Staphylococcal leukocidins are pore-forming toxins that lyse leukocytes and red blood cells and cause host lethality. Lubkin et al. uncovered that those virulence factors also target endothelial cells to cause lethality. In a toxin challenge model, they showed that two leukocidins (leukocidin ED (LukED) and γ-haemolysin AB (HlgAB)) caused vascular dysfunction and death in mice. Importantly, they found that the toxins target the Duffy antigen receptor for chemokines (DARC; also known as ACKR1) on human and mouse endothelial cells rather than leukocytes or erythrocytes. They went on to show that targeting of DARC by LukED and HlgAB impairs vascular integrity, which leads to tissue damage and organ failure, and subsequent death during acute bloodstream infection in mice. By contrast, mice with Darc-deficient endothelial cells were resistant to toxin-mediated lethality.
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Original article
Lubkin, A. et al. Staphylococcus aureus leukocidins target endothelial DARC to cause lethality in mice. Cell Host Microbe https://doi.org/10.1016/j.chom.2019.01.015 (2019)
Further reading
Spaan, A. N., van Strijp, J. A. G. and Torres, V. J. Leukocidins: staphylococcal bi-component pore-forming toxins find their receptors. Nat. Rev. Microbiol. 15, 435–447 (2017)
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Toit, A.d. New targets for leukocidins. Nat Rev Microbiol 17, 266 (2019). https://doi.org/10.1038/s41579-019-0181-x
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DOI: https://doi.org/10.1038/s41579-019-0181-x
