Oxidative Stress Control by Apicomplexan Parasites

Bosch, Soraya Soledad; Kronenberger, Thales; Meissner, Kamila Anna; Zimbres, Flávia M.; Stegehake, Dirk; Izui, Natália M.; Schettert, Isolmar Tadeu; Liebau, Eva; Wrenger, Carsten

doi:10.1155/2015/351289

Cited by 42 publications

(34 citation statements)

References 118 publications

(132 reference statements)

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“…To combat these toxic effects, the antioxidant system consists of a network of proteins that function directly to reduce oxidative damage and includes enzymes involved in the recycling of redox proteins, enzymes that participate in the synthesis of antioxidants, and enzymes that catalyze the conversion of reactive species into less harmful molecules 51 . This is of particular importance in intracellular parasites that must contend not only with the oxidative stresses produced during division and metabolism but also those generated by the host 80 . In the case of Plasmodium falciparum , disruption of the 2-Cys peroxiredoxin PfTPx-1 resulted in parasites that were more readily killed by paraquat and sodium nitroprusside 81 .…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

Charvat

Arrizabalaga

2016

Sci Rep

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The ionophore monensin displays potent activities against several coccidian parasites of veterinary and medical importance including the opportunistic pathogen of humans, Toxoplasma gondii. While monensin is used widely in animals, toxicity impedes its use in humans. Nonetheless, given its potency, understanding its mode of action would reveal vulnerable aspects of the parasite that can be exploited for drug development. We previously established that monensin induces Toxoplasma to undergo cell cycle arrest and an autophagy-like cell death. Interestingly, these effects are dependent on the mitochondrion-localized TgMSH-1 protein, suggesting that monensin disrupts mitochondrial function. We demonstrate that monensin treatment results in decreased mitochondrial membrane potential and altered morphology. These effects are mitigated by the antioxidant compound N-acetyl-cysteine suggesting that monensin causes an oxidative stress, which was indeed the case based on direct detection of reactive oxygen species. Moreover, over-expression of the antioxidant proteins glutaredoxin and peroxiredoxin 2 protect Toxoplasma from the deleterious effects of monensin. Thus, our studies show that the effects of monensin on Toxoplasma are due to a disruption of mitochondrial function caused by the induction of an oxidative stress and implicate parasite redox biology as a viable target for the development of drugs against Toxoplasma and related pathogenic parasites.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

Charvat

Arrizabalaga

2016

Sci Rep

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“…In mammalian hosts, B. microti lives in an oxidative stress environment during the erythrocytic stage. It is thus exposed to the toxic effects of ROS, which can damage membrane lipids, nucleic acids, and proteins ( Bosch et al, 2015 ). Thus, to address this challenge and maintain a redox balance, parasites employ a variety of antioxidant systems.…”

Section: Introductionmentioning

confidence: 99%

Babesia microti Aldo-keto Reductase-Like Protein Involved in Antioxidant and Anti-parasite Response

et al. 2017

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The intraerythrocytic apicomplexan Babesia microti is the primary causative agent of human babesiosis, which is an infectious disease that occurs in various regions around the world. Although the aldo-keto reductases (AKRs) of this parasite have been sequenced and annotated, their biological properties remain unknown. AKRs are a superfamily of enzymes with diverse functions in the reduction of aldehydes and ketones. In the present study, we cloned the full-length cDNA of a B. microti aldo-keto reductase-like protein (BmAKR) and analyzed the deduced amino acid sequence of the BmAKR protein. This protein has a conserved AKR domain with an N-terminal signal sequence. Bmakr was upregulated on the 8th day after infection, whereas it was downregulated during the later stages. The recombinant protein of BmAKR was expressed in a glutathione S-transferase-fused soluble form in Escherichia coli. Western blot analysis showed that the mouse anti-BmAKR antibody recognized native BmAKR from a parasite lysate. Immunofluorescence microscopy localized BmAKR to the cytoplasm of B. microti merozoites in mouse RBCs in this study. Bmakr expression was significantly upregulated in the presence of oxidant stress. Atovaquone, a known anti-babesiosis drug, and robenidine, a known anti-coccidiosis drug, induced upregulation of Bmakr mRNA, thereby suggesting that Bmakr may be involved in anti-parasite drug response.

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“…To counteract this oxidative stress, parasites are equipped with specific ROSdetoxifying mechanisms that are critical for parasite survival and the establishment of infection[53]. The superoxide dismutase SOD2 (NCLIV_058830) had a 2-fold higher abundance in Nc-Spain1H TZP at 12 hpi.…”

mentioning

confidence: 99%

Integrative transcriptome and proteome analyses define marked differences between Neospora caninum isolates throughout the tachyzoite lytic cycle

Horcajo

Xia

Randle

et al. 2018

Journal of Proteomics

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The molecular basis that governs biological variability in N. caninum and the pathogenesis of neosporosis has not been well-established yet. This is the first study in which high throughput technology of LC-MS/MS and RNA-Seq is used to investigate differences in the proteome and transcriptome between two well-characterized isolates. Both isolates displayed different proteomes throughout the lytic cycle and the transcriptomes also showed marked variations but were inconsistent with the proteome results. However, both datasets identified a pre-bradyzoite status of the low virulence isolate Nc-Spain1H. This study reveals interesting insights into likely mechanisms involved in virulence in N. caninum and shed light on a subset of proteins that are potentially involved in the pathogenesis of this parasite.

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Oxidative Stress Control by Apicomplexan Parasites

Cited by 42 publications

References 118 publications

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

Babesia microti Aldo-keto Reductase-Like Protein Involved in Antioxidant and Anti-parasite Response

Integrative transcriptome and proteome analyses define marked differences between Neospora caninum isolates throughout the tachyzoite lytic cycle

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