Metabolomic profling of the excretory–secretory products of hookworm and whipworm

Wangchuk, Phurpa, Kouremenos, Konstantinos, Eichenberger, Ramon M., Pearson, Mark, Susianto, Atik, Wishart, David S., McConville, Malcolm J., and Loukas, Alex (2019) Metabolomic profling of the excretory–secretory products of hookworm and whipworm. Metabolomics, 15. 101.

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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 specifc pharmacological functions.

Methods: N. brasiliensis and T. muris ESP were collected from adult worms and fltered using a 10 kDa cut-of 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 identifed, 36 known polar metabolites from N. brasiliensis and 35 from T. muris. A literature review of the identifed 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.

Item ID: 58809
Item Type: Article (Research - C1)
ISSN: 1573-3890
Keywords: Excretory–secretory products; Nippostrongylus brasiliensis; Trichuris muris; Gas chromatography–mass spectrometry; Small molecule metabolites; Metabolomics
Copyright Information: © Springer Science+Business Media, LLC, part of Springer Nature 2019
Funders: National Health and Medical Research Council (NHMRC), Australian Institute of Tropical Health and Medicine (AITHM)
Projects and Grants: NHMRC Peter Doherty Early Career Researcher fellowship APP1091011, AITHM Capacity Development Grant, NHMRC program grant APP1132975, NHMRC Senior Principal Research Fellowship APP1117504
Date Deposited: 02 Jul 2019 00:32
FoR Codes: 34 CHEMICAL SCIENCES > 3404 Medicinal and biomolecular chemistry > 340401 Biologically active molecules @ 30%
34 CHEMICAL SCIENCES > 3405 Organic chemistry > 340502 Natural products and bioactive compounds @ 10%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320599 Medical biochemistry and metabolomics not elsewhere classified @ 60%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 60%
97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 40%
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