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The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence.
J Bacteriol. 1997 Mar; 179(6):1857-66.JB

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.

Authors+Show Affiliations

Therapeutics Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48106-1047, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9068629

Citation

Sulavik, M C., et al. "The Salmonella Typhimurium Mar Locus: Molecular and Genetic Analyses and Assessment of Its Role in Virulence." Journal of Bacteriology, vol. 179, no. 6, 1997, pp. 1857-66.
Sulavik MC, Dazer M, Miller PF. The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence. J Bacteriol. 1997;179(6):1857-66.
Sulavik, M. C., Dazer, M., & Miller, P. F. (1997). The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence. Journal of Bacteriology, 179(6), 1857-66.
Sulavik MC, Dazer M, Miller PF. The Salmonella Typhimurium Mar Locus: Molecular and Genetic Analyses and Assessment of Its Role in Virulence. J Bacteriol. 1997;179(6):1857-66. PubMed PMID: 9068629.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence. AU - Sulavik,M C, AU - Dazer,M, AU - Miller,P F, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 1857 EP - 66 JF - Journal of bacteriology JO - J Bacteriol VL - 179 IS - 6 N2 - 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. SN - 0021-9193 UR - https://www.unboundmedicine.com/medline/citation/9068629/The_Salmonella_typhimurium_mar_locus:_molecular_and_genetic_analyses_and_assessment_of_its_role_in_virulence_ L2 - http://jb.asm.org/cgi/pmidlookup?view=long&pmid=9068629 DB - PRIME DP - Unbound Medicine ER -