Understanding Hidden Antigens and Targeting Parasitic Nematodes

Nematodes can be free-living or parasitic in nature. Infections with parasitic nematodes that directly or indirectly affect the health and productivity of humans and livestock have been the subject of scientific studies for decades. Overall, the treatment and control of nematode parasites are limited and dependent on single or repeated administration of anthelmintics, a strategy that has led to true anthelmintic resistance in animals and the concern for resistance inmass drug administration programs for humans. Efforts to discover new agents that offer improved performance in efficacy, safety and convenience are complicated with many challenges (Geary et al., 2015). An alternative strategy to worm control has been vaccination, where the concept of targeting intestinal proteins as ‘hidden antigens’ (Munn, 1997) has been explored for several helminth parasites with mixed results (Bassetto et al., 2011; Morris et al., 2013; Pearson et al., 2010). Global ‘omic’ approaches are now paving the way to better understand the biology of many organisms and to help identify and/or infer functional attributes of various genes and proteins (Rosa et al., 2015; Taylor et al., 2013) that might identify “soft spots” in the organism(s) that in turn greatly narrows the large numbers of targets that could be exploited for therapeutic or prophylactic approaches. In this issue of Ebiomedicine, Wang et al. (2015) describe the establishment of a comprehensive functional database for nematode intestinal proteins. Using transcriptional and proteomic complements of representative nematodes, a selection of protein families that are universal or restricted to intestinal regions (IntFams) forms the basis of the study. While Haemonchus contortus, Ascaris suum and Trichuris suis are used as surrogates for similar niche specific humangastrointestinal infections of Necator americanus, Ascaris lumbricoides and Trichuris trichiura, inferences for clade-specific representative parasitic filarial nematodes (Brugia malayi and Loa loa) have also been derived. The study is centered on the identification of conserved IntFams (cIntFams) across all nematodes that have the potential for broadspectrum pan-nematoda control, while species or clade-specific divergent IntFams (ncIntfams) represent novel functions. There are a number of reasons that make this study interesting. Firstly, this knowledgebase provides a launchpad not only for directed research to understand inherent biological functions and pathways, but also as a gateway for the rapid identification of potential therapeutic targets. Secondly, if we consider the time and effort required for traditional drug screening in experimentally-infected animals or in-vitro screens, fusion of molecular techniques with evolutionary informatics presents a fertile ground for