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

doi:10.1016/j.celrep.2024.114022

Staphylococcus aureus skin colonization is mediated by SasG lectin variation

Cell Rep. 2024 Apr 23;43(4):114022. doi: 10.1016/j.celrep.2024.114022. Epub 2024 Apr 2.

Authors

Affiliations

¹ Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
² Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
³ Louvain Institute of Biomolecular Science and Technology, UCLouvain, Louvain-la-Neuve, Belgium.
⁴ Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA.
⁵ 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.
⁶ Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
⁷ 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.
⁸ 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. Electronic address: [email protected].

PMID: 38568806
DOI: 10.1016/j.celrep.2024.114022

Abstract

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.

Keywords: Aap; CP: Microbiology; SasG; Staphylococcus aureus; Staphylococcus epidermidis; corneocytes; keratinocytes; skin.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Bacterial Adhesion*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Humans
Keratinocytes* / metabolism
Keratinocytes* / microbiology
Lectins / metabolism
Phylogeny
Protein Binding
Skin* / metabolism
Skin* / microbiology
Staphylococcus aureus* / metabolism

Substances

Lectins
Bacterial Proteins

Grants and funding

R01 AI162964/AI/NIAID NIH HHS/United States