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Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2023)

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.

    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2024)
    Skin-penetrating nematodes, including the human threadworm Strongyloides stercoralis and hookworms in the genera Necator and Ancylostoma, are gastrointestinal parasites that are a major cause of neglected tropical disease in low-resource settings worldwide. These parasites infect hosts as soil-dwelling infective larvae that navigate towards hosts using host-emitted sensory cues such as odorants and body heat. Upon host contact, they invade the host by penetrating through the skin. The process of skin penetration is critical for successful parasitism but remains poorly understood and understudied. Here, we review current knowledge of skin-penetration behaviour and its underlying mechanisms in the human parasite S. stercoralis, the closely related rat parasite Strongyloides ratti, and other skin-penetrating nematodes such as hookworms. We also highlight important directions for future investigations into this underexplored process and discuss how recent advances in molecular genetic and genomic tools for Strongyloides species will enable mechanistic investigations of skin penetration and other essential parasitic behaviours in future studies. This article is part of the Theo Murphy meeting issue Strongyloides: omics to worm-free populations.
      Cover page: Invade or die: behaviours and biochemical mechanisms that drive skin penetration in Strongyloides and other skin-penetrating nematodes.
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