Pseudomonas aeruginosa SoxR Does Not Conform to the Archetypal Paradigm for SoxR-Dependent Regulation of the Bacterial Oxidative Stress Adaptive Response

Abstract

SoxR is a transcriptional regulator that controls an oxidative stress response in Escherichia coli . The regulator is primarily activated by superoxide anion-dependent oxidation. Activated SoxR turns on transcription of a single gene, soxS , which encodes a transcriptional regulator that activates a regulon that includes dozens of oxidative stress response genes. SoxR homologues have been identified in many bacterial species, including the opportunistic pathogen Pseudomonas aeruginosa . However, the expected SoxR partner, SoxS, has not been found in P. aeruginosa . Thus, the primary gene target(s) of P. aeruginosa SoxR is unknown and the involvement of this regulator in the oxidative stress response of the bacterium remains unclear. We utilized transcriptome profiling to identify the P. aeruginosa SoxR regulon and constructed and characterized an unmarked P. aeruginosa Δ soxR mutant. We provide evidence indicating that P. aeruginosa SoxR activates a six-gene regulon in response to O ₂ ^·− -induced stress. The regulon includes three transcriptional units: (i) the recently identified mexGHI - ompD four-gene operon, which encodes a multidrug efflux pump system involved in quorum-sensing signal homeostasis; (ii) gene PA3718, encoding a probable efflux pump; and (iii) gene PA2274, encoding a probable monooxygenase. We also demonstrate that P. aeruginosa SoxR is not a key regulatory player in the oxidative stress response. Finally, we show that P. aeruginosa SoxR is required for virulence in a mouse model of intrapulmonary infection. These results demonstrate that the E. coli -based SoxRS paradigm does not hold in P. aeruginosa and foster new hypotheses for the possible physiological role of P. aeruginosa SoxR.