The costs of evolving resistance in heterogeneous parasite environments

Abstract

The evolution of host resistance to parasites, shaped by associated fitness costs, is crucial for epidemiology and maintenance of genetic diversity. Selection imposed by multiple parasites could be a particularly strong constraint, as hosts either accumulate costs of multiple specific resistances or evolve a more costly general resistance mechanism. We used experimental evolution to test how parasite heterogeneity influences the evolution of host resistance. We show that bacterial host populations evolved specific resistance to local bacteriophage parasites, regardless of whether they were in single or multiple-phage environments, and that hosts evolving with multiple phages were no more resistant to novel phages than those evolving with single phages. However, hosts from multiple-phage environments paid a higher cost, in terms of population growth in the absence of phage, for their evolved specific resistances than those from single-phage environments. Given that in nature host populations face selection pressures from multiple parasite strains and species, our results suggest that costs may be even more critical in shaping the evolution of resistance than previously thought. Furthermore, our results highlight that a better understanding of resistance costs under combined control strategies could lead to a more 'evolution-resistant' treatment of disease.

Figure 1.

Experimental evolution methods. Three individual bacterium, representing each of three bacterial genotypes, were used to generate replicate populations experiencing one of three selection regimes (no-phage, single-phage or multiple-phage environment) over the course of approximately 130 bacterial generations. Numbers represent phage treatment (i.e. single phage or combinations of three out of the four phages).

Figure 2.

Evolved resistance across replicate bacterial lines of each genotype according to selection regime. Six individual bacterial clones (i.e. colonies) from each bacterial population were streaked across a given phage inoculum and the mean proportion of resistant colonies per population is shown. Error bars represent ±1 s.e.m.

Figure 3.

Bacterial resistance to phages with which the bacterial lines were evolved (black, sympatric) and phages not present during evolution (grey, allopatric). Control populations are not included, as they had no associated sympatric phages. The mean proportion of resistant colonies per population is shown. Error bars represent ±1 s.e.m.

Figure 4.

Population growth, in the absence of phage, of experimental strains at the end of the experiment. Bacterial density was measured every 5 min at an optical density (OD) of 600 nm, and mean growth over each hour (±1 s.e.m.) for 20 h is shown.