High-throughput phenotyping of infection by diverse microsporidia species reveals a wild C. elegans strain with opposing resistance and susceptibility traits.

Animals are under constant selective pressure from a myriad of diverse pathogens. Microsporidia are ubiquitous animal parasites, but the influence they exert on shaping animal genomes is mostly unknown. Using multiplexed competition assays, we measured the impact of four different species of microsporidia on 22 wild isolates of Caenorhabditis elegans. This resulted in the identification and confirmation of 13 strains with significantly altered population fitness profiles under infection conditions. One of these identified strains, JU1400, is sensitive to an epidermal-infecting species by lacking tolerance to infection. JU1400 is also resistant to an intestinal-infecting species and can specifically recognize and destroy this pathogen. Genetic mapping of JU1400 demonstrates that these two opposing phenotypes are caused by separate loci. Transcriptional analysis reveals the JU1400 sensitivity to epidermal microsporidia infection results in a response pattern that shares similarity to toxin-induced responses. In contrast, we do not observe JU1400 intestinal resistance being regulated at the transcriptional level. The transcriptional response to these four microsporidia species is conserved, with C. elegans strain-specific differences in potential immune genes. Together, our results show that phenotypic differences to microsporidia infection amongst C. elegans are common and that animals can evolve species-specific genetic interactions. Author summary: Animals display a large diversity of different characteristics within a population. One characteristic that varies within populations is susceptibility to infectious disease. Microsporidia are ubiquitous animal parasites that infect most types of animals, but the influence that these parasites have had on animal evolution and diversity is not well understood. Using wild isolates of the model organism Caenorhabditis elegans, we tested the diversity of responses to infection by four naturally occurring microsporidia species. These experiments were done with a pooled assay that allowed for the determination of the relative abundance of strains within a population under different infection conditions. These experiments identified a C. elegans strain that is sensitive to infection by one species of microsporidia but resistant to another. Genetic mapping experiments show that different genetic regions are responsible for these different infection responses. Together our study demonstrates that there is variability in the susceptibility of C. elegans to microsporidia infection and suggests that these parasites have likely had a large influence on animal evolution. [ABSTRACT FROM AUTHOR]