Staphylococcus aureus leukocidins target endothelial DARC to cause lethality in mice
By Ashira Lubkin, Warren L. Lee, Francis Alonzo, Changsen Wang, Jason Aligo, M. Keller, N. Girgis, Tamara Reyes-Robles, Rita Chan, Aidan O’Malley and 21 more. 2019
39 citations recorded by the source corpus.
SUMMARY 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.
Subfields: Immunology, Immunology and Allergy, Infectious Diseases
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Citations in the corpus
- Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes (2020, methodology): “In fact, when LukED is injected intravenously, the toxin targets murine Darc on endothelial cells to cause rapid lethality through derangements in the distribution of vascular fluid (32).”