Inhibition of AlgU by MucA is required for viability in Pseudomonas aeruginosa

causes chronic lung infections in people with cystic fibrosis (CF), and this bacterium undergoes selection in the CF lung environment over the course of these life-long infections. One genetic adaptation frequently observed in CF isolates is mutation of MucA inhibits the sigma factor AlgU. Clinical mutations lead to misregulation of AlgU, resulting in a mucoid bacterial phenotype that is associated with poor CF disease outcomes. Here we show that paradoxically a portion of the gene is essential for viability. We demonstrate that is no longer essential in a strain lacking , and alleles that encode for proteins that do not bind to AlgU are insufficient for bacterial viability. Furthermore, we found that is no longer essential in mutant strains containing AlgU variants with reduced sigma factor activity, suggesting that reducing AlgU activity can suppress the requirement for . Finally, we found that overexpression of from an inducible promoter prevents cell growth in the absence of MucA, and that this phenotype can be rescued by overproduction of RpoD, the housekeeping sigma factor. Together, these results suggest that in the absence of MucA, the inability to regulate AlgU activity leads to sigma factor competition, preventing the expression of essential housekeeping genes and resulting in the loss of bacterial viability.