Schistosoma mansoni does not and cannot oxidise fatty acids, but these are used for biosynthetic purposes instead

Abstract

Adult schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, have always been considered to be homolactic fermenters and in their energy metabolism strictly dependent on carbohydrates. However, more recent studies suggested that fatty acid β-oxidation is essential for egg production by adult female Schistosoma mansoni. To address this conundrum, we performed a comprehensive study on the lipid metabolism of S. mansoni. Incubations with [ 14 C]-labelled fatty acids demonstrated that adults, eggs and miracidia of S. mansoni did not oxidize fatty acids, as no 14 CO 2 production could be detected. We then re-examined the S. mansoni genome using the genes known to be involved in fatty acid oxidation in six eukaryotic model reference species. This showed that the earlier automatically annotated genes for fatty acid oxidation were in fact incorrectly annotated. In a further analysis we could not detect any genes encoding β-oxidation enzymes, which demonstrates that S. mansoni cannot use this pathway in any of its lifecycle stages. The same was true for S. japonicum.Absence of β-oxidation, however, does not imply that fatty acids from the host are not metabolized by schistosomes. Adult schistosomes can use and modify fatty acids from their host for biosynthetic purposes and incorporate them in phospholipids and neutral lipids. Female worms deposit large amounts of these lipids in the eggs they produce, which explains why interference with the lipid metabolism in females will disturb egg formation, even though fatty acid β-oxidation does not occur in schistosomes. Our analyses of S. mansoni further revealed that during the development and maturation of the miracidium inside the egg, changes in lipid composition occur which indicates that fatty acids deposited in the egg by the female worm are used for phospholipid biosynthesis required for membrane formation in the developing miracidium.

Schistosoma haematobium infection is associated with lower serum cholesterol levels and improved lipid profile in overweight/obese individuals

“…Although adult schistosomes cannot oxidize exogenous FA [26], they can use and modify host lipid for biosynthetic purposes by scavenging cholesterol and incorporating FA as phospholipids and neutral lipids in the worm eggs, notably for membrane formation of the developing miracidium [27]. It is therefore tempting to speculate that part of the reduction in some lipoprotein and TG species observed in S. haematobium-infected individuals might result from their active transfer to the eggs produced by female worms and their subsequent elimination in the urine.…”

ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica

“…[28][29][30] However, effects of metabolic disorders on Schistosoma and regulation of immune response in many diseases. [31][32][33][34] Therefore, study on the role of ApoE indicates an exciting potential for exploring the mechanism of hepatic immunopathology in schistosomiasis.…”

“…It has been demonstrated that host fat are essential elements for development of S mansoni adults and egg production. 33 Since schistosomes cannot produce their own fatty acids, the acquisition of fat from hosts is a key process necessary for egg production. Fecund females have extensive fat stores, mostly in the form of TG, for egg production and cease to produce eggs once their fat reserves exhausted.…”

Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy

“…PHX is thought to be an inhibitor of carnitine palmitoyl transferase enzymes, namely CPT-1 and CPT-2 and impact long-chain fatty acid metabolism [9,10]. In contrast to previous findings, recent advances in Schistosoma metabolism showed that this parasite lacks CPT-1 and CPT-2 [11][12][13] and that fatty acid oxidation still remains controversial in schistosomes [11,14], therefore the mechanism of action of PHX in this parasite is yet to be clarified.…”

“…In mammals, PHX is thought to impact the lipid metabolism by acting as inhibitors of CPT-1 and CPT-2 enzymes [8], whose role is to carry lipids inside mitochondrial for fatty acid oxidation [13]. While the genes encoding CPT-1 and -2 seem to be absent within the Schistosoma genome [11][12][13], in our previous study we demonstrated that female parasites treated with sub-lethal doses of PHX, showed accumulation of lipids within the vitellarium (lipid droplets) [3]. Importantly, the PHX treatment also decreases egg-laying in vitro in agreement with what previously reported on studies with the CPT-1 inhibitor etomoxir, that inhibited depletion of lipid reserves in fecund females worms in vitro and impaired schistosome egg production as well [14].…”