Co-evolutionary dynamics between a defensive microbe and a pathogen driven by fluctuating selection

Microbes that protect their hosts from pathogenic infection are widespread components of the microbiota of both plants and animals. It has been found that interactions between 'defensive' microbes and pathogens can be genotype-specific and even underlie the variation in host resistance to pathogenic infection. These observations suggest a dynamic co-evolutionary association between pathogens and defensive microbes, but direct evidence of co-evolution is lacking. We tested the hypothesis that defensive microbes and pathogens could co-evolve within host populations by co-passaging a microbe with host-defensive properties (Enterococcus faecalis) and a pathogen (Staphylococcus aureus) within Caenorhabditis elegans nematodes. Using both phenotypic and genomic analyses across evolutionary time, we found patterns of pathogen local adaptation and defensive microbe-pathogen co-evolution via fluctuating selection dynamics. Moreover, co-evolution with defensive microbes resulted in more rapid and divergent pathogen evolution compared to pathogens evolved independently in host populations. Taken together, our results indicate the potential for defensive microbes and pathogens to co-evolve, driving interaction specificity and pathogen evolutionary divergence in the absence of host evolution.