Home LiteratureArticle Details
PMID: 9068629 Published · ppublish English Journal Article

The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence.

Journal of bacteriology ·Vol. 179 ·No. 6 ·1997-03-00 ·Pages 1857-66

Sulavik MC, Dazer M, Miller PF

Abstract

The marRAB operon is a regulatory locus that controls multiple drug resistance in Escherichia coli. marA encodes a positive regulator of the antibiotic resistance response, acting by altering the expression of unlinked genes. marR encodes a repressor of marRAB transcription and controls the production of MarA in response to environmental signals. A molecular and genetic study of the homologous operon in Salmonella typhimurium was undertaken, and the role of marA in virulence in a murine model was assessed. Expression of E. coli marA (marAEC) present on a multicopy plasmid in S. typhimurium resulted in a multiple antibiotic resistance (Mar) phenotype, suggesting that a similar regulon exists in this organism. A genomic plasmid library containing S. typhimurium chromosomal sequences was introduced into an E. coli strain that was deleted for the mar locus and contained a single-copy marR'-'lacZ translational fusion. Plasmid clones that contained both S. typhimurium marR (marRSt) and marA (marASt) genes were identified as those that were capable of repressing expression of the fusion and which resulted in a Mar phenotype. The predicted amino acid sequences of MarRSt, MarASt, and MarBSt were 91, 86, and 42% identical, respectively, to the same genes from E. coli, while the operator/promoter region of the operon was 86% identical to the same 98-nucleotide-upstream region in E. coli. The marRAB transcriptional start sites for both organisms were determined by primer extension, and a marRABSt transcript of approximately 1.1 kb was identified by Northern blot analysis. Its accumulation was shown to be inducible by sodium salicylate. Open reading frames flanking the marRAB operon were also conserved. An S. typhimurium marA disruption strain was constructed by an allelic exchange method and compared to the wild-type strain for virulence in a murine BALB/c infection model. No effect on virulence was noted. The endogenous S. typhimurium plasmid that is associated with virulence played no role in marA-mediated multiple antibiotic resistance. Taken together, the data show that the S. typhimurium mar locus is structurally and functionally similar to marRABEc and that a lesion in marASt has no effect on S. typhimurium virulence for BALB/c mice.

