Abstract
Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute to redox biology among parasite sexes.
Highlights
The trematode Schistosoma mansoni is a long-living intravascular parasite and a major causative agent of human schistosomiasis, a chronic disease afflicting more than 240 million people worldwide [1]
Given that glutamine contributes to tricarboxylic acid cycle through α-ketoglutarate dehydrogenase complex activity, which represents an important site of mitochondrial hydrogen peroxide (H2O2) generation [99,100,101], it is possible that higher non-respiratory O2 consumption rate (OCR) induced by glutamine in male worms might result from increased Reactive oxygen species (ROS) production through αKGDHC
The percent contribution of respiratory rates to total parasite molecular oxygen (O2) utilization were from 57% to 76%, while for non-respiration varied between 23% and 42%
Summary
The trematode Schistosoma mansoni is a long-living intravascular parasite and a major causative agent of human schistosomiasis, a chronic disease afflicting more than 240 million people worldwide [1] This illness is manifested in two distinct phases: an early acute one, when infected individuals exhibit mild symptoms such as fever, diarrhea and cough [2], and a late chronic phase, when severe clinical features including liver fibrosis, portal hypertension and hepatosplenomegaly, manifest [3]. Compelling evidence indicate that increased ability to detoxify ROS in S. mansoni represent an adaptive mechanism to avoid redox imbalance and parasite cell death triggered by host immune system
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