Oral Presentation Australian and New Zealand Metabolomics Conference 2018

Excretory/secretory metabolomes of the soil-transmitted nematodes Nippostrongylus brasiliensis and Trichuris muris contain pharmacologically active small molecules (#11)

Phurpa Wangchuk 1 , Konstantinos Kouremenos 2 , Alex Loukas 1
  1. Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia
  2. Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia

Introduction Soil-transmitted helminths infect billions of people, livestock and companion animals worldwide, and chronic infections with these nematodes represent a major health burden in many developing countries. On the contrary, complete elimination of worms has been implicated with autoimmune and allergic disorders in developed countries. Given the enormous health impact of these parasites, it is surprising how little is known about the molecular composition of the non-protein components of the excretory-secretory products (ESP).

Objectives. Given that the ESP represent the molecular host-parasite interface, and that parasitic helminths secrete molecules to selectively alter their host environment, we sought to characterize the ESP metabolomes of 2 rodent nematodes, Nippostrongylus brasiliensis and Trichuris muris, that are widely used as models of human hookworm and whipworm infections respectively, and explore the reported pharmacological activities of the identified metabolites.

Methods ESP was obtained from N. brasiliensis and T. muris by culturing freshly collected adult worms in a single component minimal culture media. The small molecule ESP (<10 kDa) were analysed using targeted gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) for polar and non-polar small metabolites. Literature reviews on individual small metabolites were conducted to assess their reported pharmacological activities.

Results The GC-MS analysis of ESP showed a total of 42 polar metabolites and 13 non-polar components. Thirty-six (36) known polar metabolites were identified from the ESP of N. brasiliensis and 35 were identified from the ESP of T. muris. Content analysis of the relevant literature revealed 17 of these compounds have various demonstrated pharmacological activities.

Conclusions We show that N. brasiliensis and T. muris secrete small molecules, some of which have been implicated with various pharmacological activities.