A Heme Relay from Hemoglobin to a Regulator of Siderophore Production

The Isd cluster of Staphylococcus aureus encodes seven genes to enable growth on heme or hemoglobin (Hb) as a sole iron source. IsdB is a receptor on the bacterial surface that binds Hb and extracts heme. IsdB is highly expressed by the S. aureus in blood and tissue infection models, indicating a key role of this receptor in bacterial virulence. From IsdB, heme is relayed through the cell wall by the Isd system into the cytosol to SbnI, a regulator for the production of the siderophore stapyloferrin B. Support for a mechanism of rapid heme relay by ligand exchange is achieved through determination of crystal structures, heme-transfer kinetics, and microbial genetics. These proteins are part of a growing network of proteins that shuttle heme in the within cell to limit heme toxicity.