Figure 6.

Model for DsbA-Dependent T6SS Effector Activation in Target Cells

When immature effectors are delivered by the T6SS into the periplasm of target cells containing DsbA (top), the recipient cell’s DsbA machinery catalyzes the introduction of disulfide bonds into incoming effectors, allowing them to adopt their final, active conformation. If the target is a non-self-competitor (top left), the active effector causes intoxication, for example, cell wall cleavage. If the target is a sibling cell (top right), the corresponding immunity protein intercepts the effector, preventing toxicity. Alternatively, when effectors that normally require disulfide bond formation are delivered into a competitor target cell lacking DsbA (bottom left), they remain in the inactive form and do not cause toxicity. In sibling cells, cognate periplasmic immunity proteins may also require disulfide bond formation, for example, to achieve stability. However, loss of immunity protein function in a sibling cell lacking dsbA does not lead to intoxication, because the incoming effector is also inactive (bottom right).