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JAC Advance Access published online on February 25, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh122
© 2004 by The British Society for Antimicrobial Chemotherapy
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© 2004

Brief reports

Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204

Sylvie Baucheron 1 , Elisabeth Chaslus-Dancla 1 , and Axel Cloeckaert 1 *

1 Unité BioAgresseurs, Santé et Environnement, Institut National de la Recherche Agronomique, 37380 Nouzilly, France

* Corresponding author. E-mail: cloeckae{at}tours.inra.fr.

Received 27 November 2003 ; revised 18 December 2003 ; accepted 19 December 2003

Abstract

Objectives: To study the role of TolC and of parC mutation in high-level fluoroquinolone resistance in clonal clinical strains of Salmonella enterica serotype Typhimurium phage type DT204 (S. Typhimurium DT204).

Methods: Deletion of the tolC gene ({Delta}tolC) was first performed in a susceptible S. Typhimurium DT104 strain lacking target gene mutations involved in fluoroquinolone resistance. P22 transduction was further used to transduce {Delta}tolC from this strain to a high-level fluoroquinolone-resistant S. Typhimurium DT204 strain carrying several target gene mutations, including one in parC (ciprofloxacin MIC of 32 mg/L).

Results: Deletion of tolC in the high-level fluoroquinolone-resistant S. Typhimurium DT204 strain resulted in the same decrease in resistance levels (16- to 32-fold) as shown previously for an acrB mutant of the same strain, suggesting that AcrAB-TolC is the main efflux system involved in high-level fluoroquinolone resistance of S. Typhimurium DT204 strains. In some S. Typhimurium DT204 {Delta}tolC transductants, concomitant loss of the parC (Ser-80->Ile) mutation, located ~9.3 kb upstream of tolC, resulted in a further 16- to 32-fold decrease in resistance levels to fluoroquinolones and thus a hypersusceptible phenotype (ciprofloxacin MIC of 0.063 mg/L).

Conclusion: The AcrAB-TolC efflux system, together with multiple target gene mutations, including the parC mutation, appear essential to confer high-level fluoroquinolone resistance in S. Typhimurium DT204.

Keywords: salmonellosis, multidrug resistance, AcrAB-TolC efflux system, multidrug transporter AcrB, outer membrane component TolC, target gene
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