UCLA

Strongyloides stercoralis is a human-parasitic gastrointestinal nematode that infects up to 610 million people worldwide. S. stercoralis infective third-stage larvae (iL3s) actively search for hosts to infect, and then invade hosts by penetrating directly through host skin. While the host-seeking behaviors of iL3s are becoming increasingly well-understood, remarkably little is known about skin-penetration behavior. We do not yet know what host- or parasitic-specific factors regulate skin penetration and its composite behaviors, nor do we know what biochemical mechanisms are responsible. We found that S. ratti iL3s progressively penetrate the skin of a rat host within 10 minutes. S. stercoralis iL3s also progressively penetrate rat (non-host) skin over the course of 10 minutes, but with reduced efficiency. Comparing skin-penetration behavior on skin from different rodents revealed that S. ratti iL3s engage in preferential penetration of rat (host) skin. We observed no changes in the efficiency of skin-penetration behavior depending on the sex of the host or the time during the infection cycle when the iL3s emerged from the host; however, younger iL3s penetrate more efficiently than older iL3s. In addition, we found that S. stercoralis and S. ratti iL3s engage in complex behavioral sequences during skin-penetration. We observed cycles of puncture, extrication, completion, and re-emergence events, with re-emergence events occurring specifically on non-host skin. We also performed a bioinformatics analysis of a family of genes that has previously been implicated in the process of skin penetration, the astacin metalloprotease genes. By analyzing publicly available RNA-sequencing data and performing a phylogenetic analysis of the astacin genes, we identified astacin genes that are highly expressed in iL3s and differentially expressed in iL3s relative to other life stages. A phylogenetic comparison of the astacin genes of S. ratti, S. stercoralis, and the free-living nematode Caenorhabditis elegans revealed that these genes are found in parasite-specific expansions of the astacin gene families. We found that some astacin genes are expressed in the iL3 pharynx, suggesting that they may be secreted through the pharynx during skin penetration. Together, our results identify behavioral and biochemical mechanisms that drive skin-penetration behavior.