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News: Beyond pest control: What can we learn from parasites?
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Parasites are infamous for exploiting other organisms for food, they are often treated as pests and pathogens with the narrow focus to get rid of them. Sea lice are no exception as major blood-feeding ectoparasites of farmed and wild fish. But can parasites help us to understand basic physiological mechanisms, like uptake of nutrients? It is quite astonishing how little is known about how the very common relationship of host and parasite actually works on the molecular level.

In our new study in Scientific Reports (Heggland et al., 2019) on the Atlantic salmon louse (Lepeophtheirus salmonis), we combine in silico, in vivo, and in vitro evidence, to shed light on a long-standing mystery of physiology that could potentially even affect biomedical research: intestinal heme absorption in the parasite. Heme is an essential iron containing co-factor of many essential proteins in aerobic organisms, with hemoglobin possibly the most well-known one. It is also the most bioavailable source of iron for humans.

Heme is one of the most versatile bio-molecules besides carbohydrates, nucleotides, lipids, and amino acids. However, using pathway analysis of our parasite, we discovered that the salmon louse is lacking most of the genes of the pathway for heme synthesis. This pathway is highly conserved throughout evolution. The loss of the heme synthesis pathway is maybe not as surprising for a blood feeding organism with nearly unlimited access to heme. But then new questions arise: how does the parasite extract heme from host blood, how is it transported through the cells, and further passed on to the other cells?

It has been long known that other organisms, including mammals, take up heme from food in their intestine by various mechanisms. One example is the family of HRG proteins in C. elegans that is also a heme auxotroph, but some of these genes are only present in nematodes, hinting at that there might be different mechanisms at work in different organisms. Using computational methods, we proposed that heme uptake could also be mediated by a different and very common class of proteins, the class B scavenger receptors (SCARB). SCARB proteins have a very wide range of ligands like lipids and oxidized lipoproteins, and we proposed that heme just might have been overlooked as a possible ligand. Our specific candidate LsHSCARB (gene id: EMLSAG00000005382, protein id: EMLSAP00000005382) is also one of the most highly expressed genes in the intestine. The protein was then further characterized by RNA-interference mediated knock-down, and we showed that it is also a heme-binder.

We think that our paper is a good example of a well-working collaboration between computational and molecular biologists that contributes to a better understanding of life.


A scavenger receptor B (CD36)-like protein is a potential mediator of intestinal heme absorption in the hematophagous ectoparasite Lepeophtheirus salmonis

Erna Irene Heggland, Christiane Eichner, Svein Isungset Støve, Aurora Martinez, Frank Nilsen and Michael Dondrup Scientific Reports 9(1): 4218 (2019)

Intestinal absorption of heme has remained enigmatic for years, even though heme provides the most bioavailable form of iron. The salmon louse, Lepeophtheirus salmonis, is a heme auxotrophic ectoparasite feeding on large quantities of blood from its host, the salmon. Here we show that a scavenging CD36-like receptor is a potential mediator of heme absorption in the intestine of the salmon louse. The receptor was characterized by a heme binding assay using recombinantly expressed protein, in situ hybridization and immunohistochemistry, as well as functional knockdown studies in the louse. A computational structural model of the receptor predicted a binding pocket for heme, as also supported by in silico docking. The mRNA and protein were expressed exclusively in the intestine of the louse. Further, knocking down the transcript resulted in lower heme levels in the adult female louse, production of shorter egg strings, and an overall lower hatching success of the eggs. Finally, starving the lice caused the transcript expression of the receptor to decrease. To our knowledge, this is the first time a CD36-like protein has been suggested to be an intestinal heme receptor.

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@Michael: Bit confused about the title you are using here. Are the parasites benefiting salmon in any way (they seem to benefit humans by providing a continuous low level stimulation to the immune system)?

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genomax
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Hi genomax, what I meant was that they help us understand some biological process and as a contrast to most people viewing them as a problem. In fact, I think they could be a good model for heme trafficking. With respect to any benefit to the fish, we haven't seen a lot of evidence for this yet, but speculation is that there were other more severe threats from microbes and that therefore Atlantic salmon does not spend energy for removing ectoparasites, while other salmonids readily overcome sea lice infections.

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Michael Dondrup
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Surely parasites e.g. in part keep populations at check. I found the title offending as hell..

ADD REPLYlink 11 months ago
5heikki
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How about this? Are parasites good as model organisms? I am honestly not so much invested in the biostars post title, it sounded catchy to me. This page seems to describe nicely what I wanted to say "In praise of parasites": https://www.smithsonianmag.com/science-nature/praise-parasites-180971139/

ADD REPLYlink 11 months ago
Michael Dondrup
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Much better. Catchy, yes, but also misleading, enforcing negative stereotypes etc.

-resident sjw

ADD REPLYlink 11 months ago
5heikki
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I haven't seen the original title but I will say that we can definitely learn a lot from parasites when it comes to the function of cells. Then what we learn could be put to good use.

I think the title should reflect that message: what can we learn from parasites, or what are parasites good for etc

I don't think that parasites are good model organisms. They are usually very specific to one particular niche - and what you learn from one parasite will not translate to another organism - that's how I would define a "model" organism.

ADD REPLYlink 11 months ago
Istvan Albert
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Hi Istvan,

I think "what can we learn from parasites" really is the best way of saying it, "In praise of parasites" would be another if it hadn't been taken already. Thanks for your suggestion.

ADD REPLYlink 11 months ago
Michael Dondrup
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