Plasmodium falciparum uses vitamin E to avoid oxidative stress

Abstract

Background Plasmodium falciparum is sensitive to oxidative stress in vitro and in vivo, and many drugs such as artemisinin, chloroquine and cercosporin interfere in the parasite’s redox system. To minimize the damage caused by reactive radicals, antioxidant enzymes and their substrates found in parasites and in erythrocytes must be functionally active. It was shown that P. falciparum synthesizes vitamin E and that usnic acid acts as an inhibitor of its biosynthesis. Vitamin E is a potent antioxidant that protects polyunsaturated fatty acids from lipid peroxidation, and this activity can be measured by detecting its oxidized product and by evaluating reactive oxygen species (ROS) levels.ResultsHere, we demonstrated that ROS levels increased in P. falciparum when vitamin E biosynthesis was inhibited by usnic acid treatment and decreased to basal levels if exogenous vitamin E was added. Furthermore, we used metabolic labelling to demonstrate that vitamin E biosynthesized by the parasite acts as an antioxidant since we could detect its radiolabeled oxidized product. The treatment with chloroquine or cercosporin of the parasites increased the ratio between α-tocopherolquinone and α-tocopherol.ConclusionsOur findings demonstrate that vitamin E produced endogenously by P. falciparum is active as an antioxidant, probably protecting the parasite from the radicals generated by drugs.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2402-3) contains supplementary material, which is available to authorized users.

Neotropical migratory and resident birds occurring in sympatry during winter have distinct haemosporidian parasite assemblages

“…Sussmann et al, 2017). In an experimental study of mice, oxidative stress reduced by 90% the survival of liver stages of the rodent malaria parasite Plasmodium berghei, reducing infection intensity in later stages of the parasite life cycle within the rodent host (Zuzarte-Luís et al, 2017).…”

Tocopherol biosynthesis in Leishmania (L.) amazonensis promastigotes

“…The present study showed for the first time that the parasite L. amazonensis promastigotes biosynthesizes vitamin E. Although vitamin E biosynthesis is characteristic of photosynthetic eukaryotes , it was also demonstrated in P. falciparum . In L. amazonensis , using two different RP‐HPLC systems and the metabolic precursor [1‐ (n) ‐3H]‐phytol, two fractions with the same retention time as the α‐ and γ‐tocopherol standards were detected in the promastigotes.…”

“…Our results also indicate that this biosynthesis can be strongly inhibited by the HPPD irreversible enzyme‐binding inhibitor usnic acid and moderately by HPPD inhibitor nitisinone , possibly due to its reversible enzyme‐binding in most studied organisms . The 4‐hydroxyphenylpyruvate dioxygenase catalyses the conversion of p ‐hydroxyphenylpyruvic acid to homogentisic acid , a direct precursor of vitamin E and plastoquinone in most photosynthetic organisms except in cyanobacteria, where plastoquinone is thought to be biosynthesized by an alternative pathway .…”

Terpenes as Potential Antimalarial Drugs

“…It was demonstrated that the vitamin K2 biosynthesized by the parasite acts as electron transporter in the respiratory chain in microaerophilic conditions and that this biosynthesis can be inhibited treating parasite culture with RO 48-8071, a specific inhibitor of manequinone-4 biosynthesis [24]. The biosynthesis of tocopherol (vitamin E) was characterized in the parasite and has been shown essential for antioxidant that protects against environmental stress, including maintaining ROS levels [46]. The parasite lives in a pro-oxidant environment that contains oxygen and iron and therefore have evolved extensive detoxifying and protective mechanisms, which both limit the production of and potential damage by ROS [27,46].…”