Journal Article

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

Sylvie Baucheron, Elisabeth Chaslus-Dancla and Axel Cloeckaert

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 4, pages 657-659
Published in print April 2004 | ISSN: 0305-7453
Published online April 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh122
Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204

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

Journal Article.  1700 words. 

Subjects: Medical Oncology ; Critical Care

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