Iron Acquisition and Iron-Dependent Gene Expression in Corynebacterium diphtheriae

Abstract

The ability of bacterial pathogens to acquire iron during infection of mammalian hosts is often an essential component of the disease process. The human pathogen Corynebacterium diphtheriae utilizes a variety of iron sources, including both host iron compounds and inorganic iron for growth in iron depleted conditions. Recent studies have shown that the upper respiratory tract of humans, a region colonized by C. diphtheriae, is low in available iron, which suggests that mechanisms for acquiring iron from the host environment are essential for survival. To support growth in low iron medium, C. diphtheriae produces the siderophore corynebactin as well as systems involved in the use of heme and hemoglobin. These iron uptake systems utilize ATP-binding cassette- (ABC) type transporters and associated solute binding lipoproteins. Heme-iron acquisition also requires membrane anchored hemin- and hemoglobin-binding proteins, as well as the intracellular heme degrading enzyme HmuO. Expression of all of these iron and heme acquisition systems is coordinately regulated with that of diphtheria toxin (DT), a major virulence determinant of C. diphtheriae. Transcription of the genes encoding DT and the iron uptake systems is controlled by the Diphtheria Toxin Repressor, DtxR; a global iron-dependent regulatory factor. Expression of HmuO is modulated by the novel heme-responsive signal transduction systems, ChrAS and HrrAS.