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JAC Advance Access originally published online on September 10, 2009
Journal of Antimicrobial Chemotherapy 2009 64(5):965-972; doi:10.1093/jac/dkp311
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Periplasmic adaptor protein AcrA has a distinct role in the antibiotic resistance and virulence of Salmonella enterica serovar Typhimurium

Jessica M. A. Blair1, Roberto M. La Ragione2, Martin J. Woodward2 and Laura J. V. Piddock1,*

1 School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK 2 Department of Food & Environmental Safety, Veterinary Laboratories Agency, Weybridge, Surrey, UK

Received 24 June 2009; returned 21 July 2009; revised 3 August 2009; accepted 4 August 2009

* Corresponding author. Tel: +44-121-414-6966; Fax: +44-121-414-6819; E-mail: l.j.v.piddock{at}bham.ac.uk

Objectives: AcrA can function as the periplasmic adaptor protein (PAP) in several RND tripartite efflux pumps, of which AcrAB-TolC is considered the most important. This system confers innate multiple antibiotic resistance. Disruption of acrB or tolC impairs the ability of Salmonella Typhimurium to colonize and persist in the host. The aim of this study was to investigate the role of AcrA alone in multidrug resistance and pathogenicity.

Methods: The acrA gene was inactivated in Salmonella Typhimurium SL1344 by insertion of the aph gene and this mutant complemented with pWKS30acrA. The antimicrobial susceptibility of the mutant to six antibiotics as well as various dyes and detergents was determined. In addition, efflux activity was quantified. The ability of the mutant to adhere to, and invade, tissue culture cells in vitro was measured.

Results: Following disruption of acrA, RT–PCR and western blotting confirmed that acrB/AcrB was still expressed when acrA was disrupted. The acrA mutant was hypersusceptible to antibiotics, dyes and detergents. In some cases, lower MICs were seen than for the acrB or tolC mutants. Efflux of the fluorescent dye Hoechst H33342 [GenBank] was less than in wild-type following disruption of acrA. acrA was also required for adherence to, and invasion of, tissue culture cells.

Conclusions: Inactivation of acrA conferred a phenotype distinct to that of acrB::aph and tolC::aph. These data indicate a role for AcrA distinct to that of other protein partners in both efflux of substrates and virulence.

Keywords: AcrAB-TolC , efflux , pathogenicity


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