Caenorhabditis elegans as an animal host to study oomycete infection: Discovery of the chitinase-like gene family, resistance genes that are transcriptionally controlled by the antagonistic paralogs pals-22 and pals-25

Abstract

The nematode Caenorhabditis elegans is used as a model system to study eukaryotic molecular responses to pathogens. These investigations have contributed to revealing key C. elegans innate immune defense mechanisms, such as the expression of inducible pathogen specific resistance genes. In general, researchers have mainly utilised pathogens not shown to naturally interact with C. elegans, or natural pathogens largely restricted to species of fungi and microsporidia. Towards the goal of expanding this field, we have identified the oomycete Myzocytiopsis humicola, as a new natural pathogen of C. elegans. Due in part to the absence of robust and genetically tractable experimental systems, animal pathogenic oomycetes encompass a diverse range of under-studied organisms. Thus, our discovery has provided us the opportunity to establish a novel and experimentally tractable pathosystem to examine animal oomycete infections. In this thesis, we will present this new experimental system, the pathogen infection strategy and how C. elegans responds transcriptionally to an oomycete infection. Additionally, we will describe the discovery of the chitinase-like (chil) genes, a novel family of uncharacterised C. elegans resistance genes, and discuss their functional role to antagonise M. humicola infection. Intriguingly, we show, chil gene expression is induced in response to pathogen detection, an ability previously not attributed to C. elegans. Finally, we will also describe our efforts to find transcriptional regulators of chil gene expression, and the discovery of the pals-22/pals-25 genes, C. elegans specific antagonistic paralogs involved in a novel mechanism that balances development against immunity. In summary, the work presented here, expands our knowledge of natural pathogens of C. elegans, introduces a new genetically tractable pathosystem to examine how animals respond to an oomycete infection, reveals a novel family of C. elegans pathogen resistance genes and a new C. elegans specific mechanism that regulates development and immunity.