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RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium.
J Bacteriol. 2010 Mar; 192(6):1607-16.JB

Abstract

The transcriptomes of Salmonella enterica serovar Typhimurium SL1344 lacking a functional ramA or ramR or with plasmid-mediated high-level overexpression of ramA were compared to those of the wild-type parental strain. Inactivation of ramA led to increased expression of 14 SPI-1 genes and decreased expression of three SPI-2 genes, and it altered expression of ribosomal biosynthetic genes and several amino acid biosynthetic pathways. Furthermore, disruption of ramA led to decreased survival within RAW 264.7 mouse macrophages and attenuation within the BALB/c ByJ mouse model. Highly overexpressed ramA led to increased expression of genes encoding multidrug resistance (MDR) efflux pumps, including acrAB, acrEF, and tolC. Decreased expression of 34 Salmonella pathogenicity island (SPI) 1 and 2 genes, decreased SipC production, decreased adhesion to and survival within macrophages, and decreased colonization of Caenorhabditis elegans were also seen. Disruption of ramR led to the increased expression of ramA, acrAB, and tolC, but not to the same level as when ramA was overexpressed on a plasmid. Inactivation of ramR had a more limited effect on pathogenicity gene expression. In silico analysis of a suggested RamA-binding consensus sequence identified target genes, including ramR, acrA, tolC, sipABC, and ssrA. This study demonstrates that the regulation of a mechanism of MDR and expression of virulence genes show considerable overlap, and we postulate that such a mechanism is dependent on transcriptional activator concentration and promoter sensitivity. However, we have no evidence to support the hypothesis that increased MDR via RamA regulation of AcrAB-TolC gives rise to a hypervirulent strain.

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Authors+Show Affiliations

Bailey AM
Antimicrobial Agents Research Group, Department of Immunity and Infection, The Medical School, The University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Ivens A
No affiliation info available
Kingsley R
No affiliation info available
Cottell JL
No affiliation info available
Wain J
No affiliation info available
Piddock LJ
No affiliation info available

MeSH

AnimalsBacterial ProteinsCaenorhabditis elegansCarrier ProteinsCell LineFemaleGene Expression ProfilingGene Expression Regulation, BacterialMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLMultidrug Resistance-Associated ProteinsOligonucleotide Array Sequence AnalysisPorinsSalmonella InfectionsSalmonella typhimuriumTrans-ActivatorsVirulence

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20081028

Citation

Bailey, Andrew M., et al. "RamA, a Member of the AraC/XylS Family, Influences Both Virulence and Efflux in Salmonella Enterica Serovar Typhimurium." Journal of Bacteriology, vol. 192, no. 6, 2010, pp. 1607-16.
Bailey AM, Ivens A, Kingsley R, et al. RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J Bacteriol. 2010;192(6):1607-16.
Bailey, A. M., Ivens, A., Kingsley, R., Cottell, J. L., Wain, J., & Piddock, L. J. (2010). RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. Journal of Bacteriology, 192(6), 1607-16. https://doi.org/10.1128/JB.01517-09
Bailey AM, et al. RamA, a Member of the AraC/XylS Family, Influences Both Virulence and Efflux in Salmonella Enterica Serovar Typhimurium. J Bacteriol. 2010;192(6):1607-16. PubMed PMID: 20081028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. AU - Bailey,Andrew M, AU - Ivens,Al, AU - Kingsley,Rob, AU - Cottell,Jennifer L, AU - Wain,John, AU - Piddock,Laura J V, Y1 - 2010/01/15/ PY - 2010/1/19/entrez PY - 2010/1/19/pubmed PY - 2010/4/16/medline SP - 1607 EP - 16 JF - Journal of bacteriology JO - J Bacteriol VL - 192 IS - 6 N2 - The transcriptomes of Salmonella enterica serovar Typhimurium SL1344 lacking a functional ramA or ramR or with plasmid-mediated high-level overexpression of ramA were compared to those of the wild-type parental strain. Inactivation of ramA led to increased expression of 14 SPI-1 genes and decreased expression of three SPI-2 genes, and it altered expression of ribosomal biosynthetic genes and several amino acid biosynthetic pathways. Furthermore, disruption of ramA led to decreased survival within RAW 264.7 mouse macrophages and attenuation within the BALB/c ByJ mouse model. Highly overexpressed ramA led to increased expression of genes encoding multidrug resistance (MDR) efflux pumps, including acrAB, acrEF, and tolC. Decreased expression of 34 Salmonella pathogenicity island (SPI) 1 and 2 genes, decreased SipC production, decreased adhesion to and survival within macrophages, and decreased colonization of Caenorhabditis elegans were also seen. Disruption of ramR led to the increased expression of ramA, acrAB, and tolC, but not to the same level as when ramA was overexpressed on a plasmid. Inactivation of ramR had a more limited effect on pathogenicity gene expression. In silico analysis of a suggested RamA-binding consensus sequence identified target genes, including ramR, acrA, tolC, sipABC, and ssrA. This study demonstrates that the regulation of a mechanism of MDR and expression of virulence genes show considerable overlap, and we postulate that such a mechanism is dependent on transcriptional activator concentration and promoter sensitivity. However, we have no evidence to support the hypothesis that increased MDR via RamA regulation of AcrAB-TolC gives rise to a hypervirulent strain. SN - 1098-5530 UR - https://www.unboundmedicine.com/medline/citation/20081028/RamA_a_member_of_the_AraC/XylS_family_influences_both_virulence_and_efflux_in_Salmonella_enterica_serovar_Typhimurium_ L2 - https://journals.asm.org/doi/10.1128/JB.01517-09?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -