MucA sequesters extracytoplasmic function (ECF) σ22 (algT/U encoded) from target promoters including PalgD for alginate biosynthesis. We have shown that cell wall stress (e.g. d-cycloserine) is a potent inducer of the algD operon. Here we showed that MucB, encoded by the algT-mucABCD operon, interacts with MucA in the sigma–sequestration complex. We hypothesized that AlgW protease (a DegS homologue) is activated by cell wall stress to cleave MucA and release σ22. When strain PAO1 was exposed to d-cycloserine, MucA was degraded within just 10 min, and σ22 was activated. However, in an algW mutant, MucA was stable with no increased σ22 activity. Studies on a yaeL mutant, defective in an RseP/YaeL homologue, suggest that YaeL protease cleaves MucA only after cleavage by AlgW. A defect in mucD, encoding a periplasmic HtrA/DegP homologue, caused MucA instability, suggesting MucD degrades cell wall stress signals. Overall, these data indicate that cell wall stress signals release σ22 by regulated intramembrane proteolysis (RIP). Microarray analyses identified genes of the early and late cell wall stress stimulon, which included genes for alginate production. The subset of genes in the σ22 regulon was then determined, which included gene products predicted to contribute to recovery from cell wall stress.