Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 28, Pages 7416-7421Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1721949115
Keywords
biofilms; MRSA; neutrophil extracellular traps; leukocidins
Categories
Funding
- National Institute of Nursing Research/National Institute of Health (NIH) [R01NR013898]
- Cystic Fibrosis Foundation [WOZNIA16GO]
- National Institutes of Allergy and Infectious Diseases [AI099394, AI105129]
- Netherlands Organization for Scientific Research
- NIH [P30 CA16058]
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Bacterial biofilms efficiently evade immune defenses, greatly complicating the prognosis of chronic infections. How methicillin-resistant Staphylococcus aureus (MRSA) biofilms evade host immune defenses is largely unknown. This study describes some of the major mechanisms required for S. aureus biofilms to evade the innate immune response and provides evidence of key virulence factors required for survival and persistence of bacteria during chronic infections. Neutrophils are the most abundant white blood cells in circulation, playing crucial roles in the control and elimination of bacterial pathogens. Specifically, here we show that, unlike single-celled populations, S. aureus biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET) formation through the combined activity of leukocidins Panton-Valentine leukocidin and gamma-hemolysin AB. By eliciting this response, S. aureus was able to persist, as the antimicrobial activity of released NETs was ineffective at clearing biofilm bacteria. Indeed, these studies suggest that NETs could inadvertently potentiate biofilm infections. Last, chronic infection in a porcine burn wound model clearly demonstrated that leukocidins are required for NETosis and facilitate bacterial survival in vivo.
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