Abstract
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.
Highlights
Parasitic nematodes comprise a major group of pathogens that infect nearly one third of the human population, and compromise, or threaten, the health and productivity of most agricultural animals and plants throughout the world
To relate the intestinal cell proteins expressed from the core species (T. suis, A. suum and H. contortus) to proteins from other nematode species, we established a database of deduced proteomes of 15 eukaryotic species
The 248,475 proteins across all of the species formed 31,014 orthologous protein families (OrtFams; Fig. 2; Table S1) that were phylogenetically categorized based on species representation (Fig. 2, Group c; Table S2)
Summary
Parasitic nematodes comprise a major group of pathogens that infect nearly one third of the human population, and compromise, or threaten, the health and productivity of most agricultural animals and plants throughout the world. The selection of anthelmintics (nematicides) that can be used for treatment and control of these pathogens is relatively limited, and acquired resistance to anthelmintics by parasitic nematodes is a growing problem (Albonico et al, 2004; Awadzi et al, 2004; Bourguinat et al, 2008; Osei-Atweneboana et al, 2007; Vercruysse et al, 2012). The intestine has a relatively simple tubular design formed by a single cell layer of intestinal cells that resemble polarized epithelial cells (Yin et al, 2008). This single cell layer serves as a physical separation between the environment and
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