Dynamic relocalization of the cytosolic type III secretion system components ensures specific protein secretion

Many gastrointestinal pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature effector secretion is prevented during infection. We found that at low external pH, such as in the stomach, the components at the proximal interface of the injectisome are temporarily released to the bacterial cytosol, preventing protein secretion. Low external pH is sensed in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions.