Iron-Responsive Regulation of theHelicobacter pyloriIron-Cofactored Superoxide Dismutase SodB Is Mediated by Fur

ABSTRACTMaintaining iron homeostasis is a necessity for all living organisms, as free iron augments the generation of reactive oxygen species like superoxide anions, at the risk of subsequent lethal cellular damage. The iron-responsive regulator Fur controls iron metabolism in many bacteria, including the important human pathogenHelicobacter pylori, and thus is directly or indirectly involved in regulation of oxidative stress defense. Here we demonstrate that Fur is a direct regulator of theH. pyloriiron-cofactored superoxide dismutase SodB, which is essential for the defense against toxic superoxide radicals. Transcription of thesodBgene was iron induced inH. pyloriwild-type strain 26695, resulting in expression of the SodB protein in iron-replete conditions but an absence of expression in iron-restricted conditions. Mutation of thefurgene resulted in constitutive, iron-independent expression of SodB. RecombinantH. pyloriFur protein bound with low affinity to thesodBpromoter region, but addition of the iron substitute Mn2+abolished binding. The operator sequence of the iron-free form of Fur, as identified by DNase I footprinting, was located directly upstream of thesodBgene at positions −5 to −47 from the transcription start site. The direct role of Fur in regulation of theH. pylori sodBgene contrasts with the small-RNA-mediatedsodBregulation observed inEscherichia coli. In conclusion,H. pyloriFur is a versatile regulator involved in many pathways essential for gastric colonization, including superoxide stress defense.