Staphylococcus aureus Leukocidins Target Endothelial DARC to Cause Lethality in Mice

Cell Host & Microbe
Ashira LubkinVictor J Torres

Abstract

The pathogenesis of Staphylococcus aureus is thought to depend on the production of pore-forming leukocidins that kill leukocytes and lyse erythrocytes. Two leukocidins, Leukocidin ED (LukED) and γ-Hemolysin AB (HlgAB), are necessary and sufficient to kill mice upon infection and toxin challenge. We demonstrate that LukED and HlgAB cause vascular congestion and derangements in vascular fluid distribution that rapidly cause death in mice. The Duffy antigen receptor for chemokines (DARC) on endothelial cells, rather than leukocytes or erythrocytes, is the critical target for lethality. Consistent with this, LukED and HlgAB injure primary human endothelial cells in a DARC-dependent manner, and mice with DARC-deficient endothelial cells are resistant to toxin-mediated lethality. During bloodstream infection in mice, DARC targeting by S. aureus causes increased tissue damage, organ dysfunction, and host death. The potential for S. aureus leukocidins to manipulate vascular integrity highlights the importance of these virulence factors.

Citations

Feb 6, 2020·Infection and Immunity·David N HernandezGregg J Silverman
Jul 1, 2020·The Journal of Experimental Medicine·Kayan TamVictor J Torres
Mar 7, 2019·Nature Reviews. Microbiology·Andrea du Toit
Oct 15, 2020·The Journal of Biological Chemistry·Marilyn T VasquezVictor J Torres
Jan 18, 2021·The Journal of Biological Chemistry·Marilyn T VasquezVictor J Torres

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR & Staphylococcus

CRISPR-Cas system enables the editing of genes to create or correct mutations. Staphylococci are associated with life-threatening infections in hospitals, as well as the community. Here is the latest research on how CRISPR-Cas system can be used for treatment of Staphylococcal infections.