Passage of Heme-Iron Across the Envelope of Staphylococcus aureus
Sarkis K. Mazmanian,12*
Eric P. Skaar,12*
Andrew H. Gaspar,12
Munir Humayun,3
Piotr Gornicki,2
Joanna Jelenska,2
Andrzej Joachmiak,4
Dominique M. Missiakas,15
Olaf Schneewind12
The cell wall envelope of Gram-positive pathogens
functions as a scaffold for the attachment of virulence factors and as
a sieve that prevents diffusion of molecules. Here the isd
genes (iron-regulated surface determinant) of Staphylococcus
aureus were found to encode factors responsible for hemoglobin
binding and passage of heme-iron to the cytoplasm, where it acts as an essential nutrient. Heme-iron passage required two sortases that tether
Isd proteins to unique locations within the cell wall. Thus, Isd
appears to act as an import apparatus that uses cell wall-anchored
proteins to relay heme-iron across the bacterial envelope.
1 Committee on Microbiology,
2 Department of Molecular Genetics and Cell Biology,
3 Department of Geophysical Sciences,
5 Department of Biochemistry and Molecular Biology,
University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
4 Bioscience Division, Structural Biology Center,
Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
oschnee{at}delphi.bsd.uchicago.edu