Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo
Article first published online: 20 DEC 2011
© 2011 Blackwell Publishing Ltd
Volume 83, Issue 2, pages 423–435, January 2012
How to Cite
Alonzo III, F., Benson, M. A., Chen, J., Novick, R. P., Shopsin, B. and Torres, V. J. (2012), Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo. Molecular Microbiology, 83: 423–435. doi: 10.1111/j.1365-2958.2011.07942.x
- Issue published online: 11 JAN 2012
- Article first published online: 20 DEC 2011
- Accepted manuscript online: 6 DEC 2011 06:27AM EST
- Accepted 30 November, 2011.
Bloodstream infection with Staphylococcus aureus is common and can be fatal. However, virulence factors that contribute to lethality in S. aureus bloodstream infection are poorly defined. We discovered that LukED, a commonly overlooked leucotoxin, is critical for S. aureus bloodstream infection in mice. We also determined that LukED promotes S. aureus replication in vivo by directly killing phagocytes recruited to sites of haematogenously seeded tissue. Furthermore, we established that murine neutrophils are the primary target of LukED, as the greater virulence of wild-type S. aureus compared with a lukED mutant was abrogated by depleting neutrophils. The in vivo toxicity of LukED towards murine phagocytes is unique among S. aureus leucotoxins, implying its crucial role in pathogenesis. Moreover, the tropism of LukED for murine phagocytes highlights the utility of murine models to study LukED pathobiology, including development and testing of strategies to inhibit toxin activity and control bacterial infection.