(A) Map of the algT/U operon. Arrows indicate promoters. (B) Model for the “activation” of σ22 activity by regulated intramembrane proteolytic (RIP) degradation of the anti-sigma factor MucA. Under nonstress conditions, σ22 activity is low due to its sequestration at the inner membrane by the MucA-MucB complex. In response to cell wall stress (e.g., d-cycloserine), AlgW cleaves MucA in the C terminus and then RseP (YaeL) and ClpXP cleave the MucA N-terminal region, releasing σ22 from posttranslational repression. This allows σ22 to complex with core RNA polymerase, thus increasing transcription of target promoters in the σ22 stimulon, which includes PalgD of the alginate biosynthetic operon. Abbreviations: OM, outer membrane; PG, peptidoglycan; IM, inner membrane.