Why doesn't the evolution of antibiotic resistance have a larger fitness cost?

Antibiotic resistance is a major threat to human health and well-being, as well as food production and animal welfare. There is a pressing need to better our understanding of the evolutionary dynamics of antibiotic resistance, particularly about what happens when selection for resistance is removed. The primary driver of resistance is the ongoing consumption of antibiotics, with the frequency of resistance rising in winter and declining in summer, which matches patterns of antibiotic prescribing. We explain these seasonal shifts in the prevalence of resistance with the concept of resistance having a fitness cost, whereby resistant bacteria are less competitive or successful than non-resistant bacteria when antibiotics are not present. However the evidence for the existence of fitness costs is mixed. Although resistance is costly on average, and most resistance mutations do have a cost, more than 10% of resistance mutations and 20% of resistance carrying mobile genetic elements have either no detectable fitness cost or are beneficial (1). This raises two possibilities: either our current methodologies for detecting costs are significantly flawed, or we have complexly misinterpreted the ecological dynamics of antibiotic resistance.

This project will explore the fitness costs of antibiotic resistance using laboratory microbiology, data synthesis, and comparative genomics. It will seek to answer:
(i) Can a mutation really have no fitness cost?
(ii) Why should a mobile genetic element have a fitness cost?
For the former, there are a range of ideas which could explain why a costly mutation might appear to be cost free. These include laboratory environments being highly artificial, mutations could be costly in some environments but not all, or the cost of resistance existing for certain species or strains but not others. This part of the project will us experimental evolution and laboratory microbiology to separate these competing explanations. The project will then go on to take advantage of the huge number of publicly available bacterial genomes to link the frequency and properties of mobile genetic elements to pathogen and non-pathogen life-history traits.

The project provides a great opportunity to understand the evolutionary biology of antibiotic resistance and receive world class training in modern evolutionary microbiology and comparative genomics. The project will be based at the University of Aberdeen under the lead supervision of Dr Tom Vogwill, an evolutionary microbiologist with expertise in antibiotic resistance and microbial evolutionary ecology. The project will be co-supervised by Professor Nick Colegrave at the University of Edinburgh, with expertise in evolutionary theory and microbiology.

References
(1) Vogwill, T & MacLean, RC (2015): The genetic basis of the fitness costs of antimicrobial resistance: a meta-analysis approach. Evol Appl 8: 284-295.
(2) MacLean, RC & Vogwill, T (2015): Limits to compensatory adaptation and the persistence of antibiotic resistance in pathogenic bacteria. Evolution, Medicine, and Public Health, Volume 2015, Issue 1, Pages 4-12.
(3) MacLean, RC & San Millan, A (2015): Microbial Evolution: Towards Resolving the Plasmid Paradox. Current Biology 25 (17), R764-R767.