Pan-Nematoda Transcriptomic Elucidation of Essential Intestinal Functions and Therapeutic Targets With Broad Potential.
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.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Qi
Q
Wang
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Bruce A
BA
Rosa
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA.
Douglas P
DP
Jasmer
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA ; Division of Infectious Disease, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Makedonka
M
Mitreva
D000595:Amino Acid Sequence; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D017124:Conserved Sequence; D005260:Female; D020440:Gene Duplication / Q000187:drug effects; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009348:Nematoda / Q000235:genetics*; D010271:Parasites / Q000187:drug effects; D010802:Phylogeny; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D034421:Sus scrofa; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
D000871:Anthelmintics; D020543:Proteome
Intestinal protein families; Molecular functions; Nematode intestine; Therapeutic targets