Using newly optimized genetic tools to probe Strongyloides sensory behaviors

Abstract

The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and economic burden upon marginalized communities. While current chemotherapies treat strongyloidiasis, disease recrudescence and the looming threat of anthelminthic resistance necessitate novel strategies for nematode control. Throughout its life cycle, S. stercoralis relies upon sensory cues to aid in environmental navigation and coordinate developmental progression. Odorants, tastants, gases, and temperature have been shown to shape parasite behaviors that drive host seeking and infectivity; however, many of these sensory behaviors remain poorly understood, and their underlying molecular and neural mechanisms are largely uncharacterized. Disruption of sensory circuits essential to parasitism presents a promising strategy for future interventions. In this review, we describe our current understanding of sensory behaviors – namely olfactory, gustatory, gas sensing, and thermosensory behaviors – in Strongyloides spp. We also highlight the ever-growing cache of genetic tools optimized for use in Strongyloides that have facilitated these findings, including transgenesis, CRISPR/Cas9-mediated mutagenesis, RNAi, chemogenetic neuronal silencing, and the use of fluorescent biosensors to measure neuronal activity. Bolstered by these tools, we are poised to enter an era of rapid discovery in Strongyloides sensory neurobiology, which has the potential to shape pioneering advances in the prevention and treatment of strongyloidiasis.