role of ferritins in the physiology of Salmonella enterica sv. Typhimurium: a unique role for ferritin B in iron-sulphur cluster repair and virulence

• Published in: Molecular microbiology 2007-03, Vol.63 (5), p.1495-1507
• Main Authors: Velayudhan, Jyoti, Castor, Margaret, Richardson, Anthony, Main-Hester, Kara L, Fang, Ferric C
• Format: Article
• Language: English
• Subjects: Aconitate Hydratase - metabolism; Animals; Anti-Bacterial Agents - pharmacology; Bacterial proteins; Bacterial Proteins - physiology; Bacteriology; Biological and medical sciences; Cells; Cytoplasm - chemistry; Female; Ferritins - genetics; Ferritins - physiology; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Regulation, Bacterial; Hydrogen Peroxide - pharmacology; Iron; Iron - metabolism; Liver - microbiology; Mice; Mice, Inbred C3H; Microbiology; Miscellaneous; Oxidative Stress; Repressor Proteins - physiology; RNA, Bacterial - analysis; RNA, Messenger - analysis; Rodents; Salmonella enterica; Salmonella Infections, Animal - microbiology; Salmonella typhimurium - pathogenicity; Salmonella typhimurium - physiology; Survival; Virulence
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2007.05600.x

Ferritins are ubiquitous iron (Fe) storage proteins that play a fundamental role in cellular Fe homeostasis. The enteric pathogen Salmonella enterica serovar Typhimurium possesses four ferritins: bacterioferritin, ferritin A, ferritin B and Dps. The haem-containing bacterioferritin (Bfr) accounts for the majority of stored Fe, followed by ferritin A (FtnA). Inactivation of bfr elevates the intracellular free Fe concentration and enhances susceptibility to H₂O₂ stress. The DNA-binding Dps protein provides protection from oxidative damage without affecting the steady-state intracellular free Fe concentration. FtnB appears to be particularly important for the repair of oxidatively damaged Fe-sulphur clusters of aconitase and, in contrast to Bfr and FtnA, is required for Salmonella virulence in mice. Moreover, ftnB and dps are repressed by the Fe-responsive regulator Fur and induced under conditions of Fe limitation, whereas bfr and ftnA are maximally expressed when Fe is abundant. The absence of a conserved ferroxidase domain and the potentiation of oxidative stress by FtnB in some strains lacking Dps suggest that FtnB serves as a facile cellular reservoir of Fe²⁺.