The evolution of resistance against good and bad infections

Opportunities for genetic exchange are abundant between bacteria and foreign genetic elements (FGEs) such as conjugative plasmids, transposable elements and bacteriophages. The genetic novelty that may arise from these forms of genetic exchange is potentially beneficial to bacterial hosts, but there are also potential costs, which may be considerable in the case of phage infection. Some bacterial resistance mechanisms target both beneficial and deleterious forms of genetic exchange. Using a general epidemiological model, we explored under which conditions such resistance mechanisms may evolve. We considered a population of hosts that may be infected by FGEs that either confer a benefit or are deleterious to host fitness, and we analysed the epidemiological and evolutionary outcomes of resistance evolving under different cost/benefit scenarios. We show that the degree of co-infection between these two types of infection is particularly important in determining the evolutionarily stable level of host resistance. We explore these results using the example of CRISPR-Cas, a form of bacterial immunity that targets a variety of FGEs, and we show the potential role of bacteriophage infection in selecting for resistance mechanisms that in turn limit the acquisition of plasmid-borne antibiotic resistance. Finally, beyond microbes, we discuss how endosymbiotic associations may have shaped the evolution of host immune responses to pathogens.