BBSRC Liverpool 2 - The structure and function of nematode pathogenicity islands

Parasitic nematodes are very common and important parasites in natural ecosystems, in livestock, and in human populations, but we do not understand how they compete to exploit their hosts, nor how they are pathogenic to hosts, nor how their pathogenicity evolves. In microparasites, these phenomena are well understood and often effected by pathogenicity islands.

We have discovered genomic clusters of highly-diverse, transposon-enriched parasitism genes in the parasitic nematode Strongyloides that we think are "pathogenicity islands". We call these pathogenicity islands by analogy with bacterial pathogenicity islands because: (i) they are large genomic features and (ii) we hypothesise, that they are central to nematode infection and pathogenicity; they differ from bacterial pathogenicity islands because they are not inherited by horizontal gene transfer.

We have evidence of similar gene clusters in other parasitic nematodes that have evolved parasitism independently of Strongyloides, suggesting that such islands may be widespread genomic features of parasitic nematodes. If so, the discovery of parasitic nematode pathogenicity islands could be transformative in understanding nematode parasitism and pathogenicity, its molecular and genomic basis, and its evolution. We hypothesise that these islands underlie different infection phenotypes with which parasites compete to exploit hosts, to further their own fitness.

We now propose to investigate this hypothesis in Strongyloides. We will do this by precisely resolving the islands' detailed structure and patterns of diversity in wild Strongyloides, and discover the patterns of co-infection among different pathogenicity island genotypes in naturally infected wild rat populations. We will then predict the functional consequences of genetic diversity in pathogenicity islands and test these predictions in vivo.