Parasitoid venom induces metabolic cascades in fly hosts
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Parasitoid wasps inject insect hosts with a cocktail of venoms to manipulate the physiology, development, and immunity of the hosts and to promote development of the parasitoid offspring. The jewel wasp Nasonia vitripennis is a model parasitoid with at least 79 venom proteins. We conducted a high-throughput analysis of Nasonia venom effects on temporal changes of 249 metabolites in pupae of the flesh fly host (Sarcophaga bullata), over a 5-day time course. Our results show that venom does not simply arrest the metabolism of the fly host. Rather, it targets specific metabolic processes while keeping hosts alive for at least 5 days post venom injection by the wasp. We found that venom: (a) activates the sorbitol biosynthetic pathway while maintaining stable glucose levels, (b) causes a shift in intermediary metabolism by switching to anaerobic metabolism and blocking the tricarboxylic acid cycle, (c) arrests chitin biosynthesis that likely reflects developmental arrest of adult fly structures, (d) elevates the majority of free amino acids, and (e) may be increasing phospholipid degradation. Despite sharing some metabolic effects with cold treatment, diapause, and hypoxia, the venom response is distinct from these conditions. Because Nasonia venom dramatically increases sorbitol levels without changing glucose levels, it could be a useful model for studying the regulation of the sorbitol pathway, which is relevant to diabetes research. Our findings generally support the view that parasitoid venoms are a rich source of bioactive molecules with potential biomedical applications.
KeywordsVenom Nasonia Sorbitol Anaerobic respiration Chitin Amino acids
We thank the National Institutes of Health (RO1GM098667) for financial support and Matthias Williams, Amanda Dolan, and Rachel Edwards, for technical assistance and Dr. Jacintha Ellers for discussions. We also thank Dr. Ryan Michalek (Metabolon, Inc.) for metabolomic analysis and helpful discussions.
Conflict of interest
Authors Mrinalini, Aisha Siebert, Jeremy Wright, Ellen Martinson, David Wheeler, and John H. Werren, declare that they have no conflict of interest.
All institutional and national guidelines for the care and use of laboratory animals were followed.
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