The lipoprotein components of the Isd and Hts transport systems are dispensable for acquisition of heme by Staphylococcus aureus

Heme is a key molecule for Staphylococcus aureus and is involved in many aspects of oxidative metabolism. Crucially, heme is required for the activity of cytochromes of the electron transport chain. Staphylococcus aureus is able to obtain heme either through biosynthesis or through acquisition from the host. Clinically persistent 'small colony variant' (SCV) forms of S. aureus are frequently deficient for heme biosynthesis, and disruption of the hemB gene produces stable heme-auxotrophic strains that reproduce many SCV phenotypes. We sought to address the role of heme transport in SCVs by deleting components of the two described heme import systems, the iron-regulated surface determinant (Isd) and heme transport system (Hts) in wild-type S. aureus and hemB mutant backgrounds. Analysis of the growth of S. aureus hemB strains either singly or doubly deficient in isdE and htsA in the presence and absence of heme or hemoglobin revealed that S. aureus is able to obtain exogenous heme in the absence of these transporter components. These data suggest the presence of additional, as yet unidentified transporter components that enable S. aureus to internalize exogenous heme and contradict the proposed model that IsdE can transfer heme to the HtsBC permease.