Metabolomes and Lipidomes of the Infective Stages of the Gastrointestinal nematodes, Nippostrongylus brasiliensis and Trichuris muris.

Karma Yeshi,Darren J Creek,Dovile Anderson,Phurpa Wangchuk,Alex Loukas,Luke Becker,Edita Ritmejerytė

doi:10.3390/metabo10110446

Abstract

Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts’ tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and pathogenicity of human hookworms and whipworms, we investigated the metabolomes of the infective stage of Nippostrongylus brasiliensis third-stage larvae (L3) which penetrate the skin and Trichuris muris eggs which are orally ingested, using untargeted liquid chromatography-mass spectrometry (LC-MS). We identified 55 polar metabolites through Metabolomics Standard Initiative level-1 (MSI-I) identification from N. brasiliensis and T. muris infective stages, out of which seven were unique to excretory/secretory products (ESPs) of N. brasiliensis L3. Amino acids were a principal constituent (33 amino acids). Additionally, we identified 350 putative lipids, out of which 28 (all known lipids) were unique to N. brasiliensis L3 somatic extract and four to T. muris embryonated egg somatic extract. Glycerophospholipids and glycerolipids were the major lipid groups. The catalogue of metabolites identified in this study shed light on the biology, and possible therapeutic and diagnostic targets for the treatment of these critical infectious pathogens. Moreover, with the growing body of literature on the therapeutic utility of helminth ESPs for treating inflammatory diseases, a role for metabolites is likely but has received little attention thus far.

Highlights

Infection with parasitic helminths is one of the most common and detrimental of the neglected tropical diseases [1]
The replicates of the L3 somatic tissue extract were named of N. brasiliensis, we prepared two biological samples—somatic tissue extract and excretory/secretory products (ESPs)—and each
Parasites have co-evolved with humans for millennia and produce ESPs that allow them to navigate through circuitous pathways to reach the gut, where they survive for a prolonged period

Summary

Introduction

Infection with parasitic helminths is one of the most common and detrimental of the neglected tropical diseases [1]. Eight out of the 17 recognised neglected tropical diseases are caused by parasitic helminths [2]. More than 1.5 billion people (approximately 24% of the world’s population) are infected with soil-transmitted helminth infections (STHIs) [3] and contribute to a substantial burden of human disease and disability worldwide. Unlike T. trichiura and A. lumbricoides, which are prevalent among young children, N. americanus and A. duodenale tend to infect older. Soil-transmitted helminths are ubiquitous in tropical climates and rural temperate areas with inadequate sanitation facilities—that is, mostly poverty-stricken areas across the world. There is no vaccine for any human helminth infections, and current control efforts focus on mass drug administration, which is only partially effective [6].

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