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 journalArticlepeer-review

69 Scopus citations

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

All Science Journal Classification (ASJC) codes

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

Fingerprint Dive into the research topics of 'Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure'. Together they form a unique fingerprint.

Cite this