Characterisation of bacterial effectors delivered by the type VI secretion system

Many bacterial virulence determinants are secreted proteins referred to as ’effectors’ that benefit the pathogen by allowing it to subvert, damage or kill the host. In pathogenic Gram-negative bacteria, secreted effectors are secreted by one of at least nine different protein secretion systems. Therefore, protein secretion systems are important virulence determinants for such bacteria. One of these systems, the type VI secretion system (T6SS), is a syringe-like nanomachine that injects effectors directly into target cells. In some pathogenic bacteria the T6SS plays a crucial role in the virulence of the bacterium by injecting effectors directly into host cells. However, uniquely, the T6SS can also inject effectors into other bacteria and it therefore plays a major role in interspecies bacterial competition. For this reason, the T6SS offers potential for development as a therapeutic agent that can be used to kill pathogenic bacteria during an infection.

The project seeks to investigate the T6SSs present in members of the genus Burkholderia. These bacteria include opportunistic human pathogens and plant pathogens. One aim of this project is to obtain more information regarding the nature of the effector proteins secreted by these systems and their mechanism of action. The other aim is to elucidate the mechanism by which an effector protein is ‘mounted’ on the T6SS so that it is injected into a target cell.