title: Functional and phylogenetic characterization of proteins detected in various nematode intestinal compartments.
abstract: The parasitic nematode intestine is responsible for nutrient digestion and absorption, and many other processes essential for reproduction and survival, making it a valuable target for anthelmintic drug treatment. However, nematodes display extreme biological diversity (including occupying distinct trophic habitats), resulting in limited knowledge of intestinal cell/protein functions of fundamental or adaptive significance. We developed a perfusion model for isolating intestinal proteins in Ascaris suum (a parasite of humans and swine), allowing for the identification of over 1000 intestinal A. suum proteins (using mass spectrometry), which were assigned to several different intestinal cell compartments (intestinal tissue, the integral and peripheral intestinal membranes, and the intestinal lumen). A multi-omics analysis approach identified a large diversity of biological functions across intestinal compartments, based on both functional enrichment analysis (identifying terms related to detoxification, proteolysis, and host-parasite interactions) and regulatory binding sequence analysis to identify putatively active compartment-specific transcription factors (identifying many related to intestinal sex differentiation or lifespan regulation). Orthologs of A. suum proteins in 15 other nematodes species, five host species, and two outgroups were identified and analyzed. Different cellular compartments demonstrated markedly different levels of protein conservation; e.g. integral intestinal membrane proteins were the most conserved among nematodes (up to 96% conservation), whereas intestinal lumen proteins were the most diverse (only 6% conservation across all nematodes, and 71% with no host orthologs). Finally, this integrated multi-omics analysis identified conserved nematode-specific intestinal proteins likely performing essential functions (including V-type ATPases and ABC transporters), which may serve as promising anthelmintic drug or vaccine targets in future research. Collectively, the findings provide valuable new insights on conserved and adaptive features of nematode intestinal cells, membranes and the intestinal lumen, and potential targets for parasite treatment and control.
authors.affiliation: From the ‡The Genome Institute, Washington University in St Louis, Missouri 63108;
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rosa
authors.affiliation: §Department of Cell Biology & Physiology and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63108;
authors.forename: Reid
authors.initials: R
authors.lastname: Townsend
authors.affiliation: ¶Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164;
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Jasmer
authors.affiliation: From the ‡The Genome Institute, Washington University in St Louis, Missouri 63108; ‖Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108 mmitreva@genome.wustl.edu.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
mesh_terms: D000818:Animals; D017165:Ascaris suum / Q000378:metabolism*; D001483:Base Sequence; D017124:Conserved Sequence; D005260:Female; D005786:Gene Expression Regulation; D063990:Gene Ontology; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006790:Host-Parasite Interactions; D007413:Intestinal Mucosa / Q000378:metabolism*; D007526:Isoelectric Point; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009928:Organ Specificity; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D040901:Proteomics; D034421:Sus scrofa; D014158:Transcription, Genetic
chemical_list: D015801:Helminth Proteins