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Antimicrobial Agents and Chemotherapy, January 2001, p. 38-43, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.38-43.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A soxRS-Constitutive Mutation Contributing to Antibiotic Resistance in a Clinical Isolate of Salmonella enterica (Serovar Typhimurium)

Anastasia Koutsolioutsou,1 Elizabeth A. Martins,1,dagger D. G. White,2,Dagger S. B. Levy,2 and Bruce Demple1,*

Department of Cancer Cell Biology and Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts 02115,1 and Center for Adaptation Genetics and Drug Resistance, Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 021112

Received 20 April 2000/Returned for modification 1 June 2000/Accepted 29 September 2000

The soxRS regulon is activated by redox-cycling drugs such as paraquat and by nitric oxide. The >15 genes of this system provide resistance to both oxidants and multiple antibiotics. An association between clinical quinolone resistance and elevated expression of the soxRS regulon has been observed in Escherichia coli, but this association has not been explored for other enteropathogenic bacteria. Here we describe a soxRS-constitutive mutation in a clinical strain of Salmonella enterica (serovar Typhimurium) that arose with the development of resistance to quinolones during treatment. The elevated quinolone resistance in this strain derived from a point mutation in the soxR gene and could be suppressed in trans by multicopy wild-type soxRS. Multiple-antibiotic resistance was also transferred to a laboratory strain of S. enterica by introducing the cloned mutant soxR gene from the clinical strain. The results show that constitutive expression of soxRS can contribute to antibiotic resistance in clinically relevant S. enterica.

* Corresponding author. Mailing address: Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. Phone: (617) 432-3462. Fax: (617) 432-0377. E-mail: bdemple{at}hsph.harvard.edu.

dagger Present address: Centro de Biotechnología, Instituto Butantan, São Paulo, Brazil.

Dagger Present address: Center for Veterinary Medicine, U.S. Food & Drug Administration, Laurel, MD 20708.

Antimicrobial Agents and Chemotherapy, January 2001, p. 38-43, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.38-43.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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