Presentation Details
Don Tucker Finalist: Human-associated odorants drive host invasion in the human-infective nematode Strongyloides stercoralis

Damia Akimori1, 2, Elissa Hallem1.

1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.2Molecular Biology Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, CA, USA

Abstract


Over 610 million individuals globally are infected with the skin-penetrating gastrointestinal parasitic nematode Strongyloides stercoralis. S. stercoralis infects hosts as developmentally arrested infective third-stage larvae (iL3). iL3s navigate through the soil searching for hosts in a process that involves attraction to host-associated odorants. They then invade hosts by burrowing through the skin. We have identified human-associated odorants that stimulate the skin-penetration behaviors of S. stercoralis iL3s. The responses to these odorants are species-specific – they do not stimulate skin penetration in the closely related rat-parasitic nematode Strongyloides ratti. We are now investigating the neural and molecular mechanisms that underlie these responses. Large families of G protein-coupled receptors encode odorant receptors (ORs) in nematodes and have been thoroughly identified in the model nematode Caenorhabditis elegans. We verified and manually curated putative OR genes in S. stercoralis. Through transcriptional analysis of differential gene expression between iL3s and free-living life stages of S. stercoralis, we identified several OR genes that are highly expressed and upregulated in iL3. Fluorescent reporter constructs using the promoters for these OR genes revealed expression in specific subsets of head sensory neurons, enabling us to genetically target putative olfactory neurons for the first time. We are now testing the requirement for these neurons during skin penetration using chemogenetic silencing and examining their activity using calcium imaging. We are also investigating the requirement for individual OR genes using CRISPR. Together, these experiments are providing insight into how skin-penetrating nematodes invade human hosts, with broad implications for nematode control.

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