Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes

Significance Skin-penetrating nematodes are a major cause of morbidity worldwide. The infective larvae of these parasites actively search for humans to infect, but how they do this is poorly understood. We show that infective larvae have chemosensory preferences that are distinct from those of noninfective adults, which may ensure that only infective larvae host seek. We find that human-parasitic hookworms and threadworms have highly divergent chemosensory behaviors, suggesting they may use distinct strategies for finding and infecting humans. Finally, we show that the S. stercoralis tax-4 gene is required for attraction to a human-emitted odorant and in-host development. Our results suggest that chemosensory pathways mediated by Ss-tax-4 are important for the ability of infective larvae to find and infect human hosts.