Coria, A. L. | Search bioRxiv

bioRxiv2024

Evidence of opportunistic blood feeding in the parasitic nematode Heligmosomoides bakeri

Haem, which binds iron and oxygen, is essential for parasitic nematode growth. Nematodes lack endogenous haem synthesis pathways and acquire haem from their environment or intracellular symbionts. Genes involved in haem degradation and detoxification have been identified in parasitic nematodes who are either specialised blood feeders (haematophages) or reside in the blood stream. Targeting these genes, so limiting parasite growth and promoting parasite death, provides a new therapeutic avenue against blood feeding parasitic nematodes. Heligmosomoides bakeri, a model intestinal parasitic nematode, has not been considered a blood feeder. Adults live in the intestinal lumen and graze on host tissue. However, the earlier larval stages enter the intestinal tissue, where they grow and moult multiple times, an oxygen demanding process. We have shown that, in vivo, likely through nematode-induced damage, many tissue-dwelling H. bakeri are in close vicinity of red blood cells. During this time, infection induces host anemia. Further, tissue-dwelling H. bakeri that have fed on blood have an increased expression of collagen genes compared to those parasites that had not fed on blood. In vitro, this translates to a growth advantage. Our findings suggest blood feeding is more widespread among nematodes than currently described. We argue that biochemical adaptations previously considered to be limited to blood-feeders are found in other nematodes. Moreover, H. bakeri can serve as a model for studying blood-feeding mechanisms and developing anthelminthic strategies to them.

zoology↗

bioRxiv2022

Transcriptional patterns of sexual dimorphism and host developmental programs in the model parasitic nematode Heligmosomoides polygyrus

Heligmosomoides bakeri (often mistaken for Heligmosomoides polygyrus) is a promising model for parasitic nematodes with the key advantage of being amenable to study and manipulation within a controlled laboratory environment. While draft genome sequences are available for this worm, which allow for comparative genomic analyses between nematodes, there is a notable lack of information on its gene expression. Here, we have generated biologically replicated RNA-seq datasets from samples taken throughout the parasitic life of H. bakeri. We find extensive transcriptional sexual dimorphism throughout the fourth larval and adult stages of this parasite and identify alternative splicing, glycosylation, and ubiquitination as particularly important processes for establishing and/or maintaining sex-specific gene expression in this species. Further, we find sex-linked differences in transcription related to aging and oxidative and osmotic stress responses. Additionally, we observe a starvation-like signature among transcripts whose expression is consistently up-regulated in males, which may reflect a higher energy expenditure by male worms. We detect evidence of increased importance for anaerobic respiration among the adult worms, which coincides with the parasites migration into the physiologically hypoxic environment of the intestinal lumen. Further, we hypothesize that oxygen concentration may be an important driver of the worms encysting in the intestinal mucosa as larvae, which not only fully exposes the worms to their hosts immune system, but also shapes many of the interactions between the host and parasite. We find stage- and sex-specific variation in the expression of immunomodulatory genes and in anthelmintic targets. In addition to generating new hypotheses for follow-up experiments into the worms behaviour, physiology, and metabolism, our datasets enable future more in-depth comparisons between nematodes to better define the utility of H. bakeri as a model for parasitic nematodes in general. Author SummaryParasitic nematodes (roundworms) that infect humans and livestock are a major health and economic burden but are challenging to study in a laboratory environment because of their required hosts. One strategy to get around this difficulty is to first study a rodent model to guide targeted experiments in the more difficult study system. Heligmosomoides bakeri is closely related to the nematode parasites of humans and livestock and naturally parasitizes mice. We have generated information on the expression of all the genes in this worm throughout the stages of its life when it is parasitic. This information allows us to examine how different the male and female worms are at the molecular level. We also describe major developmental events that occur in the worm, which extend our understanding of the interactions between this parasite and its host. We analyse the expression of genes known to be involved in interfering with host immune responses and others known to be targeted by drugs designed to kill worms. This new information will allow for better comparisons among nematodes to assess how well this rodent model system works for studying parasitic nematodes in general.

genomics↗