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.