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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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.7554/eLife.01229.001

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Publisher:
eLife Sciences Publications
Journal:
eLife More from this journal
Volume:
2013
Issue:
2
Article number:
e01229
Publication date:
2013-12-10
Acceptance date:
2013-10-22
DOI:
EISSN:
2050-084X


Language:
English
Keywords:
UUID:
uuid:1e6caaf8-7875-4a29-a2a4-8f6a1551da1f
Local pid:
pubs:444661
Source identifiers:
444661
Deposit date:
2014-01-30

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