Use of the cytoskeleton to control Shigella infection

The intracellular bacterium Shigella flexneri is a model pathogen that can be used to address key issues in biology, including how bacteria can move inside host cells or be recognised by the immune system. Host cells employ septins, a poorly understood component of the cytoskeleton, to restrict the motility of Shigella and target them for destruction by autophagy, an important mechanism of the innate immune defence. We recently established the antibacterial activity of septin caging and discovered a fundamental link between mitochondria and the assembly of septin cages around Shigella. It is important to now fully decipher the underlying molecular and cellular mechanisms and to validate these events in vivo using relevant animal models. I developed zebrafish infection models to study the cell biology of Shigella infection in vivo and to discover new roles for septins in host defence against bacterial infection. This approach has enabled in vivo studies of single cells and the whole animal.

My findings will provide fundamental advances in understanding cellular immunity. This should provide vital clues towards understanding bacterial disease and for illuminating new therapeutic strategies.