Journal
JOURNAL OF INNATE IMMUNITY
Volume 4, Issue 3, Pages 301-311Publisher
KARGER
DOI: 10.1159/000334604
Keywords
Neutrophils; Complement; Fibrinogen; Immune evasion; Staphylococci
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Funding
- Deutsche Akademie der Naturforscher Leopoldina [BMBF-LPD9901/8-187]
- NIH [AI077780]
- Netherlands Organization of Scientific Research
- European Organization of Molecular Biology (EMBO) [ALTF 382-2008]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI077780] Funding Source: NIH RePORTER
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Staphylococcus aureus is a leading human pathogen that causes a large variety of diseases. In vitro studies have shown that S. aureus secretes several small proteins that block specific elements of the host innate immune system, but their role in bacterial pathogenicity is unknown. For instance, the extracellular complement-binding protein (Ecb) impairs complement activation by binding to the C3d domain of C3. Its homolog, the extracellular fibrinogen-binding protein (Efb), is known to block both complement activation and neutrophil adhesion to fibrinogen. Here, we show that targeted inactivation of the genes encoding Ecb and Efb strongly attenuates S. aureus virulence in a murine infection model: mice experienced significantly higher mortality rates upon intravenous infection with wild-type bacteria (79%) than with an isogenic Delta Ecb Delta Efb mutant (21%). In addition, Ecb and Efb are both required for staphylococcal persistence in host tissues and abscess formation in the kidneys (27% for wild-type vs. 7% for the Delta Ecb Delta Efb mutant). During staphylococcal pneumonia, Ecb and Efb together promote bacterial survival in the lungs (p = 0.03) and block neutrophil influx into the lungs. Thus, Ecb and Efb are essential to S. aureus virulence in vivo and could be attractive targets in future vaccine development efforts. Copyright (C) 2012 S. Karger AG, Basel
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