MeSH Terms
Amino Acid Sequence Animals Bacterial Proteins/genetics Base Sequence Blotting, Northern Cloning, Molecular DNA-Binding Proteins/genetics Drug Resistance, Microbial/genetics Drug Resistance, Multiple/genetics Escherichia coli Proteins Female Genetic Complementation Test Mice Mice, Inbred BALB C Molecular Sequence Data Open Reading Frames Operon Plasmids Promoter Regions, Genetic Repressor Proteins/genetics Salmonella Infections, Animal/microbiology Salmonella typhimurium/drug effects,genetics,pathogenicity Sequence Analysis, DNA Transcription, Genetic Virulence/genetics
Chemicals
Bacterial Proteins DNA-Binding Proteins Escherichia coli Proteins MarA protein, E coli MarR protein, E coli Repressor Proteins multiple antibiotic resistance protein B
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sulavik M C
Therapeutics Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48106-1047, USA.
Dazer M
Miller P F
References (55)
55 references, click to expand
  1. 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
  2. Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli.
    Mol Microbiol. 1996 Aug;21(3):441-8 PMID: 8866468
  3. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system.
    Gene. 1977;2(2):95-113 PMID: 344137
  4. Association of adhesive, invasive, and virulent phenotypes of Salmonella typhimurium with autonomous 60-megadalton plasmids.
    Infect Immun. 1982 Nov;38(2):476-86 PMID: 6128304
  5. In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid.
    Antimicrob Agents Chemother. 1983 May;23(5):641-8 PMID: 6575721
  6. 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
  7. 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
  8. Salmonella typhimurium LT2 strains which are r- m+ for all three chromosomally located systems of DNA restriction and modification.
    J Bacteriol. 1983 Oct;156(1):471-4 PMID: 6352690
  9. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  10. 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
  11. 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
  12. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  13. Plasmid-associated virulence of Salmonella typhimurium.
    Infect Immun. 1987 Dec;55(12):2891-901 PMID: 3316027
  14. 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
  15. One-step preparation of competent Escherichia coli: transformation and storage of bacterial cells in the same solution.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2172-5 PMID: 2648393
  16. 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):283-90 PMID: 2658782
  17. New method for generating deletions and gene replacements in Escherichia coli.
    J Bacteriol. 1989 Sep;171(9):4617-22 PMID: 2548993
  18. 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
  19. Bacterial resistance to the quinolone antimicrobial agents.
    Am J Med. 1989 Dec 29;87(6C):17S-23S PMID: 2690616
  20. soxR, a locus governing a superoxide response regulon in Escherichia coli K-12.
    J Bacteriol. 1990 Aug;172(8):4197-205 PMID: 1695893
  21. 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
  22. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  23. Transposon-facilitated DNA sequencing.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1247-50 PMID: 1847513
  24. Pyruvate-formate-lyase-deactivase and acetyl-CoA reductase activities of Escherichia coli reside on a polymeric protein particle encoded by adhE.
    FEBS Lett. 1991 Apr 9;281(1-2):59-63 PMID: 2015910
  25. Activation of oxidative stress genes by mutations at the soxQ/cfxB/marA locus of Escherichia coli.
    J Bacteriol. 1991 Jul;173(14):4433-9 PMID: 1648558
  26. marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli.
    J Bacteriol. 1991 Sep;173(17):5532-8 PMID: 1715857
  27. Allelic exchange in Escherichia coli using the Bacillus subtilis sacB gene and a temperature-sensitive pSC101 replicon.
    Mol Microbiol. 1991 Jun;5(6):1447-57 PMID: 1686293
  28. 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):6054-60 PMID: 1400156
  29. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli.
    J Bacteriol. 1993 Mar;175(5):1484-92 PMID: 8383113
  30. 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
  31. A multidrug resistance regulatory chromosomal locus is widespread among enteric bacteria.
    J Infect Dis. 1993 Aug;168(2):484-8 PMID: 8335992
  32. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages.
    Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9993-7 PMID: 8234347
  33. 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
  34. 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
  35. A cytolysin encoded by Salmonella is required for survival within macrophages.
    Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):489-93 PMID: 8290552
  36. 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
  37. pecS: a locus controlling pectinase, cellulase and blue pigment production in Erwinia chrysanthemi.
    Mol Microbiol. 1994 Mar;11(6):1127-39 PMID: 8022282
  38. 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
  39. 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
  40. 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
  41. Identification of new genes regulated by the marRAB operon in Escherichia coli.
    J Bacteriol. 1995 Feb;177(3):530-5 PMID: 7836283
  42. Roles of nitric oxide in inducible resistance of Escherichia coli to activated murine macrophages.
    Infect Immun. 1995 Mar;63(3):794-8 PMID: 7532626
  43. Activation of multiple antibiotic resistance and binding of stress-inducible promoters by Escherichia coli Rob protein.
    J Bacteriol. 1995 Apr;177(7):1655-61 PMID: 7896685
  44. Characterization of MarR, the repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli.
    J Bacteriol. 1995 Jun;177(12):3414-9 PMID: 7768850
  45. 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):5456-60 PMID: 7777530
  46. Regulation of the multiple antibiotic resistance (mar) regulon by marORA sequences in Escherichia coli.
    J Bacteriol. 1995 Jul;177(14):4176-8 PMID: 7608098
  47. Sequence of a transposon identified as Tn1000 (gamma delta).
    DNA Seq. 1995;5(3):185-9 PMID: 7612932
  48. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli.
    Mol Microbiol. 1995 Apr;16(1):45-55 PMID: 7651136
  49. 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.
    Mol Med. 1995 May;1(4):436-46 PMID: 8521301
  50. Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic and superoxide resistance promoters.
    J Bacteriol. 1995 Dec;177(24):7100-4 PMID: 8522515
  51. How Salmonella survive against the odds.
    Annu Rev Microbiol. 1995;49:145-74 PMID: 8561457
  52. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants.
    J Bacteriol. 1996 Jan;178(1):306-8 PMID: 8550435
  53. Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli.
    J Bacteriol. 1996 Apr;178(8):2216-23 PMID: 8636021
  54. Multiple antibiotic resistance (mar) locus protects Escherichia coli from rapid cell killing by fluoroquinolones.
    Antimicrob Agents Chemother. 1996 May;40(5):1266-9 PMID: 8723480
  55. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/jb.179.6.1857-1866.1997
Published
1997-03-00
Pages
1857-66
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC178907
Subset
IM
Databases
GENBANK
U54468
External Links
PubMed source DOI: 10.1128/jb.179.6.1857-1866.1997 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2