Wall Teichoic Acid Mediates Staphylococcus aureus Binding to Endothelial Cells via the Scavenger Receptor LOX-1

ACS Infect Dis. 2023 Nov 10;9(11):2133-2140. doi: 10.1021/acsinfecdis.3c00252. Epub 2023 Nov 1.

Abstract

The success of Staphylococcus aureus as a major cause for endovascular infections depends on effective interactions with blood-vessel walls. We have previously shown that S. aureus uses its wall teichoic acid (WTA), a surface glycopolymer, to attach to endothelial cells. However, the endothelial WTA receptor remained unknown. We show here that the endothelial oxidized low-density lipoprotein receptor 1 (LOX-1) interacts with S. aureus WTA and permits effective binding of S. aureus to human endothelial cells. Purified LOX-1 bound to isolated S. aureus WTA. Ectopic LOX-1 expression led to increased binding of S. aureus wild type but not of a WTA-deficient mutant to a cell line, and LOX-1 blockage prevented S. aureus binding to endothelial cells. Moreover, WTA and LOX-1 expression levels correlated with the efficacy of the S. aureus-endothelial interaction. Thus, LOX-1 is an endothelial ligand for S. aureus, whose blockage may help to prevent or treat severe endovascular infections.

Keywords: LOX-1; Staphylococcus aureus; bloodstream infections; scavenger receptor; sepsis; wall teichoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells
  • Humans
  • Receptors, Scavenger / metabolism
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism
  • Staphylococcal Infections*
  • Staphylococcus aureus* / genetics
  • Staphylococcus aureus* / metabolism
  • Teichoic Acids / metabolism

Substances

  • Teichoic Acids
  • Receptors, Scavenger
  • Scavenger Receptors, Class E