4.4 Article

Staphylococcus aureus Fur Regulates the Expression of Virulence Factors That Contribute to the Pathogenesis of Pneumonia

Journal

INFECTION AND IMMUNITY
Volume 78, Issue 4, Pages 1618-1628

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.01423-09

Keywords

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Funding

  1. Vanderbilt University Medical Center development
  2. United States Public Health Service
  3. National Institute of Allergy and Infectious Diseases [AI69233, AI073843, AI071487, AI074278, T32 AI-07474-13, T32 HL069765, AI073780]
  4. NIH [U54 AI057157]
  5. Southeastern Regional Center of Excellence for Emerging Infections and Biodefense
  6. Wellcome Fund
  7. Canadian Institutes of Health Research
  8. University of Nebraska Medical Center
  9. American Heart Association [0535037N]
  10. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL069765] Funding Source: NIH RePORTER
  11. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [F32AI074278, U54AI057157, R01AI073843, T32AI007474, R01AI073780, F32AI071487, R01AI069233] Funding Source: NIH RePORTER
  12. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007347] Funding Source: NIH RePORTER

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The tremendous success of Staphylococcus aureus as a pathogen is due to the controlled expression of a diverse array of virulence factors. The effects of host environments on the expression of virulence factors and the mechanisms by which S. aureus adapts to colonize distinct host tissues are largely unknown. Vertebrates have evolved to sequester nutrient iron from invading bacteria, and iron availability is a signal that alerts pathogenic microorganisms when they enter the hostile host environment. Consistent with this, we report here that S. aureus senses alterations in the iron status via the ferric uptake regulator (Fur) and alters the abundance of a large number of virulence factors. These Fur-mediated changes protect S. aureus against killing by neutrophils, and Fur is required for full staphylococcal virulence in a murine model of infection. A potential mechanistic explanation for the impact of Fur on virulence is provided by the observation that Fur coordinates the reciprocal expression of cytolysins and a subset of immunomodulatory proteins. More specifically, S. aureus lacking fur exhibits decreased expression of immunomodulatory proteins and increased expression of cytolysins. These findings reveal that Fur is involved in initiating a regulatory program that organizes the expression of virulence factors during the pathogenesis of S. aureus pneumonia.

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