Iron and infection: the heart of the matter

Abstract

Bacterial resistance to antibiotics is a major threat to clinical medicine. However, natural resistance to bacterial infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind. The availability of iron is the heart of the matter and the successful functioning of these antibacterial systems depends entirely upon an extremely low level of free ionic iron (10(-18) M) in normal tissue fluids. This in turn depends on well-oxygenated tissues where the oxidation-reduction potential (Eh) and pH control the binding of iron by unsaturated transferrin and lactoferrin. Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.

Clinical Use of Intravenous Iron: Administration, Efficacy, and Safety

“…Although IV iron has been theoretically implicated as a cause of increased infections. 70,71 Hoen et al 72 prospectively examined 985 dialysis patients receiving IV iron as part of the regimen for dialysisassociated anemia and found that, while central venous catheters, history of bacteremia, arteriovenous grafts, and immunosuppression were associated with increased risk of infections, ferritin levels and total dose of IV iron administration were not. Furthermore, in the Anker study, patients with heart failure (a relatively high-risk group)-including approximately 40% with CKD in a 6-month placebo-controlled trial-had improvements in quality of life and functional status without an increase in infections.…”

Comparison of virulence factors and expression of specific genes between uropathogenic Escherichia coli and avian pathogenic E. coli in a murine urinary tract infection model and a chicken challenge model

“…A variety of serotypes have been identified among APEC, and strains of the same O-types (O1, 2, 4, 6, 7, 8, 16, 18 and 75) are also noticeably involved in UTIs Oelschlaeger et al, 2002;Bullen et al, 2005). The common presence of a set of virulence-associated genes among APEC and UPEC strains as well as similar disease patterns and phylogenetic background indicate a genetic relationship between APEC and UPEC isolates (Kaper et al, 2004;Moulin-Schouleur et al, 2006;Ron, 2006).…”

A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction

“…This phenomenon is considered to be a defense reaction depriving bacteria of iron. 13 Though mitochondrial function during sepsis and endotoxic shock has been studied extensively, results are contradictory. Mitochondrial function during septic/endotoxic shock depends on: (i) the source of mitochondria, (ii) the experimental induction of septic/endotoxic shock, and (iii) the phase of illness.…”