title: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.
abstract: Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
authors.affiliation: Institute of Integrative Biology, ETH Zürich, 8092 Zürich, Switzerland sebastien.wielgoss@env.ethz.ch alex.hall@env.ethz.ch.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wielgoss
authors.affiliation: IST Austria, Klosterneuburg, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bergmiller
authors.affiliation: Institute of Integrative Biology, ETH Zürich, 8092 Zürich, Switzerland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bischofberger
authors.affiliation: Institute of Integrative Biology, ETH Zürich, 8092 Zürich, Switzerland sebastien.wielgoss@env.ethz.ch alex.hall@env.ethz.ch.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Hall
mesh_terms: D000220:Adaptation, Biological; D001419:Bacteria / Q000235:genetics* / Q000821:virology*; D001435:Bacteriophages / Q000502:physiology; D005075:Biological Evolution; D056084:Genetic Fitness; D014644:Genetic Variation; D054884:Host-Pathogen Interactions; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
keywords: bacteriophages.; coevolution; experimental evolution; mutation rate