Control of type III-mediated virulence by a key bacterial signal (MALONE_J17DTP1)

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The bacterial Type III Injectisome T3I is a needle-like structure that delivers effectors and toxins directly into host cells. The T3I plays a crucial role in pathogenicity and host infection in many bacteria, including the major human and plant pathogens P. aeruginosa and P. syringae. We recently showed that a crucial component of the T3I; the export ATPase complex, binds specifically to the signalling molecule cyclic-di-GMP (cdG), a key regulator of bacterial behaviour associated with virulence control in many bacterial pathogens.Defining the relationship between the T3I and cdG is key to understanding T3I regulation during bacterial infections.In this project, we will use a combination of genetics, biochemistry and structural biology to define how cdG-binding controls the T3Is of P. aeruginosa and P. syringae. The student will construct specific cdG-binding mutants in both species, and characterise them for virulence and effector protein export. These experiments will be supported by in-depth biochemical analysis of purified ATPase proteins. The emerging model for cdG-ATPase control will be refined by structural characterisation by cryo-EM and X-ray crystallography.