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PMID: 8521301 Published · ppublish English Journal Article

The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds.

Molecular medicine (Cambridge, Mass.) ·Vol. 1 ·No. 4 ·1995-05-00 ·Pages 436-46

Sulavik MC, Gambino LF, Miller PF

Abstract

The marR gene of Escherichia coli encodes a repressor of the marRAB operon, a regulatory locus controlling multiple antibiotic resistance in this organism. Inactivation of marR results in increased expression of marA, which acts at several target genes in the cell leading to reduced antibiotic accumulation. Exposure of E. coli to sodium salicylate (SAL) induces marRAB operon transcription and antibiotic resistance. The mechanism by which SAL antagonizes MarR repressor activity is unclear. Recombinant plasmid libraries were introduced into a reporter strain designed to identify cloned genes encoding MarR repressor activity. Computer analysis of sequence databases was also used to search for proteins related to MarR. A second E. coli gene, MprA, that exhibits MarR repressor activity was identified. Subsequent database searching revealed a family of 10 proteins from a variety of bacteria that share significant amino acid sequence similarity to MarR and MprA. At least four of these proteins are transcriptional repressors whose activity is antagonized by SAL or by phenolic agents structurally related to SAL. The MarR family is identified as a group of regulatory factors whose activity is modulated in response to environmental signals in the form of phenolic compounds. Many of these agents are plant derived. Some of the MarR homologs appear more likely to control systems expressed in animal hosts, suggesting that phenolic sensing by bacteria is important in a variety of environments and in the regulation of numerous processes.

