Omics Driven Understanding of the Intestines of Parasitic Nematodes

Abstract

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. Multiomics data were generated to uncover the evolutionary principles underlying both conserved and adaptable features of the nematode intestine. Whole genomes were used to reveal the functional potential of the nematodes, tissue-specific transcriptomes provided a deep assessment of genes that are expressed in the adult nematode intestine, and comparison of selected core species was used to determine a first approximation of the pan-Nematoda intestinal transcriptome. Differentially expressed transcripts were also identified among intestinal regions, with the largest number expressed at significantly higher levels in the anterior region, identifying this region as the most functionally unique compared to middle and posterior regions. Profiling intestinal miRNAs targeting these genes identified the conserved intestinal miRNAs. Proteomics of intestinal cell compartments assigned proteins to several different intestinal cell compartments (intestinal tissue, the integral and peripheral intestinal membranes, and the intestinal lumen). Finally, advanced bioinformatic approaches were used to predict intestinal cell functional categories of seminal importance to parasite survival, which can now be experimentally tested and validated. The data provide the most comprehensive compilation of constitutively and differentially expressed genes, predicted gene regulators, and proteins of the nematode intestine. The information provides knowledge that is essential to understand molecular features of nematode intestinal cells and functions of fundamental importance to the intestine of many, if not all, parasitic nematodes.

Rapid determination of nematode cell and organ susceptibility to toxic treatments

“…As one example, our research has focused on the nematode intestine due to its apparent hypersensitivity to some anthelmintics and because it has relative tractability to experimental approaches compared to other tissues ( Jasmer et al, 2019 ). In recent progress ( Jasmer et al, 2020 ), we identified a set of nematode intestinal toxins/toxicants (NITs) that caused apparent irreparable intestinal cell damage in A. suum L3 and L4.…”

Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses

“…Intestinal helminth infections are common in man and animals, especially in developing regions of Africa, Asia and the Americas [1][2][3]. These parasitic infections generate substantial mortality and morbidity and produce relevant physical and mental disorders and often persist in the face of serious economic problems [2].…”

“…These parasitic infections generate substantial mortality and morbidity and produce relevant physical and mental disorders and often persist in the face of serious economic problems [2]. Moreover, infections by intestinal helminths also compromise the health and productivity of livestock worldwide [3]. Currently, the impact of intestinal helminth infections only can be reduced by anthelminthic treatment, but the progressive emergence of resistances to these drugs limits their utility.…”

Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses

“…Intestinal helminth infections are common in man and animals, especially in developing regions of Africa, Asia and the Americas [1][2][3]. These parasitic infections generate substantial morbidity and produce relevant physical and mental disorders and often persist in the face of serious economic problems [2].…”

“…Moreover, infections by intestinal helminths also compromise the health and productivity of livestock worldwide [3]. Currently, the impact of intestinal helminth infections mainly can be reduced by anthelminthic treatment, but the progressive emergence of resistances to these drugs limits their utility.…”