Apicomplexan Parasites Are Subject to Oxidative Stress from Their Host Cells

Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis. Apicomplexan parasites are the causative agents of several different diseases: malaria (Plasmodium spp.), toxoplasmosis (Toxoplasma spp.), cryptosporidiosis (Cryptosporidium spp.), and babesiosis (Babesia spp.). Apicomplexa form a large group of complex unicellular eukaryotes and belong to the higher group of the Alveolata along with Chromerida, dinoflagellates, and ciliates. Within the Apicomplexa phylum, all parasites have an infective stage, the sporozoite. The sporozoites enter the host via typical invasion machinery consisting of the apical complex, which is composed of distinct organelles such as rhoptries, micronemes, and dense granules [1]. This process is actin-myosin dependent and subsequently a new host-derived membrane, the parasitophorous vacuole, surrounds the parasite. The life cycles of these parasites are complex, containing asexual and sexual reproduction. However, all these parasites invade cells and have to adapt to the intracellular environment of their hosts. In particular, the apicomplexan parasites have to deal with the oxidative level inside their host cells. Reactive oxygen species (ROS) and oxidative stress are the result of an aerobic metabolism that generates highly reactive metabolites of molecular oxygen (O 2) in the cytosol or in organelles such as the mitochondria or the peroxisomes [2]. These oxygen metabolites comprise superoxide anions (O 2 • −) and hydrogen peroxides (H 2 O 2) or the highly reactive hydroxyl radical (OH •) that is formed in the presence of metal ions via the Fenton and/or Haber-Weiss reactions [3]. Severe discrepancies in the ROS level can induce oxidative modifications in the indispensable cellular macromolecules such as DNA, proteins, and lipids [4], ultimately leading to cell death. In order to tackle this challenge, parasites have developed a variety of different antioxidant systems such as the thioredoxin-and glutaredoxin-systems. These systems act as thiol/disulfide pairs and are thereby involved in controlling the redox state of the cell. Glutathione/glutathione disulfide (GSH/GSSG) is one of the major redox pairs that control the antioxidative capacity of the cell, while thioredoxins (Trx red /Trx ox) form an additional redox system that interacts with a different subset of proteins [5]. Trx plays an important role in different biological processes including the reduction of ribonucleotides, transcription control, and hydrogen per-oxide detoxification [6, 7]. In addition to …