Thurston lab Bacterial Pathogenesis & Immune Signaling Laboratory

We want to understand what determines the fate of intracellular bacteria. These are bacteria that are able to infect and then replicate inside host cells. To understand how bacteria survive inside cells we need to analyse both the host and the pathogen. On the host side, we study immune mechanisms localised in the cell that protect against intracellular bacteria. To complement this, we also investigate how intracellular bacteria such as Salmonella manipulate immune signalling within the cell. With the rise of antibiotic resistance, understanding these mechanisms is essential.

Often a key determinant of the virulence of this type of bacteria is the delivery of effectors, molecules that assist with bacterial colonisation into the host cell. Once delivered, these molecules promote the development of disease through diverse functions. Despite their evident importance to the outcome of infection, the functions of many effectors remain unknown.

We use a multidisciplinary approach encompassing the areas of proteomics, genetic screens, cell biology, biochemistry and structural biology to understand the function of bacterial effectors in molecular detail. Recently, work on a specific effector found in Salmonella, known as SteE, revealed that SteE makes changes to a specific enzyme that changes the way it works, a phenomenon we refer to as kinase reprogramming. Our work on SteE also revealed how certain processes can drive infected macrophages, a type of white blood cell, towards an anti-inflammatory state that is beneficial for bacterial persistence.