Pan-phylum Comparison of Nematode Metabolic Potential

Abstract

Nematodes are among the most important causative pathogens of neglected tropical diseases. The increased availability of genomic and transcriptomic data for many understudied nematode species provides a great opportunity to investigate different aspects of their biology. Increasingly, metabolic potential of pathogens is recognized as a critical determinant governing their development, growth and pathogenicity. Comparing metabolic potential among species with distinct trophic ecologies can provide insights on overall biology or molecular adaptations. Furthermore, ascertaining gene expression at pathway level can help in understanding metabolic dynamics over development. Comparison of biochemical pathways (or subpathways, i.e. pathway modules) among related species can also retrospectively indicate potential mistakes in gene-calling and functional annotation. We show with numerous illustrative case studies that comparisons at the level of pathway modules have the potential to uncover biological insights while remaining computationally tractable. Here, we reconstruct and compare metabolic modules found in the deduced proteomes of 13 nematodes and 10 non-nematode species (including hosts of the parasitic nematode species). We observed that the metabolic potential is, in general, concomitant with phylogenetic and/or ecological similarity. Varied metabolic strategies are required among the nematodes, with only 8 out of 51 pathway modules being completely conserved. Enzyme comparison based on topology of metabolic modules uncovered diversification between parasite and host that can potentially guide therapeutic intervention. Gene expression data from 4 nematode species were used to study metabolic dynamics over their life cycles. We report unexpected differential metabolism between immature and mature microfilariae of the human filarial parasite Brugia malayi. A set of genes potentially important for parasitism is also reported, based on an analysis of gene expression in C. elegans and the human hookworm Necator americanus. We illustrate how analyzing and comparing metabolism at the level of pathway modules can improve existing knowledge of nematode metabolic potential and can provide parasitism related insights. Our reconstruction and comparison of nematode metabolic pathways at a pan-phylum and inter-phylum level enabled determination of phylogenetic restrictions and differential expression of pathways. A visualization of our results is available at http://nematode.net and the program for identification of module completeness (modDFS) is freely available at SourceForge. The methods reported will help biologists to predict biochemical potential of any organism with available deduced proteome, to direct experiments and test hypotheses.

Impacts of host phylogeny, feeding styles, and parasite attachment site on isotopic discrimination in helminths infecting coral reef fish hosts

“…- S. undosquamis ) examined had a positive Δ 15 N indicating at least partial reliance on direct utilization of metabolized N from host tissues. The dietary tract-associated nematodes were generally 15 N-enriched in comparison to their hosts indicating at least partial utilization of host-metabolized compounds from tissue or the taxa-dependent ability for nematodes to biosynthesize AAs from nitrogenous compounds 22 .…”

“…No change or depletion in δ 13 C does not agree with the expected 0.5-1‰ increase that is usually expected for trophic interactions 11 , but likely reflects reliance on lipids and fatty acids directly derived from the host or host diet to support helminth tissue growth. Plathelminthes and some nematodes have been found to be incapable of de novo fatty acid synthesis and to have to rely on fatty acids derived from the host 22,28 due to incomplete metabolic pathways for lipid biosynthesis. Direct uptake of fatty acids and other lipids from the host would be expected to coincide with a minimum carbon fractionation as no further metabolic processing is required, thereby maintaining the relatively low δ 13 C values associated with lipids as they are incorporated into the parasite.…”

“…blood and liver) 13,14 . This relationship should be examined further with methods that incorporate metabolic pathway techniques for target species beyond model organisms targeted for pathogenicity 21,22 . Pairings that have elevated Δ 13 C values likely reflect decreased utilization of host lipids and increased reliance on either host sugars or proteins processed through more complete metabolic pathways within the helminths to provide tissue carbon or potentially different δ 13 C compositions from different host tissues 18 .…”

“…However, there can also be considerable variation within these helminth groups 14,20 . Distinct differences for trophic discrimination in parasitic relationships are potentially caused by the combined effects of unique feeding ecologies, often reduced metabolic capabilities of the parasitic taxa being investigated 21,22 , and host metabolic effects due to parasitism 23 . Feeding ecology varies depending on whether the parasite feeds upon host tissue exclusively (on host or within; tissue type dependent 18 ), or is able to supplement with material from within the dietary tract as the host feeds or from the environment (e.g.…”

A Multi-Omics Database for Parasitic Nematodes and Trematodes

“…Updates on development and improvements have been provided in 2004[1], 2008[2], 2012[3] and 2015[4] communicating to the community information needed to facilitate dissemination of diverse datasets in a useful and usage-friendly manner. Bioinformatics tools employed to access and/or analyze the omics datasets have also been developed (NemaPath[5], HelmCoP[6], modDFS[7] and TL-microbiome[8]) and are discussed in the appropriate sections below. A very detailed bioinformatics training protocol we have developed as part of our ‘Bioinformatics Workshop for Helminth Genomics’ that was held at the Washington University’s Genome Institute in 2015 and an ‘Introduction to Nematodes’ lecture in six languages, are both provided in the left dropdown menu under “Education”.…”