Journal
EVOLUTION
Volume 75, Issue 5, Pages 1230-1238Publisher
OXFORD UNIV PRESS
DOI: 10.1111/evo.14203
Keywords
Antimicrobial resistance; epistasis; genetic background; pleiotropy; relative fitness; trade‐ offs
Categories
Funding
- HHMI Gilliam Fellowship
- MSU Department of Microbiology and Molecular Genetics
- National Science Foundation [DEB-1951307]
- USDA [MICL02253]
- BEACON Center for the Study of Evolution in Action (National Science Foundation) [DBI-0939454]
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The study found that the fitness costs of antibiotic resistance are not always correlated with the phenotypic level of resistance or the underlying genetic changes, but are instead influenced by specific resistance mutations and the genetic backgrounds in which they occur.
A bacterium's fitness relative to its competitors, both in the presence and absence of antibiotics, plays a key role in its ecological success and clinical impact. In this study, we examine whether tetracycline-resistant mutants are less fit in the absence of the drug than their sensitive parents, and whether the fitness cost of resistance is constant or variable across independently derived lines. Tetracycline-resistant lines suffered, on average, a reduction in fitness of almost 8%. There was substantial among-line variation in the fitness cost. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary significantly across several genetic backgrounds. The two resistant lines with the most extreme fitness costs involved functionally unrelated mutations on different genetic backgrounds. However, there was also significant variation in the fitness costs for mutations affecting the same pathway and even different alleles of the same gene. Our findings demonstrate that the fitness costs of antibiotic resistance do not always correlate with the phenotypic level of resistance or the underlying genetic changes. Instead, these costs reflect the idiosyncratic effects of particular resistance mutations and the genetic backgrounds in which they occur.
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