Host defense mechanisms induce genome instability in an opportunistic fungal pathogen

The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogenCandida albicansfrequently undergoes large-scale genomic changes, including aneuploidy and loss-of heterozygosity (LOH), following exposure to physiological stressors and host environments. However, the specific host factors that induceC. albicansgenome instability remains largely unknown. Here, we leveraged genetically-tractable nematode hosts to specifically investigate the innate immune components driving host-associatedC. albicansgenome instability, which include host production of antimicrobial peptides (AMPs) and reactive oxygen species (ROS).C. albicansassociated with wildtype, immunocompetent hosts carried multiple large-scale genomic changes including LOH, whole chromosome, and segmental aneuploidies. In contrast,C. albicansassociated with immunocompromised hosts deficient in AMPs or ROS production had reduced LOH frequencies and fewer, if any, additional genomic changes. We also found thatC. albicans cap1Δ/Δ strains deficient in ROS detoxification, were more susceptible to host-produced ROS genome instability compared to wildtypeC. albicans. Further, genomic perturbations resulting from host-produced ROS are mitigated by the addition of antioxidants. Taken together, this work suggests that host-produced ROS and AMPs induces genotypic plasticity inC. albicanswhich may facilitate rapid adaptation and lead to phenotypic changes.