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Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses.

ABSTRACT: 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 ?Ecb?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 ?Ecb?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.

SUBMITTER: Jongerius I

PROVIDER: S-EPMC3357151 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses.

Jongerius Ilse I von Köckritz-Blickwede Maren M Horsburgh Malcolm J MJ Ruyken Maartje M Nizet Victor V Rooijakkers Suzan H M SH

Journal of innate immunity 20120207 3

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 bot ...[more]

PMID: 22327617

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Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses.

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Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses.

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