Genetic and functional diversification of chemosensory pathway receptors in mosquito-borne filarial nematodes

• DOI: 10.1371/journal.pbio.3000723
• Publication Date: 2020-06-08T17:33:31Z
• Authors: Nicolas J. Wheeler; Zachary W. Heimark; Paul M. Airs; Alexis Mann; Lyric C. Bartholomay; Mostafa Zamanian
• Keywords: Life Cycle Stages; Genome; QH301-705.5; Chemotaxis; Temperature; Genetic Variation; TRPV Cation Channels; Helminth Proteins; Chemoreceptor Cells; 3. Good health; Culicidae; Elephantiasis, Filarial; Larva; Animals; RNA Interference; Biology (General); Caenorhabditis elegans; Brugia malayi; Research Article; RNA, Double-Stranded

AbstractLymphatic filariasis (LF) afflicts over 60 million people worldwide and leads to severe pathological outcomes in chronic cases. The nematode parasites (Nematoda: Filarioidea) that cause LF require both arthropod (mosquito) intermediate hosts and mammalian definitive hosts for their propagation. The invasion and migration of filarial worms through host tissues are complex and critical to survival, yet little is known about the receptors and signaling pathways that mediate directed migration in these medically important species. In order to better understand the role of chemosensory signaling in filarial worm taxis, we employ comparative genomics, transcriptomics, reverse genetics, and chemical approaches to identify putative chemosensory receptor proteins and perturb chemotaxis phenotypes in filarial worms. We find that chemoreceptor family size is correlated with the presence of environmental (extra-host) stages in nematode life cycles, and that filarial worms contain a compact and highly-diverged chemoreceptor complement and lineage-specific ion channels that are predicted to operate downstream of chemoreceptor activation. InBrugia malayi, an etiological agent of LF, chemoreceptor expression patterns correspond to distinct parasite migration events across the life cycle. To interrogate the role of chemosensation in the migration of larval worms, arthropod infectious stage (microfilariae) and mammalian infectious stage (L3)Brugiaparasites were incubated in nicotinamide, an agonist of the nematode transient receptor potential (TRP) channel OSM-9. Exposure of microfilariae to nicotinamide alters intra-mosquito migration while exposure of L3s reduces chemotaxis towards host-associated cuesin vitro. Nicotinamide also potently modulates thermosensory responses in L3s, suggesting a polymodal sensory role forBrugia osm-9. Reverse genetic studies implicate bothBrugia osm-9and the cyclic nucleotide-gated (CNG) channel subunittax-4in larval chemotaxis towards host serum, and these ion channel subunits rescue sensory defects inC. elegans osm-9andtax-4knock-out strains. Together, these data reveal genetic and functional diversification of chemosensory signaling proteins in filarial worms, and encourage a more thorough investigation of clade and parasite-specific facets of nematode sensory receptor biology.