AN IDER MUTANT OF MYCOBACTERIUM-SMEGMATIS HAS DEREPRESSED SIDEROPHOREPRODUCTION AND AN ALTERED OXIDATIVE-STRESS RESPONSE

The mycobacterial IdeR protein is a homologue of the diphtheria-toxin repressor DtxR. We have previously demonstrated that Mycobacterium tub erculosis IdeR, like DtxR, represses transcription of Corynebacterium diphtheriae iron-regulated promoters in vivo and binds to C. diphtheri ae operators in a metal-dependent manner in vitro. We show here that i deR mutants of M. smegmatis, constructed by allelic replacement, were defective in their ability to repress siderophore biosynthesis in the presence of iron. They were also more sensitive to hydrogen peroxide a nd had decreased levels of catalase/peroxidase (KatG) and manganese su peroxide dismutase (Mn-SOD). This indicates that IdeR is a negative re gulator of siderophore production and is required for the response to superoxide- and hydrogen peroxide stress. We propose that IdeR is the mycobacterial counterpart of the Escherichia coil Fur protein, i.e. it is a pleiotropic regulator that couples iron metabolism to the oxidat ive-stress response.