Effects of iron chelators and iron overload on Salmonella infection

Abstract

INCREASED susceptibility to infectious disease is observed in iron-overloaded states such as β-thalassaemia major and in haemolytic states such as sickle cell disease or Bartonellosis^1,2. The virulence of Escherichia coli, Listeria monocytogenes, Salmonella typhimurium and other pathogens can be increased by administration of iron compounds to the host, and transferrin-induced inhibition of bacterial growth can be reversed by saturating transferrin^3–6. Plasma and secretory iron-binding proteins such as transferrin and lactoferrin may function in host defence by limiting the availability of iron to invading pathogens⁷. Many microorganisms synthesise iron-binding compounds when little iron is available⁸; these compounds may compete with host iron-binding mechanisms. We report here the effects of iron-chelating drugs on this competition for iron in S. typhimurium infection in normal and iron-overloaded mice. Desferrioxamine (DF), a hydroxamic acid, and2,3-dihydroxy-benzoic acid (2,3-DHB), a phenolic iron chelator, represent two classes of iron-chelating compounds which are being tested in chelation therapy for iron overload. Our data provide evidence that DF increases iron availability to wild type S. typhimurium, promoting bacterial growth and thus enhancing virulence.