MucA

mucA is a gene in Pseudomonas aeruginosa that encodes the anti-sigma factor MucA, a membrane-anchored protein that binds the extracytoplasmic function sigma factor AlgU and inhibits its activity. By sequestering AlgU at the cytoplasmic membrane, MucA prevents AlgU-dependent transcription of genes involved in alginate biosynthesis and other stress-responsive genes under non-stress conditions.

Under envelope stress or during sigma factor regulation, proteolytic cleavage of MucA enables AlgU to associate with RNA polymerase, initiating transcription of the alginate biosynthesis operon (including algD) and other AlgU-regulated genes. The periplasmic portion of MucA interacts with MucB; proteolysis is initiated by periplasmic proteases such as DegS/AlgW in response to misfolded outer membrane proteins, followed by further cytoplasmic proteolysis to liberate AlgU.

In clinical P. aeruginosa isolates from cystic fibrosis patients, loss-of-function mutations in mucA, especially mucA22, lead to constitutive AlgU activity and a mucoid phenotype characterized by overproduction of alginate. This mucoidy enhances biofilm formation, persistence in the host, and antibiotic tolerance, contributing to chronic infections. As a regulatory element of the AlgU/AlgD pathway, mucA has been studied as a model of sigma factor control and adaptive response in bacteria.