Gram-negative bacteria utilize type III secretion systems (T3SS) to deliver effector proteins into eukaryotic cells and alter host cell functions. We demonstrate that Bsp22, the most abundantly secreted Bordetella T3SS protein, is a member of a novel T3SS tip complex family and may be used to protect against Bordetella infection in vivo. We also describe two proteins: the Bordetella type III secretion substrate specificity switch (T3S4), BscP, and BscU, a member of the FIhB/YscU family of proteins, as unique regulators required for secretion of the tip complex and translocators. Interestingly, neither of these regulators are required for effector secretion. We present the crystal structure of BscU and its non-cleavable mutant and identify key residues that play a role in transmitting the signal for secretion through the T3SS apparatus. |