title: Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure.
abstract: Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced. DOI: http://dx.doi.org/10.7554/eLife.01229.001.
authors: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors: Stephen
authors: S
authors: Baker
authors: Pham Thanh
authors: PT
authors: Duy
authors: Tran Vu Thieu
authors: TV
authors: Nga
authors: Tran Thi Ngoc
authors: TT
authors: Dung
authors: Voong Vinh
authors: VV
authors: Phat
authors: Tran Thuy
authors: TT
authors: Chau
authors: A Keith
authors: AK
authors: Turner
authors: Jeremy
authors: J
authors: Farrar
authors: Maciej F
authors: MF
authors: Boni
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004843:Epistasis, Genetic / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012485:Salmonella typhi / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: Salmonella; epistasis; fitness cost; fluoroquinolone; typhoid