Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

Toxocariasis is a zoonotic disease affecting humans that is predominantly caused by Toxocara canis and T. cati, primarily parasites of dogs and cats, respectively. Toxocara generally establishes long-term infections by co-opting its host's physiological processes, while at the same time exploiting the nutritional environment. Adult stage T. canis reside in the gut of the definitive canine host where they employ a suite of strategies to combat intestinal immune responses by actively producing and releasing excretory-secretory products (ESPs). The protein component of T. canis ESPs has been widely studied, but characterisation of the non-protein ESP complement remains neglected. To characterize the secreted metabolome of Toxocara ESPs and to shed light on the parasite's metabolic processes, we profiled the ESPs of T. canis using both gas chromatography (GC) and liquid chromatography (LC) mass spectrometry approaches. We successfully identified 61 small molecules, including 41 polar metabolites, 14 medium-long chain fatty acids (MLCFAs) and six short chain fatty acids (SCFAs). We identified talose, stearic acid and isovalerate as the major compounds belonging to the polar, MLCFA and SCFA chemical classes, respectively. Most of the 61 identified metabolites appear to have been produced by T. canis via three distinct metabolic pathways - fatty acid, amino acid and carbohydrate metabolism. The majority of the identified ESPs have known biological properties, especially as immunomodulators. However, there is limited/no information on the biological roles or applications of 31 ESP biomolecules, suggesting that these may have novel activities that merit further investigation.

Keywords: Toxocara canis; excretory-secretory products; gastrointestinal nematode; helminths; metabolomics; small molecules; toxocariasis.