MeSH Terms
Amino Acid Sequence Bacterial Proteins/genetics,metabolism Base Sequence Drug Resistance, Microbial/genetics Drug Resistance, Multiple/genetics Escherichia coli/genetics,metabolism Escherichia coli Proteins Gene Expression Regulation, Bacterial Gene Library Molecular Sequence Data Operon/genetics Phenols/metabolism Repressor Proteins/genetics,metabolism Sequence Alignment
Chemicals
Bacterial Proteins Escherichia coli Proteins MarR protein, E coli Phenols Repressor Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sulavik M C
Therapeutics Department, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Gambino L F
Miller P F
References (42)
42 references, click to expand
  1. Emr, an Escherichia coli locus for multidrug resistance.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8938-42 PMID: 1409590
  2. pecS: a locus controlling pectinase, cellulase and blue pigment production in Erwinia chrysanthemi.
    Mol Microbiol. 1994 Mar;11(6):1127-39 PMID: 8022282
  3. petR, located upstream of the fbcFBC operon encoding the cytochrome bc1 complex, is homologous to bacterial response regulators and necessary for photosynthetic and respiratory growth of Rhodobacter capsulatus.
    Mol Microbiol. 1992 Jun;6(12):1645-54 PMID: 1323023
  4. 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):6181-5 PMID: 1696718
  5. An E. coli promoter induced by the cessation of growth.
    Mol Microbiol. 1987 Sep;1(2):195-201 PMID: 2835580
  6. Improved tools for biological sequence comparison.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 PMID: 3162770
  7. Molecular cloning, expression, and analysis of the genes of the homoprotocatechuate catabolic pathway of Escherichia coli C.
    J Bacteriol. 1988 Nov;170(11):5317-24 PMID: 3053656
  8. 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):531-40 PMID: 6348022
  9. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli.
    J Bacteriol. 1993 Mar;175(5):1484-92 PMID: 8383113
  10. Dual regulation of inaA by the multiple antibiotic resistance (mar) and superoxide (soxRS) stress response systems of Escherichia coli.
    J Bacteriol. 1994 Oct;176(20):6262-9 PMID: 7928997
  11. 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):541-8 PMID: 6307967
  12. Nutrition of the host and natural resistance to infection. V. An improved assay employing genetic markers in the double strain inoculation test.
    J Exp Med. 1956 Feb 1;103(2):207-23 PMID: 13286428
  13. Overexpression of the MarA positive regulator is sufficient to confer multiple antibiotic resistance in Escherichia coli.
    J Bacteriol. 1993 May;175(10):2888-94 PMID: 8491710
  14. Horizontal gene transfer of the Escherichia coli pap and prs pili operons as a mechanism for the development of tissue-specific adhesive properties.
    Mol Microbiol. 1992 Aug;6(16):2225-42 PMID: 1357526
  15. The Escherichia coli C homoprotocatechuate degradative operon: hpc gene order, direction of transcription and control of expression.
    Mol Gen Genet. 1993 Feb;237(1-2):241-50 PMID: 8384293
  16. Strategies in pathogenesis: mechanistic specificity in the detection of generic signals.
    Mol Microbiol. 1993 Mar;7(5):637-45 PMID: 8469110
  17. The terminus region of the Escherichia coli chromosome contains two separate loci that exhibit polar inhibition of replication.
    Proc Natl Acad Sci U S A. 1987 Apr;84(7):1754-8 PMID: 3550796
  18. A gene encoding a tyrosine tRNA synthetase is located near sacS in Bacillus subtilis.
    DNA Seq. 1991;1(4):251-61 PMID: 1806041
  19. Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli.
    J Bacteriol. 1994 Jan;176(1):143-8 PMID: 8282690
  20. Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein.
    Antimicrob Agents Chemother. 1992 Oct;36(10):2280-5 PMID: 1280056
  21. Analysis of the genetic requirements for inducible multiple-antibiotic resistance associated with the mar locus in Escherichia coli.
    J Bacteriol. 1994 Dec;176(24):7754-6 PMID: 8002604
  22. The physical map of the whole E. coli chromosome: application of a new strategy for rapid analysis and sorting of a large genomic library.
    Cell. 1987 Jul 31;50(3):495-508 PMID: 3038334
  23. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  24. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system.
    Gene. 1977;2(2):95-113 PMID: 344137
  25. Cloning and sequencing of the gene which encodes the highly inducible acetamidase of Mycobacterium smegmatis.
    J Gen Microbiol. 1993 Mar;139(3):575-83 PMID: 8473863
  26. A multidrug resistance regulatory chromosomal locus is widespread among enteric bacteria.
    J Infect Dis. 1993 Aug;168(2):484-8 PMID: 8335992
  27. Active efflux of chloramphenicol in susceptible Escherichia coli strains and in multiple-antibiotic-resistant (Mar) mutants.
    Antimicrob Agents Chemother. 1994 Mar;38(3):542-6 PMID: 8203852
  28. Nucleotide sequence of the Escherichia coli regulatory gene mprA and construction and characterization of mprA-deficient mutants.
    J Bacteriol. 1991 Jun;173(12):3924-9 PMID: 1840583
  29. Nonheritable resistance to chloramphenicol and other antibiotics induced by salicylates and other chemotactic repellents in Escherichia coli K-12.
    Proc Natl Acad Sci U S A. 1985 Dec;82(24):8771-4 PMID: 3909154
  30. mprA, an Escherichia coli gene that reduces growth-phase-dependent synthesis of microcins B17 and C7 and blocks osmoinduction of proU when cloned on a high-copy-number plasmid.
    J Bacteriol. 1990 Jan;172(1):437-45 PMID: 2152912
  31. marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli.
    J Bacteriol. 1988 Dec;170(12):5416-22 PMID: 2848006
  32. 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):1318-25 PMID: 2679373
  33. Standard reference strains of Escherichia coli from natural populations.
    J Bacteriol. 1984 Feb;157(2):690-3 PMID: 6363394
  34. Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway.
    J Bacteriol. 1993 Dec;175(24):7856-62 PMID: 7504664
  35. Salicylic acid: a systemic signal in induced plant disease resistance.
    Trends Microbiol. 1993 Jun;1(3):88-92 PMID: 8143122
  36. Chromosomal transformation of Escherichia coli recD strains with linearized plasmids.
    J Bacteriol. 1989 May;171(5):2609-13 PMID: 2651408
  37. Genetic relationship between soxRS and mar loci in promoting multiple antibiotic resistance in Escherichia coli.
    Antimicrob Agents Chemother. 1994 Aug;38(8):1773-9 PMID: 7986007
  38. Structure of the gene encoding the exoglucanase of Cellulomonas fimi.
    Gene. 1986;44(2-3):325-30 PMID: 3096818
  39. Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu.
    J Mol Biol. 1976 Jul 5;104(3):541-55 PMID: 781293
  40. Control site location and transcriptional regulation in Escherichia coli.
    Microbiol Rev. 1991 Sep;55(3):371-94 PMID: 1943993
  41. An operon of Bacillus subtilis motility genes transcribed by the sigma D form of RNA polymerase.
    J Bacteriol. 1992 Jul;174(13):4197-204 PMID: 1624413
  42. Bacterial resistance to the quinolone antimicrobial agents.
    Am J Med. 1989 Dec 29;87(6C):17S-23S PMID: 2690616
Article Info
Journal
Molecular medicine (Cambridge, Mass.)
Abbr.
Mol Med
ISSN
1076-1551
Published
1995-05-00
Pages
436-46
Language
English
Region
England
NLM ID
9501023
PMCID
PMC2230000
Subset
IM
Databases
GENBANK
L11080, M77238, M96235, S56952, X52480, X54141, X57175, X62158, X74409, Z12113
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