Staphylococcus aureus skin colonization is mediated by SasG lectin variation
Krista B. Mills,
Joseph J. Maciag,
Can Wang,
John A. Crawford,
Timothy J. Enroth,
Klara C. Keim,
Yves F. Dufrêne,
D. Ashley Robinson,
Paul D. Fey,
Andrew B. Herr,
Alexander R. Horswill
Affiliations
Krista B. Mills
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Joseph J. Maciag
Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Can Wang
Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve, Belgium
John A. Crawford
Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
Timothy J. Enroth
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Klara C. Keim
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Yves F. Dufrêne
Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve, Belgium
D. Ashley Robinson
Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA; Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA
Paul D. Fey
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
Andrew B. Herr
Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Alexander R. Horswill
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Veterans Affairs, VA Eastern Colorado Healthcare System, Aurora, CO, USA; Corresponding author
Summary: Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization.
