Natural Genetic Variation in the Caenorhabditis elegans Response to Pseudomonas aeruginosa

Caenorhabditis elegans responds to pathogenic microorganisms by activating its innate immune system, which consists of physical barriers, behavioral responses, and microbial killing mechanisms. We examined whether natural variation plays a role in the response of C. elegans to Pseudomonas aeruginosa using two C. elegans strains that carry the same allele of npr-1, a gene that encodes a G-protein-coupled receptor related to mammalian neuropeptide Y receptors, but that differ in their genetic backgrounds. Strains carrying an allele for the NPR-1 215F isoform have been shown to exhibit lack of pathogen avoidance behavior and deficient immune response toward P. aeruginosa relative to the wild-type (N2) strain. We found that the wild isolate from Germany RC301, which carries the allele for NPR-1 215F, shows an enhanced resistance to P. aeruginosa infection when compared with strain DA650, which also carries NPR-1 215F but in an N2 background. Using a whole-genome sequencing single-nucleotide polymorphism (WGS-SNP) mapping strategy, we determined that the resistance to P. aeruginosa infection maps to a region on chromosome V. Furthermore, we demonstrated that the mechanism for the enhanced resistance to P. aeruginosa infection relies exclusively on strong P. aeruginosa avoidance behavior, and does not involve the main immune, stress, and lifespan extension pathways in C. elegans. Our findings underscore the importance of pathogen-specific behavioral immune defense in the wild, which seems to be favored over the more energy-costly mechanism of activation of physiological cellular defenses.