S. flexneri is one of the predominant causative agents of bacillary dysentery in the developing world. A number of animal models have been used in the past to study the pathogenesis process of S. flexneri. However, these animal models have a number of drawbacks; the most important being that most of these animal models utilize mucosal surfaces rather than the colon as the site of infection, questioning their clinical relevance and the ethical and cost implications.
My PhD project involves the use of the soil-dwelling roundworm C. elegans as a potential animal model to study the pathogenesis of S. flexneri. C. elegans was chosen as its intestinal cells share morphological similarities with human intestinal cells and its immune system shares many characteristics with the human innate immune system (suggesting that C. elegans may utilize similar response mechanisms to counter a bacterial infection as its human counterpart). Previous research done using C. elegans has shown that S. flexneri has a fatal impact on C. elegans. In order to identify the changes in molecular/biological functions that cause a Shigella infection detrimental to C. elegans, we carried out RNA-sequencing on the wild-type C. elegans strain that was exposed to S. flexneri for 6 hours. We were able to identify 6311 genes to be differentially expressed in C. elegans even within such a short time of exposure to the pathogenic bacterium. We were able to identify a number of genes involved in antioxidant defence, antimicrobial defence, iron homeostasis and autophagy within the differentially expressed genes. Using a number of knock-out and transgenic C. elegans strains and assays, I have been able to show the importance of these biological processes during the infection and develop a model that explains the pathogenesis of S. flexneri in C. elegans.