1. Using our understanding of interactions between helminth metabolism and host immunity to target worm survival.
- Author
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Reed, Ella K. and Smith, Katherine A.
- Subjects
- *
HELMINTH hosts , *SHORT-chain fatty acids , *CARBOHYDRATE metabolism , *HELMINTHIASIS , *UNSATURATED fatty acids , *MALATE dehydrogenase - Abstract
There is an increasing requirement for the discovery of new anthelmintics with resistance to existing drugs on the rise. Current strategies focus on targeting carbohydrate metabolism, with glycolytic enzymes and transporters proving to be attractive druggable targets; however, these often show a lack of efficacy during in vivo infections and have a lack of specificity. Recent studies have unearthed the ability of helminths to manipulate short-chain fatty acid (SCFA) and bioactive lipid production, as possible alternative immunomodulatory strategies for establishing chronic infection. There is an urgent need to establish if these metabolic pathways are critical for parasite survival, as these could present as an exciting new avenue for anthelmintic discovery. Helminths can adapt to environmental conditions in the host, utilising anaerobic processes like fermentation and malate dismutation to produce energy from carbohydrate. Although targeting carbohydrate metabolism is an established therapeutic strategy to combat helminth infection, questions remain over the metabolic pathways they employ as adults to survive and evade host immunity. Helminths also use amino acid, polyunsaturated fatty acid (PUFA), and cholesterol metabolism, a possible strategy favouring the production of immunomodulatory compounds that may influence survival in the host. Here, we discuss the significance of these differing metabolic pathways and whether targeting of helminth metabolic pathways may allow for the development of novel anthelmintics. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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