FIGURE 8.

Unchecked AlgU activity in the absence of MucA leads to bacterial cell death. Under conditions of no envelope stress (left), the full-length MucA (red) binds strongly to AlgU (green star), leaving very little free AlgU to interact with the RNAP (grey oval). Therefore, the AlgU regulon (green arrow) is in the “off” state (red X). Under conditions of envelope stress or in strains containing mucA mutations that lead to a truncated product (middle), a cleaved cytosolic form of MucA is produced. This form can still interact with and inhibit AlgU. However, the strength of the interaction is weaker than with the full-length MucA, allowing for a pool of free AlgU that can then bind to and recruit RNAP to the promoters of its regulon. Under such conditions, the AlgU regulon, which includes algU and mucA, is activated and in the “on” state (green up arrows). However, because of the feedback on MucA, negative regulation of AlgU activity is still present. In the absence of mucA (right), there is no MucA to inhibit AlgU. All of the AlgU is free to interact with the core RNAP. This leads to high expression of the AlgU regulon and overproduction of AlgU itself. Under such strong positive feedback and in the absence of the negative regulator, the unchecked AlgU activity leads to cell death