Transcription of the Listeria monocytogenes fri gene is growth-phase dependent and is repressed directly by Fur, the ferric uptake regulator

The Listeria monocytogenes fri gene encodes the only ferritin-like protein of this pathogen, a Dps protein (DNA binding protein from starved cells). Listeria Dps, is endowed with the capacity to detoxify concurrently free iron and H2O2, is essential for virulence and is required for efficient bacterial growth at early stages of the infection process. The transcription of fri is known to depend on sigma(A) and sigma(B) factors, to be affected by growth conditions and to be derepressed in a perR (peroxide-inducible stress response regulator) mutant background. The present work shows that fri transcription is restricted to the exponential phase of growth, whereas the Dps protein has a long half-life and is detected in significant amounts also in stationary phase cells. Expression of fri is downregulated under iron-rich conditions and is controlled directly by Fur, the ferric uptake regulator, which binds within the DNA region encompassing nucleotides from position -23 to position +90 relative to the proximal sigma(A) transcription startpoint. The putative Fur-box is proposed to coincide with the putative Per-box both in sequence and position. The primary structure of L. monocytogenes Fur has a high degree of similarity with homologues of known X-ray crystal structure. The molecular model of L. monocytogenes Fur built on this basis shows that the ligands of the structural Zn(II) and of the regulatory Fe(II) are conserved and are located in positions fully compatible with their respective roles. (C) 2008 Elsevier B.V. All rights reserved.