Distinct transcriptional logics of catechol siderophore transporters in Pseudomonas aeruginosa for efficient iron acquisition.

Abstract

With 21 outer-membrane transporters dedicated to iron acquisition, Pseudomonas aeruginosa possesses an extensive toolkit for securing this essential nutrient, but activates the expression only of those relevant to its immediate environment. Eighteen of these pathways rely on siderophores, two produced by P. aeruginosa and the others acquired from neighboring microorganisms through a siderophore-piracy strategy. Using fluorescent reporters and mathematical modeling, we quantified how catechol-type siderophores regulate transcription of their matched transporters, PfeA, FvbA, PirA, and PiuA. pfeA and fvbA showed switch-like induction by enterobactin and vibriobactin, starting at around 100 nM and plateauing at 1 µM. In contrast, N-(2,3-dihydroxybenzoyl)-L-serine, an enterobactin degradation product, selectively induced piuA transcription only in strains lacking endogenous siderophores, via a gradual response spanning 250 nM to 100 µM. pirA transcription was strongly induced by host catecholamines, with activation thresholds of 1 µM for epinephrine, 5 µM for norepinephrine, and 10 µM for L-DOPA, and plateaus between 30 and 150 µM. Iron repression uncovered distinct regulatory regimes: pfeA, fvbA, and pirA display biphasic Fur-dependent repression, with transcription decreasing beginning at 4 to 16 nM Fe and fully repressed by 32 µM, whereas piuA transcription began to decrease at 8 µM iron and was not fully repressed even at 2 mM. Together, these results reveal distinct transcriptional logics that allow P. aeruginosa to sense and decode a wide array of environmental catechols, integrate this information with iron availability, and thereby deploy an iron-uptake strategy finely tuned to competitive and host-associated niches.