Phurpa Wangchuk1, Konstantinos Kouremenos2, Ramon M Eichenberger3,4, Mark Pearson3, Atik Susianto3, David S Wishart5, Malcolm J McConville6, Alex Loukas7. 1. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Building E4, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia. phurpa.wangchuk@jcu.edu.au. 2. Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, VIC, 3010, Australia. 3. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Building E4, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia. 4. Institute of Parasitology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 266a, 8057, Zurich, Switzerland. 5. Department of Biological Science, University of Alberta, Edmonton, AB, Canada. 6. Department of Biochemistry and Molecular Biology, University of Melbourne, 30 Flemington Road, Parkville, VIC, 3010, Australia. 7. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Building E4, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia. alex.loukas@jcu.edu.au.
Abstract
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 other hand, complete elimination of parasitic helminths and other infectious pathogens has been implicated with rising rates of autoimmune and allergic disorders in developed countries. Given the enormous health impact of these parasites, it is surprising how little is known about the non-protein small metabolites of the excretory-secretory products (ESP), including their composition and pharmacological properties. OBJECTIVES: We sought proof-of-concept that Nippostrongylus brasiliensis and Trichuris muris, rodent models of two of the most important human soil-transmitted helminths, secrete small metabolites and that some of these metabolites may have specific pharmacological functions. METHODS: N. brasiliensis and T. muris ESP were collected from adult worms and filtered using a 10 kDa cut-off membrane to produce excretory-secretory metabolites (ESM). The ESM were analysed using targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry for polar and non-polar small metabolites. RESULTS: ESM from both N. brasiliensis and T. muris contained small molecules. A total of 54 small molecules (38 polar metabolites and 16 fatty acids) were identified, 36 known polar metabolites from N. brasiliensis and 35 from T. muris. A literature review of the identified compounds revealed that 17 of them have various demonstrated pharmacological activities. CONCLUSION: N. brasiliensis and T. muris secrete polar and non-polar small molecules with as many as 17 metabolites known to exhibit various pharmacological activities.
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 other hand, complete elimination of parasitic helminths and other infectious pathogens has been implicated with rising rates of autoimmune and allergic disorders in developed countries. Given the enormous health impact of these parasites, it is surprising how little is known about the non-protein small metabolites of the excretory-secretory products (ESP), including their composition and pharmacological properties. OBJECTIVES: We sought proof-of-concept that Nippostrongylus brasiliensis and Trichuris muris, rodent models of two of the most important human soil-transmitted helminths, secrete small metabolites and that some of these metabolites may have specific pharmacological functions. METHODS:N. brasiliensis and T. muris ESP were collected from adult worms and filtered using a 10 kDa cut-off membrane to produce excretory-secretory metabolites (ESM). The ESM were analysed using targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry for polar and non-polar small metabolites. RESULTS: ESM from both N. brasiliensis and T. muris contained small molecules. A total of 54 small molecules (38 polar metabolites and 16 fatty acids) were identified, 36 known polar metabolites from N. brasiliensis and 35 from T. muris. A literature review of the identified compounds revealed that 17 of them have various demonstrated pharmacological activities. CONCLUSION:N. brasiliensis and T. muris secrete polar and non-polar small molecules with as many as 17 metabolites known to exhibit various pharmacological activities.
Entities:
Keywords:
Excretory–secretory products; Gas chromatography–mass spectrometry; Metabolomics; Nippostrongylus brasiliensis; Small molecule metabolites; Trichuris muris
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