Dual regulation of mucoidy in Pseudomonas aeruginosa and sigma factor antagonism

The conversion to mucoid, exopolysaccharide alginate-overproducing phenotyp e in Pseudomonas aeruginosa during chronic respiratory infections in cystic fibrosis patients occurs via mutations that activate the alternative sigma factor AlgU (sigma(E)). In this study, we demonstrate that conversion to m ucoidy can be caused via a second, algU-independent pathway, in which algin ate production and transcription of the critical algD promoter depend on an other alternative sigma factor, RpoN (sigma(54)). The algD promoters depend ent on sigma(54) and sigma(E) showed a complete overlap resulting in identi cal mRNA 5' ends. The two pathways were not independent, as sigma(54) also repressed sigma(E)-dependent transcription of algD both in vitro and in viv o. The negative regulatory effect of sigma(54) on sigma(E)-dependent algD e xpression was based on sigma(54) binding to the algD promoter and its inter ference with sigma(E)-dependent transcription. This phenomenon, referred to here as sigma factor antagonism, reflects the unique properties of sigma(5 4), which lacks an intrinsic ability to form open transcription initiation complexes. We propose that this peculiar feature of sigma(54) has evolved i n part to allow its recruitment as a repressor of certain promoter subsets. The repression of algD by sigma(54) also depends on environmental conditio ns, supporting the notion that sigma factor antagonism plays a physiologica l role in controlling alginate production in P. aeruginosa during adaptatio n to different ecological sites (e.g. biofilm development, stress and other growth conditions) and unique environments in the chronically infected hos t.