The iron-sulfur cluster biosynthesis regulator IscR contributes to iron homeostasis and resistance to oxidants in Pseudomonas aeruginosa

Abstract

© 2016 John Wiley & Sons, Inc. All rights reserved. IscR is an iron-sulfur (Fe-S) cluster-containing transcription regulator that is important for modulating intracellular Fe-S cluster content and controls diverse biological pathways both during normal growth and in response to stress. Among bacteria, the types of Fe-S biosynthesis systems employed as well as their regulation can vary. Here, we compare the physiological role and regulation of the isc operon of Pseudomonas aeruginosa with those of other bacteria, with particular emphasis on the regulatory protein, IscR. Expression of iscR is highly induced by exposure to various oxidants. Multiple IscR-binding sites, some of which overlap the RNA polymerase recognition site, are present in the isc operon promoters of Escherichia coli and P. aeruginosa. IscR bound at these sites precludes the binding of RNA polymerase, resulting in repression of gene expression. Physiological analysis of a P. aeruginosa iscR-inactivation mutant revealed varying cellular roles of this regulator. IscR contributes to resistance to oxidative stress. The effect of IscR on oxidative stress results from the direct regulation of oxidative stress defense genes, as well as an indirect effect on the levels of the heme-containing enzyme, catalase. IscR also functions in maintaining intracellular iron homeostasis, possibly via control of iron uptake, and is important for bacterial pathogenicity.