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.
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Acknowledgements
This work was made possible due to the financial support provided by an NHMRC Peter Doherty Early Career Researcher fellowship (APP1091011) and an AITHM Capacity Development Grant to PW; an NHMRC program grant to AL (APP1132975), and senior principal research fellowship (APP1117504) to AL. The authors would like to thank Dr. Paul Giacomin for providing T. muris eggs for mouse infections.
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PW was responsible for the execution of the experimental work, data analysis and wrote the manuscript. KK executed the GC–MS and LC–MS analyses, data analyses and wrote part of the manuscript. RME raised the rats and provided Nippostrongylus brasiliensis for the study. MP and AS helped with raising the B10.BR mice for the Trichuris muris infection experiment. MJM and DSW provided technical advice on the metabolomics study design and data analysis. AL supervised the study and contributed to data analysis and writing of the manuscript. All authors critically commented on and approved the final submitted version of the paper.
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Wangchuk, P., Kouremenos, K., Eichenberger, R.M. et al. Metabolomic profiling of the excretory–secretory products of hookworm and whipworm. Metabolomics 15, 101 (2019). https://doi.org/10.1007/s11306-019-1561-y
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DOI: https://doi.org/10.1007/s11306-019-1561-y