S. aureus, Erythrocyte Hemolysins, and Heme Iron—A Nice Little Package

Abstract & Commentary

Synopsis: S. aureus preferentially utilizes iron of heme origin, whose availability is the consequence of erythrocyte hemolysins produced by the organism.

Source: Skaar EP, et al. Iron-Source Preference of Staphylococcus aureus Infections. Science. 2004;1626-1628.

Skaar and colleagues at the University of Chicago subcultured iron-starved S. aureus into a chemically-defined medium supplement with equimolar amounts of [54Fe] hemin and [57Fe] transferrin, in order to determine which iron source was preferred by this pathogen. Analysis of organisms sampled over time demonstrated a significant (up to 5-fold) enrichment in the ratio of heme Fe to transferrin Fe, as compared to the ratio in the nutrient medium. Skaar et al also identified a heme transport system in S. aureus consisting of 3 genes with homology to known heme transporter genes of Yersinia enterocolitica and Corynebacterium diphtheriae.

Comment by Stan Deresinski, MD, FACP

Sequestration of iron is an important element of the host defense against bacterial infection, for the very reason that infecting pathogens require iron for growth and virulence. Since free iron is present in almost non-existent concentrations in plasma, the 2 major potential host sources of iron are heme and transferrin, the transporter protein. Bacteria acquire iron from their environment by expression of receptors specific for heme or transferrin iron, and/or by secretion of siderophores that can remove iron from transferrin with subsequent importation of the ironsiderophore complex into the bacterium. Heme, on the other hand, is itself sequestered within erythrocytes, and is not directly available. S. aureus, however, produces a number of hemolysins that disrupt function of the erythrocyte membrane, leading to cellular lysis and release of hemoglobin. Although the mechanisms are not strictly defined, heme is then released from its globin partner, allowing its importation into the bacterial pathogen, with release of iron from heme.

Further analysis by Skaar et al found that this iron of heme origin is critical to the virulence of experimental S. aureus infection during its early phase.

Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.