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Antimicrobial Agents and Chemotherapy, July 2005, p. 2746-2752, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2746-2752.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Constitutive soxR Mutations Contribute to Multiple-Antibiotic Resistance in Clinical Escherichia coli Isolates

Anastasia Koutsolioutsou, Samuel Peña-Llopis, and Bruce Demple*

Department of Genetics and Complex Diseases and Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts 02115

Received 11 January 2005/ Returned for modification 7 February 2005/ Accepted 7 March 2005

The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.


* Corresponding author. Mailing address: Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. Phone: (617) 432-3462. Fax: (617) 432-2590. E-mail: bdemple{at}hsph.harvard.edu.


Antimicrobial Agents and Chemotherapy, July 2005, p. 2746-2752, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2746-2752.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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