• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jbacterPermissionsJournals.ASM.orgJournalJB ArticleJournal InfoAuthorsReviewers
J Bacteriol. Jan 1994; 176(1): 143–148.
PMCID: PMC205025

Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli.

Abstract

Resistance to multiple antibiotics and certain oxidative stress compounds was conferred by three independently selected mutations (marR1, soxQ1, and cfxB1) that mapped to 34 min on the Escherichia coli chromosome. Mutations at this locus can activate the marRAB operon, in which marR encodes a putative repressor of mar transcription and marA encodes a putative transcriptional activator of defense genes against antibiotics and oxidants. Overexpression of the wild-type MarR protein reversed the phenotypes (antibiotic resistance and increased antioxidant enzyme synthesis) of all three mutants. DNA sequence analysis showed that, like marR1, the other two mutations were alterations of marR: a 285-bp deletion in cfxB1 and a GC-->AT transition at codon 70 (Ala-->Thr) in soxQ1. All three mutations cause increased amounts of mar-specific RNA, which supports the hypothesis that MarR has a repressor function in the expression of the marRAB operon. The level of mar RNA was further induced by tetracycline in both the marR1 and soxQ1 strains but not in the cfxB1 deletion mutant. In the cfxB1 strain, the level of expression of a truncated RNA, with or without tetracycline exposure, was the same as the fully induced level in the other two mutants. Overproduction of MarR in the cfxB1 strain repressed the transcription of the truncated RNA and restored transcriptional inducibility by tetracycline. Thus, induction of the marRAB operon results from the relief of the repression exerted by MarR. The marRAB operon evidently activates both antibiotic resistance and oxidative stress genes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Amábile-Cuevas CF, Demple B. Molecular characterization of the soxRS genes of Escherichia coli: two genes control a superoxide stress regulon. Nucleic Acids Res. 1991 Aug 25;19(16):4479–4484. [PMC free article] [PubMed]
  • Andersen J, Delihas N. micF RNA binds to the 5' end of ompF mRNA and to a protein from Escherichia coli. Biochemistry. 1990 Oct 2;29(39):9249–9256. [PubMed]
  • Beauchamp C, Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971 Nov;44(1):276–287. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Chou JH, Greenberg JT, Demple B. Posttranscriptional repression of Escherichia coli OmpF protein in response to redox stress: positive control of the micF antisense RNA by the soxRS locus. J Bacteriol. 1993 Feb;175(4):1026–1031. [PMC free article] [PubMed]
  • Cohen SP, Hächler H, Levy SB. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli. J Bacteriol. 1993 Mar;175(5):1484–1492. [PMC free article] [PubMed]
  • Cohen SP, Levy SB, Foulds J, Rosner JL. 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. [PMC free article] [PubMed]
  • Cohen SP, McMurry LM, Levy SB. 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. [PMC free article] [PubMed]
  • Cunningham RP, Saporito SM, Spitzer SG, Weiss B. Endonuclease IV (nfo) mutant of Escherichia coli. J Bacteriol. 1986 Dec;168(3):1120–1127. [PMC free article] [PubMed]
  • Demple B. Regulation of bacterial oxidative stress genes. Annu Rev Genet. 1991;25:315–337. [PubMed]
  • Emory SA, Belasco JG. The ompA 5' untranslated RNA segment functions in Escherichia coli as a growth-rate-regulated mRNA stabilizer whose activity is unrelated to translational efficiency. J Bacteriol. 1990 Aug;172(8):4472–4481. [PMC free article] [PubMed]
  • Gambino L, Gracheck SJ, Miller PF. Overexpression of the MarA positive regulator is sufficient to confer multiple antibiotic resistance in Escherichia coli. J Bacteriol. 1993 May;175(10):2888–2894. [PMC free article] [PubMed]
  • George AM, Levy SB. 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. [PMC free article] [PubMed]
  • Greenberg JT, Chou JH, Monach PA, 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. [PMC free article] [PubMed]
  • Greenberg JT, Monach P, Chou JH, Josephy PD, Demple B. Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6181–6185. [PMC free article] [PubMed]
  • Hächler H, Cohen SP, Levy SB. marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli. J Bacteriol. 1991 Sep;173(17):5532–5538. [PMC free article] [PubMed]
  • Hooper DC, Wolfson JS, Souza KS, Ng EY, McHugh GL, Swartz MN. Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation. Antimicrob Agents Chemother. 1989 Mar;33(3):283–290. [PMC free article] [PubMed]
  • Kao SM, Hassan HM. Biochemical characterization of a paraquat-tolerant mutant of Escherichia coli. J Biol Chem. 1985 Sep 5;260(19):10478–10481. [PubMed]
  • Kogoma T, Farr SB, Joyce KM, Natvig DO. Isolation of gene fusions (soi::lacZ) inducible by oxidative stress in Escherichia coli. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4799–4803. [PMC free article] [PubMed]
  • Liochev SI, Fridovich I. Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5892–5896. [PMC free article] [PubMed]
  • Mizuno T, Chou MY, 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. [PMC free article] [PubMed]
  • Nunoshiba T, Hidalgo E, Amábile Cuevas CF, Demple B. Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene. J Bacteriol. 1992 Oct;174(19):6054–6060. [PMC free article] [PubMed]
  • Skarstad K, Thöny B, Hwang DS, Kornberg A. A novel binding protein of the origin of the Escherichia coli chromosome. J Biol Chem. 1993 Mar 15;268(8):5365–5370. [PubMed]
  • White S, Tuttle FE, Blankenhorn D, Dosch DC, Slonczewski JL. pH dependence and gene structure of inaA in Escherichia coli. J Bacteriol. 1992 Mar;174(5):1537–1543. [PMC free article] [PubMed]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...