%0 Journal Article %1 Baker2013Fitness %A Baker, Stephen %A Duy, Pham Thanh T. %A Nga, Tran Vu Thieu V. %A Dung, Tran Thi Ngoc T. %A Phat, Voong Vinh V. %A Chau, Tran Thuy T. %A Turner, A. Keith %A Farrar, Jeremy %A Boni, Maciej F. %D 2013 %I eLife Sciences Publications Limited %J eLife %K drug-resistance fitness selection-pressure %R 10.7554/elife.01229 %T Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. %U http://dx.doi.org/10.7554/elife.01229 %V 2 %X 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.

@article{Baker2013Fitness, 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. }, added-at = {2018-12-02T16:09:07.000+0100}, author = {Baker, Stephen and Duy, Pham Thanh T. and Nga, Tran Vu Thieu V. and Dung, Tran Thi Ngoc T. and Phat, Voong Vinh V. and Chau, Tran Thuy T. and Turner, A. Keith and Farrar, Jeremy and Boni, Maciej F.}, biburl = {https://www.bibsonomy.org/bibtex/2db851ad066cf3d833ca73dd98202e4d7/karthikraman}, citeulike-article-id = {12889090}, citeulike-linkout-0 = {http://dx.doi.org/10.7554/elife.01229}, citeulike-linkout-1 = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857714/}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/24327559}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=24327559}, day = 10, doi = {10.7554/elife.01229}, interhash = {d9ea964c426d16684945b8a2586033a1}, intrahash = {db851ad066cf3d833ca73dd98202e4d7}, issn = {2050-084X}, journal = {eLife}, keywords = {drug-resistance fitness selection-pressure}, month = dec, pmcid = {PMC3857714}, pmid = {24327559}, posted-at = {2014-03-17 09:58:08}, priority = {2}, publisher = {eLife Sciences Publications Limited}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure.}, url = {http://dx.doi.org/10.7554/elife.01229}, volume = 2, year = 2013 }