Adaptation to oral infection in D. melanogaster through evolution of both resistance and disease tolerance mechanisms

Pathogens exert strong selection on hosts, that evolve and deploy different defensive strategies, namely minimizing pathogen exposure (avoidance), directly promoting pathogen elimination (resistance), and/or managing the deleterious effects of illness (disease tolerance). However, how the response to pathogens partitions across these processes has never been directly assessed in a single system, let alone in the context of known adaptive trajectories under controlled selection regimes. Here, an experimental evolution system composed of D. melanogaster and its natural pathogen P. entomophila is used to independently assess the role of behavioural traits, and of resistance and disease tolerance mechanisms on host evolution. We compare one replicate of a population adapted to oral infection with P. entomophila (BactOral) to a replicate of its control population to find no evidence for behavioural change but measurable differences in both resistance and disease tolerance. In BactOral, we identify a relative decrease in bacterial loads correlated with an increase in gut production of specific AMPs, but no differences in bacterial intake, in gut cell renewal rate, or in the rate of bacterial defecation, pointing to a strengthening in resistance. Additionally, we posit that disease tolerance also contributes to the adaptive response of the BactOral population through a tighter control of its immune response and of the deleterious effects of exposure. This study reveals a genetically complex and mechanistically multi-layered response, possibly reflecting the structure of adaptation to infection in natural populations.