. 1990 Dec;9(12):906–908. doi: 10.1007/BF01967511. [DOI] [PubMed] [Google Scholar]
  5. Beji A., Izard D., Gavini F., Leclerc H., Leseine-Delstanche M., Krembel J. A rapid chemical procedure for isolation and purification of chromosomal DNA from gram-negative bacilli. Anal Biochem. 1987 Apr;162(1):18–23. doi: 10.1016/0003-2697(87)90005-4. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cohen S. P., Levy S. B., Foulds J., Rosner J. L. Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway. J Bacteriol. 1993 Dec;175(24):7856–7862. doi: 10.1128/jb.175.24.7856-7862.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cohen S. P., McMurry L. M., Hooper D. C., Wolfson J. S., Levy S. B. Cross-resistance to fluoroquinolones in multiple-antibiotic-resistant (Mar) Escherichia coli selected by tetracycline or chloramphenicol: decreased drug accumulation associated with membrane changes in addition to OmpF reduction. Antimicrob Agents Chemother. 1989 Aug;33(8):1318–1325. doi: 10.1128/aac.33.8.1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Cohen S. P., Yan W., Levy S. B. A multidrug resistance regulatory chromosomal locus is widespread among enteric bacteria. J Infect Dis. 1993 Aug;168(2):484–488. doi: 10.1093/infdis/168.2.484. [DOI] [PubMed] [Google Scholar]
  11. Cometta A., Calandra T., Bille J., Glauser M. P. Escherichia coli resistant to fluoroquinolones in patients with cancer and neutropenia. N Engl J Med. 1994 Apr 28;330(17):1240–1241. doi: 10.1056/NEJM199404283301717. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Goldman J. D., White D. G., Levy S. B. Multiple antibiotic resistance (mar) locus protects Escherichia coli from rapid cell killing by fluoroquinolones. Antimicrob Agents Chemother. 1996 May;40(5):1266–1269. doi: 10.1128/aac.40.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hamilton C. M., Aldea M., Washburn B. K., Babitzke P., Kushner S. R. New method for generating deletions and gene replacements in Escherichia coli. J Bacteriol. 1989 Sep;171(9):4617–4622. doi: 10.1128/jb.171.9.4617-4622.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Kern W. V., Andriof E., Oethinger M., Kern P., Hacker J., Marre R. Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrob Agents Chemother. 1994 Apr;38(4):681–687. doi: 10.1128/aac.38.4.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maneewannakul S., Maneewannakul K., Ippen-Ihler K. The pKSM710 vector cassette provides tightly regulated lac and T7lac promoters and strategies for manipulating N-terminal protein sequences. Plasmid. 1994 May;31(3):300–307. doi: 10.1006/plas.1994.1032. [DOI] [PubMed] [Google Scholar]
  19. Martin R. G., Rosner J. L. Binding of purified multiple antibiotic-resistance repressor protein (MarR) to mar operator sequences. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5456–5460. doi: 10.1073/pnas.92.12.5456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakamura S., Nakamura M., Kojima T., Yoshida H. gyrA and gyrB mutations in quinolone-resistant strains of Escherichia coli. Antimicrob Agents Chemother. 1989 Feb;33(2):254–255. doi: 10.1128/aac.33.2.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neu H. C. The crisis in antibiotic resistance. Science. 1992 Aug 21;257(5073):1064–1073. doi: 10.1126/science.257.5073.1064. [DOI] [PubMed] [Google Scholar]
  22. Pérez-Trallero E., Urbieta M., Jimenez D., García-Arenzana J. M., Cilla G. Ten-year survey of quinolone resistance in Escherichia coli causing urinary tract infections. Eur J Clin Microbiol Infect Dis. 1993 May;12(5):349–351. doi: 10.1007/BF01964432. [DOI] [PubMed] [Google Scholar]
  23. Seoane A. S., Levy S. B. Characterization of MarR, the repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli. J Bacteriol. 1995 Jun;177(12):3414–3419. doi: 10.1128/jb.177.12.3414-3419.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wolfson J. S., Hooper D. C. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985 Oct;28(4):581–586. doi: 10.1128/aac.28.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]

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