Pan-Nematoda Transcriptomic Elucidation of Essential Intestinal Functions and Therapeutic Targets With Broad Potential

• The intestine is an ideal target for therapeutics to control parasitic nematodes.
• This is a pioneering pan-phylum study of the intestinal transcriptome/proteome in the Nematoda.
• Conserved intestinal cell functions were delineated for the phylum clades and species of nematodes.
• The possibility for selective targeting for therapeutic purposes is discussed.Using multi-omic data integration and evolutionary considerations, we derived a natural history of births, deaths and variation in family members for over 10,000 intestinal protein families conserved among ten nematode species. The development of therapeutics is explored in relation to conserved intestinal cell functions and molecular features specific to the parasite proteins.

The nematode intestine is continuous with the outside environment, making it easily accessible to anthelmintics for parasite control, but the development of new therapeutics is impeded by limited knowledge of nematode intestinal cell biology. We established the most comprehensive nematode intestinal functional database to date by generating transcriptional data from the dissected intestines of three parasitic nematodes spanning the phylum, and integrating the results with the whole proteomes of 10 nematodes (including 9 pathogens of humans or animals) and 3 host species and 2 outgroup species. We resolved 10,772 predicted nematode intestinal protein families (IntFams), and studied their presence and absence within the different lineages (births and deaths) among nematodes. Conserved intestinal cell functions representing ancestral functions of evolutionary importance were delineated, and molecular features useful for selective therapeutic targeting were identified. Molecular patterns conserved among IntFam proteins demonstrated large potential as therapeutic targets to inhibit intestinal cell functions with broad applications towards treatment and control of parasitic nematodes.