Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia.

Torres VJ, Attia AS, Mason WJ, Hood MI, Corbin BD, Beasley FC, Anderson KL, Stauff DL, McDonald WH, Zimmerman LJ, Friedman DB, Heinrichs DE, Dunman PM, Skaar EP
Infect Immun. 2010 78 (4): 1618-28

PMID: 20100857 · PMCID: PMC2849423 · DOI:10.1128/IAI.01423-09

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.

MeSH Terms (17)

Animals Bacterial Proteins Chromatography, Liquid Disease Models, Animal Electrophoresis, Gel, Two-Dimensional Female Gene Expression Profiling Gene Expression Regulation, Bacterial Gene Knockout Techniques Mass Spectrometry Mice Mice, Inbred C57BL Pneumonia, Staphylococcal Proteome Repressor Proteins Staphylococcus aureus Virulence Factors

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