Iron regulated surface determinant (Isd) proteins of Staphylococcus lugdunensis.

Staphylococcus lugdunensis is the only species of coagulase negative staphylococcus with a locus encoding iron regulated surface determinant (Isd) proteins. In S. aureus the Isd proteins capture haem from haemoglobin, transfer it across the wall to a membrane-bound transporter which delivers it into the cytoplasm where haem oxygenases release iron. The Isd proteins of S. lugdunensis are expressed under iron-restricted conditions. We propose that S. lugdunensis IsdB and IsdC proteins perform the same functions as those of S. aureus. S. lugdunensis IsdB is the only haemoglobin receptor within the isd locus. It specifically binds human haemoglobin with a K(D) of 23 nM and transfers haem on IsdC. IsdB expression promotes bacterial growth in an iron-limited medium containing human haemoglobin but not mouse haemoglobin. This correlates with weak binding of IsdB to mouse haemoglobin in vitro. Unlike IsdB and IsdC, IsdJ and IsdK are not sorted to the cell wall in S. lugdunensis. In contrast, IsdJ expressed in S. aureus and Lactococcus lactis is anchored to peptidoglycan, suggesting that S. lugdunensis sortases may differ in signal recognition or could be defective. IsdJ and IsdK are present in the culture supernatant suggesting they could acquire haem from the external milieu. The IsdA protein of S. aureus protects bacteria from bactericidal lipids due to its hydrophilic C-terminal domain. IsdJ has a similar region and protected S. aureus and L. lactis as efficiently as IsdA but, possibly due to its location, was less effective in its natural host.