Characterization of Tapeworm Metabolites and Their Reported Biological Activities

Abstract

Parasitic helminths infect billions of people, livestock, and companion animals worldwide. Recently, they have been explored as a novel therapeutic modality to treat autoimmune diseases due to their potent immunoregulatory properties. While feeding in the gut/organs/tissues, the parasitic helminths actively release excretory-secretory products (ESP) to modify their environment and promote their survival. The ESP proteins of helminths have been widely studied. However, there are only limited studies characterizing the non-protein small molecule (SM) components of helminth ESP. In this study, using GC-MS and LC-MS, we have investigated the SM ESP of tapeworm Dipylidium caninum (isolated from dogs) which accidentally infects humans via ingestion of infected cat and dog fleas that harbor the larval stage of the parasite. From this D. caninum ESP, we have identified a total of 49 SM (35 polar metabolites and 14 fatty acids) belonging to 12 different chemotaxonomic groups including amino acids, amino sugars, amino acid lactams, organic acids, sugars, sugar alcohols, sugar phosphates, glycerophosphates, phosphate esters, disaccharides, fatty acids, and fatty acid derivatives. Succinic acid was the major small molecule present in the D. caninum ESP. Based on the literature and databases searches, we found that of 49 metabolites identified, only 12 possessed known bioactivities.

Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

“…Interestingly, we detected many of the same T. canis metabolites, including SCFAs, in the ESPs of other nematodes including A. caninum [25] and the tapeworm Dipylidium caninum [1], which were isolated from the same canine hosts. For instance, A. caninum ESPs contained pyroglutamic acid and propionate (as well as other SCFAs) as the major constituents of their polar ESP metabolome [25].…”

“…For instance, A. caninum ESPs contained pyroglutamic acid and propionate (as well as other SCFAs) as the major constituents of their polar ESP metabolome [25]. D. caninum ESPs contained succinic acid as the major polar metabolite, while acetate was the only identified SCFA [1]. On the other hand, T. canis ESPs contain talose and isovalerate as the major constituents of the polar and SCFA fractions, respectively.…”

“…Sample derivatisation was performed as reported earlier for the GC-MS metabolomic analysis of ESPs derived from hookworms, whipworms and tapeworms [1,24,25]. The upper aqueous phase composed of 3:1 methanol:water (~900 µL) was aliquoted (50 µL) into a pulled point insert, dried using an evaporator at 30 • C (Christ RVC 2-33 CD, John Morris Scientific Australia) and then anhydrous methanol was added (50 µL).…”

“…Soil-transmitted helminths (STHs) infect and adversely affect billions of people and animals worldwide [1]. One of the most widespread public health and economically important zoonotic STH infections is toxocariasis.…”

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities

“…Although helminth proteins and their PTMs have been documented and discussed elsewhere in this review, much less is known about parasitic helminth metabolomes. The metabolomics revolution has begun to reveal small-molecule metabolites in parasitic helminth somatic extracts and ESPs [108][109][110][111]. Helminthology has been slow to adopt cutting edge metabolomics techniques [111], partly because of the difficulty in obtaining sufficient quantities of ESPs, but also because of the diversity in physicochemical properties of metabolites results in it being almost impossible for a single analytical method to provide the required full coverage of the metabolome of a given biological sample.…”