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

J Antimicrob Chemother. 2004 Apr;53(4):657-9. doi: 10.1093/jac/dkh122. Epub 2004 Feb 25.


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 (DeltatolC) 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 DeltatolC 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 DeltatolC transductants, concomitant loss of the parC (Ser-80-->Ile) mutation, located approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / physiology*
  • DNA Topoisomerase IV / genetics
  • DNA Topoisomerase IV / physiology*
  • Drug Resistance, Bacterial / genetics*
  • Escherichia coli Proteins
  • Fluoroquinolones / pharmacology*
  • Membrane Transport Proteins
  • Mutation*
  • Salmonella enterica / drug effects
  • Salmonella enterica / genetics
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*


  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Fluoroquinolones
  • Membrane Transport Proteins
  • tolC protein, E coli
  • DNA Topoisomerase IV