title: Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium.
abstract: 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 micro g 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 micro g 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.
authors.affiliation: Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Giraud
authors.affiliation: Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Cloeckaert
authors.affiliation: Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Baucheron
authors.affiliation: Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Mouline
authors.affiliation: Unité Bio-Agresseurs, Santé, Environnement, Institut National de la Recherche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Chaslus-Dancla
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002645:Chickens / Q000382:microbiology; D002939:Ciprofloxacin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics* / Q000502:physiology; D019143:Evolution, Molecular; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin