Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure

Stephen Baker, Pham Thanh Duy, Tran Vu Thieu Nga, Tran Thi Ngoc Dung, Voong Vinh Phat, Tran Thuy Chau, A. Keith Turner, Jeremy Farrar, Maciej F. Boni

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere01229
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Dec 10 2013

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Salmonella typhi
Salmonella
Fluoroquinolones
Pressure
Mutation
Molecular Epidemiology
Typhoid Fever
Bacteria
Genes
Costs and Cost Analysis
Infection
Pharmaceutical Preparations
Costs
Experiments

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Baker, S., Duy, P. T., Nga, T. V. T., Dung, T. T. N., Phat, V. V., Chau, T. T., ... Boni, M. F. (2013). Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. eLife, 2013(2), [e01229]. https://doi.org/10.7554/eLife.01229.001
Baker, Stephen ; Duy, Pham Thanh ; Nga, Tran Vu Thieu ; Dung, Tran Thi Ngoc ; Phat, Voong Vinh ; Chau, Tran Thuy ; Keith Turner, A. ; Farrar, Jeremy ; Boni, Maciej F. / Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. In: eLife. 2013 ; Vol. 2013, No. 2.
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Baker, S, Duy, PT, Nga, TVT, Dung, TTN, Phat, VV, Chau, TT, Keith Turner, A, Farrar, J & Boni, MF 2013, 'Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure', eLife, vol. 2013, no. 2, e01229. https://doi.org/10.7554/eLife.01229.001

Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. / Baker, Stephen; Duy, Pham Thanh; Nga, Tran Vu Thieu; Dung, Tran Thi Ngoc; Phat, Voong Vinh; Chau, Tran Thuy; Keith Turner, A.; Farrar, Jeremy; Boni, Maciej F.

In: eLife, Vol. 2013, No. 2, e01229, 10.12.2013.

Research output: Contribution to journalArticle

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