Integrated activities of two alternative sigma factors coordinate iron acquisition and uptake by Pseudomonas aeruginosa.

Alternative sigma (σ) factors govern expression of bacterial genes in response to diverse environmental signals. In Pseudomonas aeruginosa σ directs expression of genes for production of a siderophore, pyoverdine, as well as a toxin and a protease. σ directs expression of a receptor for ferripyoverdine import. Expression of the genes encoding σ and σ is iron-regulated and an antisigma protein, FpvR , post-translationally controls the activities of the sigma factors in response to the amount of ferripyoverdine present. Here we show that iron represses synthesis of σ to a far greater extent than σ . In contrast ferripyoverdine exerts similar effects on the activities of both sigma factors. Using a combination of in vivo and in vitro assays we show that σ and σ have comparable affinities for, and are equally inhibited by, FpvR . Importantly, in the absence of ferripyoverdine the amount of FpvR per cell is lower than the amount of σ and σ , allowing basal expression of target genes that is required to activate the signalling pathway when ferripyoverdine is present. This complex interplay of transcriptional and post-translational regulation enables a co-ordinated response to ferripyoverdine but distinct responses to iron.