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Identified virulence factors of Staphylococcus: Iron uptake


Isd  

Related genes: isdA; isdB; isdC; isdD; isdE; isdF; isdG; srtB;
Keywords: Iron uptake; Heme uptake;
Figures:
Genomic arrangement of the genes encoding the Isd system


Heme acquisition is mediated by the Isd system. IsdH binds the hemoglobin-haptoglobin complex and IsdB binds hemoglobin. Heme is passed through the NEAr iron Transporter (NEAT) domains of IsdH (N1-N3), IsdB (N1-N2), IsdA, and IsdC. Heme can also be passed from IsdH or IsdB directly to the IsdE heme-receptor lipoprotein. Heme transport across the membrane occurs through either the IsdDF or the HtsBC permeases. Once in the cytoplasm heme is a substrate for the heme-degrading enzymes IsdG and IsdI. S. aureus degradation of heme leads to the release of iron and the production of staphylobilin (From: Hammer ND, et al., 2011. Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol 65:129-147.).

Mechanism:
Surface exposed protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme usually associated with glycolysis, is a transferrin receptor involved in stripping iron off transferrin.
isd genes (iron-regulated surface determinant) encode factors for hemoglobin binding and passage of heme-iron to the cytoplasm:
hemoglobin binds on IsdB. Heme is removed from hemoglobin (IsdA and IsdB) and transferred to cell wall (IsdC) and membrane translocation factors (IsdD, IsdE, and IsdF). IsdG is involved in removing iron from heme.
S. aureus also has a siderophore-based mechanism for iron acquisition.
References:
Mazmanian SK, et al., 1999. Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285(5428):760-763.
Mazmanian SK, et al., 2002. An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc. Natl. Acad. Sci. USA. 99(4):2293-2298.
Taylor JM, Heinrichs DE, 2002. Transferrin binding in Staphylococcus aureus: involvement of a cell wall-anchored protein. Mol. Microbiol. 43(6):1603-1614.
Mazmanian SK, et al., 2003. Passage of heme-iron across the envelope of Staphylococcus aureus. Science 299(5608):906-909.
Skaar EP, et al., 2004. IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus. J. Biol. Chem. 279(1):436-443.
Skaar EP, Schneewind O, 2004. Iron-regulated surface determinants (Isd) of Staphylococcus aureus: stealing iron from heme. Microbes Infect. 6(4):390-397.








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