Effects of Injected Iron and Siderophores on Infections in Normal and Immune Mice

Abstract

The fate of virulent and avirulent strains of Salmonella typhimurium in untreated and iron-injected mice and in transferrin-containing media demonstrated a direct relationship between bacterial virulence and the ability of bacteria to acquire transferrin-bound iron. Effects of injected iron on the development of infections with virulent and avirulent bacterial strains were determined in normal and immune mice by determinations of bacterial numbers in tissue homogenates and the mortality of infected animals. Results showed that infected and ironinjected mice died much more rapidly and frequently from overwhelming infections than infected and saline-injected mice. The infection-promoting effect of iron varied with the degree of bacterial virulence; the more virulent the bacteria, the more helpful was iron for the development of lethal infections. Siderophores promoted lethal infections in mice infected with virulent but not with avirulent bacteria. Experiments with vaccinated animals showed that iron exerted a deleterious effect on acquired immunity. Immune mice infected with virulent bacteria and injected with iron developed lethal infections as rapidly and nearly as frequently as similarly treated normal mice. Siderophores did not promote the development of lethal infections in immune mice. The effectiveness of iron, but not of siderophores, to promote bacterial infections in vaccinated mice revealed that acquired immunity is dependent upon the activity of an iron-neutralizable antibacterial system.

Iron uptake mechanisms of pathogenic bacteria

“…Enterochelin is relatively unstable [153] and poorly soluble [130]. Moreover, while enterochelin deferrates transferrin more rapidly than aerobactin at neutral pH in HEPES buffer, the relative rates are reversed in the presence of serum albumin [154].…”

“…Since the levels of free iron in vivo are well below microbial requirements, it might be expected that possession of high-affinity ironscavenging systems would constitute an important element in bacterial virulence. Certainly the presence of exogenous siderophores in animal hosts infected with pathogenic strains of Salmonella [153,239], Vibrio uulnificus [240], Yersinia [241,242] or Pseudomonas aeruginosa [243] markedly enhances the apparent virulence of these pathogens. The aerobactin system of plasmid ColV-K30 enhanced the virulence of laboratory strains of E. coli in mice, an effect which was abolished if the mice were also burdened with excess iron [144].…”

Acute iron overload in mice: pathogenesis of Salmonella typhimurium infection

“…Most in vivo experiments were performed with iron-overloaded animals. Whereas some authors only monitored increased mortality in these animals after an experimental infection (10,11,15,17,19), others were able to show an enhancing effect of iron on the bacterial counts in the infected animals without measuring the actual serum iron level in relation to the bacterial growth in the same animals (2, 4, 7-9, 16, 24). In addition to the serum iron level, the transferrin level should be measured, since the saturation of this iron-bind-ing protein with iron is thought to be an important factor for the availability of iron to the bacteria (17).…”

Role of Iron in Pathogenesis of Guinea Pigs Infected with Yersinia Enterocolitica 0:3

“…The iron availability might also include expression of other virulent factors, such as toxins (BETLEY et al, 1986), hemolysins (CAVALIERI et al, 1984), or colicin V (CHEHADE and BRAUN, 1988). In cases of experimental infection with Listeria, Pasteurella, Klebsiella, Escherichia, Yersinia, Neisseria, Shigella or Salmonella, it has been found that iron injection along with bacterial inoculum increases the bacterial virulence (BARRY and REEVE, 1977;KOCHAN et al, 1978;MILES et al, 1979).…”