Dissecting Shigella Flexneri Type Iii Secretion System Tip Complex Maturation

The type III secretion system (T3SS) is used by many Gram negative bacteria as a means for communicating with target eukaryotic cells. In the most thoroughly characterized systems, the T3SS is used to subvert normal cellular functions as a weapon in the bacterium's virulence arsenal. The T3SS machinery consists of two main structural components. The first is a basal body which is a complex assemblage of proteins that spans the bacterial periplasm and is anchored in the bacterial inner and outer membranes. The second is an exposed needle structure that is involved in sensing host cell contact and delivering the effector proteins responsible for subverting host functions directly into the eukaryotic cell's membrane and cytoplasm. The secreted effector proteins vary greatly with respect to function from one pathogen to another and these effectors ultimately determine the outcome of the pathogen-host interaction. In contrast, there is notable structural and functional homology among the type III secretion apparatuses (T3SAs) studied thus far. Despite such conservation, the mechanisms by which different T3SSs sense the environment and mature is only now being understood. The identification of protein complexes at the tip of the exposed needle that are responsible for secretion control and determination of the structures for some needle and needle tip complex proteins has provided a starting point for dissecting the conserved and divergent aspects of type Ill secretion induction. This chapter discusses the structures and mechanisms of maturation of the T3SA tip complex, focusing on the model system, Shigella flexneri.