Evolution of Cost-Free Resistance under Fluctuating Drug Selection in .

Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen under conditions of constant and fluctuating antibiotic delivery patterns.

The fitness costs of antibiotic resistance mutations.

Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment.

Evolutionary insight from whole-genome sequencing of experimentally evolved microbes.

Experimental evolution (EE) combined with whole-genome sequencing (WGS) has become a compelling approach to study the fundamental mechanisms and processes that drive evolution. Most EE-WGS studies published to date have used microbes, owing to their ease of propagation and manipulation in the laboratory and relatively small genome sizes. These experiments are particularly suited to answer long-standing questions such as: How many mutations underlie adaptive evolution, and how are they distributed across the genome and through time? Are there general rules or principles governing which genes contribute to adaptation, and are certain kinds of genes more likely to be targets than others? How common is epistasis among adaptive mutations, and what does this reveal about the variety of genetic routes to adaptation? How common is parallel evolution, where the same mutations evolve repeatedly and independently in response to similar selective pressures? Here, we summarize the significant findings of this body of work, identify important emerging trends and propose promising directions for future research.

Adaptive landscapes in evolving populations of Pseudomonas fluorescens.

The repeatability of adaptive evolution depends on the ruggedness of the underlying adaptive landscape. We contrasted the relative ruggedness of two adaptive landscapes by measuring the variance in fitness and metabolic phenotype within and among genetically distinct strains of Pseudomonas fluorescens in two environments differing only in the carbon source provided (glucose vs. xylose).