The variable response of bacteria to excess ferric iron in host tissues

The enhancement by exogenous ferric iron, both systemic and local, of the infectivity of 120 strains of bacteria, representing 17 genera, was measured in the skin of guinea-pigs. Systemic iron enhanced only 23% of 115 strains, and local iron 49% of 71 strains. Systemic iron, by an apparently anti-inflammatory action, depressed the size of lesions produced by 27 of the non-enhanced strains from nine of the genera tested. For most strains, the degree of enhancement was small, ranging from 2- to 8-fold, and often evident only with the more effective local iron; among these were some near-saprophytes like Mycobacterium phlei, M. smegmatis, Bacillus cereus and Clostridium bifermentans. Substantial enhancement, from 14- to 50-fold, was observed with the more pathogenic among the strains tested: namely BCG, Corynebacterium ovis, C. murium, Listeria monocytogenes, Erysipelothrix rhusiopathiae, Cl. perfringens, Cl. septicum, Cl. oedematiens, and some strains of Klebsiella spp., Proteus spp. and Aeromonas hydrophila. The enhancement of BCG by a single dose of iron given locally with the inoculum was only feebly manifest after 7 days, but substantial after 14--19 days, indicating the decisive effect of interference with an early humoral defence on the establishment of chronic infection some time later. Insofar as guinea-pigs whose antibacterial defences are lowered by substantial amounts of exogenous iron in the circulation represent human subjects at risk of infection because of clinical states characterised by excess of available iron, the results of the survey suggest that only a minority among the environmental bacteria can take advantage of the decreased resistance associated with such states; but that this minority is likely to include the more virulent strains in the environment.