Evolution of resistance and disease tolerance mechanisms to oral bacterial infection in <i>Drosophila melanogaster</i>

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 host response partitions across these processes has not been directly tested in a single host-pathogen system, let alone in the context of known adaptive trajectories resulting from experimental evolution. Here, we compare a <i>Drosophila melanogaster</i> population adapted to oral infection with its natural pathogen <i>Pseudomonas entomophila</i> (BactOral), to its control population to find no evidence for behavioural changes but measurable differences in both resistance and disease tolerance. In BactOral, no differences were detected in bacterial intake or defecation, nor gut cell renewal. However, a measurable relative decrease in bacterial loads correlates with an increase in gut-specific anti-microbial peptide production, pointing to a strengthening in resistance. Additionally, we posit that disease tolerance also contributes to the response of BactOral through a tighter control of self- and pathogen-derived damage caused by bacteria exposure. This study reveals a genetically complex and mechanistically multi-layered response, possibly reflecting the structure of adaptation to infection in natural populations.