Intestinal cell diversity and treatment responses in a parasitic nematode at single cell resolution.

Background: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems.

Cell Death and Transcriptional Responses Induced in Larvae of the Nematode by Toxins/Toxicants with Broad Phylogenetic Efficacy.

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in to , a phylogenetically distant parasitic nematode of significance for both human and agricultural animal health. We utilized a diverse group of small molecule inhibitors referred to as nematode intestinal toxins/toxicants (NITs) coupled with motility, cytological and cell death assays to resolve gross effects on motility and individual cells and organ systems of two larval stages in culture.

Rapid determination of nematode cell and organ susceptibility to toxic treatments.

In research focused on the intestine of parasitic nematodes, we recently identified small molecule inhibitors toxic to intestinal cells of larval Ascaris suum (nematode intestinal toxins/toxicants; "NITs"). Some NITs had anthelmintic activity across the phylogenetic diversity of the Nematoda. The whole-worm motility inhibition assay quantified anthelmintic activity, but worm responses to NITs in relation to pathology or affected molecular pathways was not acquired.

De novo identification of toxicants that cause irreparable damage to parasitic nematode intestinal cells.

Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based on de novo computational target prioritization of the 3,564 conserved intestine genes in A.

Omics Driven Understanding of the Intestines of Parasitic Nematodes.

The biological and molecular complexity of nematodes has impeded research on development of new therapies for treatment and control. We have focused on the versatility of the nematode intestine as a target for new therapies. To that end, it is desirable to establish a broad and deep understanding of the molecular architecture underlying intestinal cell functions at the pan-Nematoda level.