CONTROL OF ALGU, A MEMBER OF THE SIGMA(E)-LIKE FAMILY OF STRESS SIGMA-FACTORS, BY THE NEGATIVE REGULATORS MUCA AND MUCB AND PSEUDOMONAS-AERUGINOSA CONVERSION TO MUCOIDY IN CYSTIC-FIBROSIS

The alternative sigma factor AlgU (Pseudomonas aeruginosa sigma(E)) is required for full resistance of P. aeruginosa to oxidative stress and extreme temperatures. AlgU also controls conversion of P. aeruginosa to the mucoid, alginate-overproducing phenotype associated with lethal infections in cystic fibrosis patients. Mutations that cause conversi on to mucoidy in cystic fibrosis isolates occur frequently in mucA, th e second gene within the algU mucABCD gene cluster. Here we analyze th e biochemical basis of conversion to mucoidy, MucA was shown to act as an anti-sigma factor by binding to AlgU and inhibiting its activity, MucB, another negative regulator of AlgU, was localized in the peripla sm. MucB exerts its function from this compartment, since deletion of the leader peptide and the cytoplasmic location of MucB abrogated its ability to inhibit mucoidy. These data support a model in which a mult icomponent system, encompassing an anti-sigma factor and elements in t he periplasmic compartment, modulates activity of AlgU. Since factors controlling AlgU are conserved in other gram-negative bacteria, the pr ocesses controlling conversion to mucoidy in P. aeruginosa may be appl icable to the regulation of AlgU (sigma(E)) equivalents in other organ isms.