How Relevant is Caenorhabditis elegans as a Model for the Analysis of Parasitic Nematode Biology?

Abstract

Due to the development of resistance to anthelmintics there is a continuous requirement to search for new anthelmintics that act at novel sites. Until now, new anthelmintics have been discovered through screens using parasitic nematodes. However, their mode of action has often been determined through experimental approaches utilizing the free-living nematode, Caenorhabditis elegans. In this chapter, the value of C. elegans as a surrogate parasite will be considered. The phylogenetic relationship between C. elegans and parasitic nematodes suggests that C. elegans may be a preferred model for some parasitic nematodes more than others, being particularly useful for those in the same clade. In this context an important achievement has been the sequencing of the C. elegans genome followed by the genomes of a number of parasitic nematodes. This has enabled the identification of homologous and orthologous genes between C. elegans and parasitic nematodes with two particular experimental advances: (i) the identification of genes in C. elegans that are orthologous to those genes key for normal function in parasitic nematodes and (ii) the expression of parasitic nematode genes in C. elegans to facilitate their functional characterization. Examples of both will be given here. The value of the experimental tractability of C. elegans is weighed against the extent to which it provides a reliable indicator for gene function in parasitic nematodes. Also, we review the value of C. elegans in elucidating the mode of action of anthelmintics with particular reference to anthelmintics acting on nicotinic acetylcholine receptors, glutamate-gated chloride channels, and calcium-activated potassium channels. The examples highlight the use of C. elegans as a model system to identify anthelmintic drug targets. Finally, the potential impact of newer technologies encompassing microfluidics, optogenetics, and imaging on the utility of C. elegans for high-throughput anthelmintic drug discovery is addressed