Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium

Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France Correspondence Elisabeth Chaslus-Dancla chaslus{at}tours.inra.fr Received January 14, 2003 Accepted April 16, 2003 High-level fluoroquinolone (FQ) resistance is still infrequent in salmonellae, compared with other pathogenic enterobacteria. Data provided in this work support the hypothesis that the mechanisms that confer high-level FQ resistance on salmonellae have a prohibitive fitness cost and may thus limit the emergence of highly resistant clones. In vitro mutants that were highly resistant to ciprofloxacin (MIC = 8 and 16 µg ml -1 ) showed generation times 1.4- and 2-fold longer than their parent strains and were unable to colonize the gut of chickens. Electron microscopy showed an altered morphology for one of these mutants grown to stationary phase. Mutants selected in vivo and exhibiting intermediate resistance to ciprofloxacin (MIC = 2 µg ml -1 ) also showed growth defects on solid media but had normal generation times in liquid culture and colonized the gut of chickens. After in vitro or in vivo passage in the absence of antibiotic selective pressure, partial reversals of the fitness cost were observed, which were associated with slight decreases in resistance to quinolones and other unrelated antibiotics, but were not linked to the loss of gyrA mutations. Present address: UMR INRA/ENVN Chimiothérapie Aquacole et Environnement, Ecole Nationale Vétérinaire de Nantes, Atlanpole – La Chantrerie, BP 40706, 44307 Nantes Cedex 03, France. Abbreviation: FQ, fluoroquinolone.