Abstract
The evolution of antibiotic resistance carries a fitness cost, expressed in terms of reduced competitive ability in the absence of antibiotics. This cost plays a key role in the dynamics of resistance by generating selection against resistance when bacteria encounter an antibiotic-free environment. Previous work has shown that the cost of resistance is highly variable, but the underlying causes remain poorly understood. Here, we use a meta-analysis of the published resistance literature to determine how the genetic basis of resistance influences its cost. We find that on average chromosomal resistance mutations carry a larger cost than acquiring resistance via a plasmid. This may explain why resistance often evolves by plasmid acquisition. Second, we find that the cost of plasmid acquisition increases with the breadth of its resistance range. This suggests a potentially important limit on the evolution of extensive multidrug resistance via plasmids. We also find that epistasis can significantly alter the cost of mutational resistance. Overall, our study shows that the cost of antimicrobial resistance can be partially explained by its genetic basis. It also highlights both the danger associated with plasmidborne resistance and the need to understand why resistance plasmids carry a relatively low cost.
Highlights
Antimicrobial resistance carries a fitness cost that is expressed in terms of reduced growth rate, competitive ability or virulence
We examine which factors contribute to the cost of plasmid-mediated resistance, testing whether resistance range, plasmid size or host genetic background contributes to the cost of plasmid acquisition
One of the most important challenges in understanding of antimicrobial resistance is to determine whether there are any broad, general features which can be applied across biological systems (Martinez et al 2007; zur Wiesch et al 2011)
Summary
Antimicrobial resistance carries a fitness cost that is expressed in terms of reduced growth rate, competitive ability or virulence (reviewed in Andersson 2006; Andersson and Hughes 2010) This cost of resistance is predicted to play a key role in the evolutionary dynamics of resistance because it generates selection against resistance (e.g. Austin et al 1997, 1999; Lipsitch et al 2000; zur Wiesch et al 2011). This is important when bacteria encounter an antibiotic-free environment, as occurs when patients stop using an antibiotic or during transmission between hosts Because of this central role, the costs of resistance have been measured in well over 100 studies spanning a wide diversity of resistance mechanisms and pathogens. It is perhaps not surprising that the cost of resistance is highly variable, as it is influenced by a wide variety of factors These include the biochemical effects of specific resistance mutations It is unlikely that we will ever be able to fully explain the cost of resistance
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