An Iron-Regulated Sortase Anchors a Class of Surface Protein during Staphylococcus aureus Pathogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-02, Vol.99 (4), p.2293-2298
• Main Authors: Mazmanian, Sarkis K., Ton-That, Hung, Su, Kenneth, Schneewind, Olaf
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Motifs; Amino Acid Sequence; Aminoacyltransferases - metabolism; Bacteria; Bacterial Proteins - metabolism; Biological Sciences; Cell Wall - metabolism; Cell walls; Cysteine Endopeptidases; Enzymes; Infections; Iron - metabolism; isd gene; Membrane proteins; Microbiology; Molecular Sequence Data; Mutation; Open reading frames; Operons; Pathogenesis; Pathogens; Peptides - chemistry; Peptides - metabolism; Plasmids - metabolism; Protein Binding; Proteins; Repressor Proteins - metabolism; Sortase; SrtA protein; srtB gene; SrtB protein; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - pathogenicity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.032523999

Sortase (SrtA), an enzyme that anchors surface proteins to the cell wall of Gram-positive bacteria, cleaves sorting signals at the LPXTG motif. We have identified a second sortase (SrtB) in the Gram-positive pathogen Staphylococcus aureus that is required for anchoring of a surface protein with a NPQTN motif. Purified SrtB cleaves NPQTN-bearing peptides in vitro, and a srtB mutant is defective in the persistence of animal infections. srtB is part of an iron-regulated locus called iron-responsive surface determinants (isd), which also contains a ferrichrome transporter and surface proteins with NPQTN and LPXTG motifs. Cell wall-anchored surface proteins and the isd locus seem involved in a novel mechanism of iron acquisition that is important for bacterial pathogenesis.