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


CONCLUSIONS
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.
Unité BioAgresseurs, Santé et Environnement, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Sylvie
S
Baucheron
Elisabeth
E
Chaslus-Dancla
Axel
A
Cloeckaert
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D027101:DNA Topoisomerase IV / Q000235:genetics / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D009154:Mutation; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; C073126:tolC protein, E coli; D027101:DNA Topoisomerase IV