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.
© 2010 S. Karger AG, Basel
- Bacterial infections
- Host defense
- Staphylococcus aureus
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Dr. Frank R. DeLeo
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories
National Institute of Allergy and Infectious Diseases, National Institutes of Health
903 South 4th Street, Hamilton, MT 59840 (USA)
Tel. +1 406 363 9448, Fax +1 406 363 9394, E-Mail email@example.com
S.D.K. and K.R.B. contributed equally to this paper.
Received: January 28, 2010
Accepted after revision: April 13, 2010
Published online: June 26, 2010
Number of Print Pages : 16
Number of Figures : 10, Number of Tables : 0, Number of References : 41
Additional supplementary material is available online - Number of Parts : 2
Journal of Innate Immunity
Vol. 2, No. 6, Year 2010 (Cover Date: October 2010)
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