Characterization of a new cytotoxin that contributes to Staphylococcus aureus pathogenesis
Article first published online: 13 DEC 2010
© 2010 Blackwell Publishing Ltd
Volume 79, Issue 3, pages 814–825, February 2011
How to Cite
DuMont, A. L., Nygaard, T. K., Watkins, R. L., Smith, A., Kozhaya, L., Kreiswirth, B. N., Shopsin, B., Unutmaz, D., Voyich, J. M. and Torres, V. J. (2011), Characterization of a new cytotoxin that contributes to Staphylococcus aureus pathogenesis. Molecular Microbiology, 79: 814–825. doi: 10.1111/j.1365-2958.2010.07490.x
- Issue published online: 24 JAN 2011
- Article first published online: 13 DEC 2010
- Accepted manuscript online: 2 DEC 2010 03:26AM EST
- Accepted 26 November, 2010.
Staphylococcus aureus is an important pathogen that continues to be a significant global health threat because of the prevalence of methicillin-resistant S. aureus strains (MRSA). The pathogenesis of this organism is partly attributed to the production of a large repertoire of cytotoxins that target and kill innate immune cells, which provide the first line of defence against S. aureus infection. Here we demonstrate that leukocidin A/B (LukAB) is required and sufficient for the ability of S. aureus, including MRSA, to kill human neutrophils, macrophages and dendritic cells. LukAB targets the plasma membrane of host cells resulting in cellular swelling and subsequent cell death. We found that S. aureus lacking lukAB are severely impaired in their ability to kill phagocytes during bacteria–phagocyte interaction, which in turn renders the lukAB-negative staphylococci more susceptible to killing by neutrophils. Notably, we show that lukAB is expressed in vivo within abscesses in a murine infection model and that it contributes significantly to pathogenesis of MRSA in an animal host. Collectively, these results extend our understanding of how S. aureus avoids phagocyte-mediated clearance, and underscore LukAB as an important factor that contributes to staphylococcal pathogenesis.