Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus

Scott D. Kobayashi, Kevin R. Braughton, Amy M. Palazzolo-Ballance, Adam D. Kennedy, Elizabeth Sampaio, Ervand Kristosturyan, Adeline R. Whitney, Daniel E. Sturdevant, David W. Dorward, Steven M. Holland, Barry N. Kreiswirth, James M. Musser, Frank R. DeLeo

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Mechanisms underlying the enhanced virulence phenotype of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are incompletely defined, but presumably include evasion of killing by human polymorphonuclear leukocytes (PMNs or neutrophils). To better understand this phenomenon, we investigated the basis of rapid PMN lysis after phagocytosis of USA300, a prominent CA-MRSA strain. Survival of USA300 clinical isolates after phagocytosis ultimately resulted in neutrophil lysis. PMNs containing ingested USA300 underwent morphological changes consistent with apoptosis, but lysed rapidly thereafter (within 6 h), whereas cells undergoing FAS-mediated apoptosis or phagocytosis-induced cell death remained intact. Phagosome membranes remained intact until the point of PMN destruction, suggesting lysis was not caused by escape of S. aureus from phagosomes or the cytolytic action of pore-forming toxins. Microarray analysis of the PMN transcriptome after phagocytosis of representative community-associated S. aureus and healthcare-associated MRSA strains revealed changes unique to community-associated S. aureus strains, such as upregulation of transcripts involved in regulation of calcium homeostasis. Collectively, the data suggest that neutrophil destruction after phagocytosis of USA300 is in part a form of programmed necrosis rather than direct lysis by S. aureus pore-forming toxins. We propose that the ability of CA-MRSA strains to induce programmed necrosis of neutrophils is a component of enhanced virulence.

Original languageEnglish (US)
Pages (from-to)560-575
Number of pages16
JournalJournal of Innate Immunity
Volume2
Issue number6
DOIs
StatePublished - Oct 2010

Keywords

  • Bacterial infections
  • Host defense
  • Neutrophils
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Immunology and Allergy

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