Abstract
Antibiotic resistance carries a fitness cost that could potentially limit the spread of resistance in bacterial pathogens. In spite of this cost, a large number of experimental evolution studies have found that resistance is stably maintained in the absence of antibiotics as a result of compensatory evolution. Clinical studies, on the other hand, have found that resistance in pathogen populations usually declines after antibiotic use is stopped, suggesting that compensatory adaptation is not effective in vivo. In this article, we argue that this disagreement arises because there are limits to compensatory adaptation in nature that are not captured by the design of current laboratory selection experiments. First, clinical treatment fails to eradicate antibiotic-sensitive strains, and competition between sensitive and resistant strains leads to the rapid loss of resistance following treatment. Second, laboratory studies overestimate the efficacy of compensatory adaptation in nature by failing to capture costs associated with compensatory mutations. Taken together, these ideas can potentially reconcile evolutionary theory with the clinical dynamics of antibiotic resistance and guide the development of strategies for containing resistance in clinical pathogens.
Highlights
Evolving antibiotic resistance by horizontal gene transfer or by chromosomal mutation is associated with a fitness cost, as demonstrated by the fact that resistant bacteria have reduced growth rates and competitive ability relative to sensitive strains in the absence of antibiotics [1,2,3,4,5]
They found that resistance was stably maintained in the absence of antibiotics because resistant clones adapted to the cost of resistance by evolving second-site compensatory mutations that recovered the cost of resistance [11]
If compensatory adaptation is commonplace in clinical bacterial pathogens, resistance should be maintained after antibiotic use is discontinued
Summary
Evolving antibiotic resistance by horizontal gene transfer or by chromosomal mutation is associated with a fitness cost, as demonstrated by the fact that resistant bacteria have reduced growth rates and competitive ability relative to sensitive strains in the absence of antibiotics [1,2,3,4,5]. These studies do not control for genetic background and fitness is measured in the laboratory, rather than in a natural environments These studies clearly support the idea that compensatory adaptation is unable to maintain resistance in clinical settings. On the other hand, find that resistance usually declines when antibiotic use is stopped or discontinued, and resistant strains usually have lower fitness than conspecific-sensitive strains These results suggest that selection for compensatory adaptation is not able to stabilize resistance in natural populations of pathogenic bacteria
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
