<i>Staphylococcus aureus</i> fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia

Torres, V. J., A. S. Attia, W. J. Mason, M. I. Hood, B. D. Corbin, F. C. Beasley, K. L. Anderson, D. L. Stauff, W. H. McDonald, L. J. Zimmerman, et al., "Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia", Infection and immunity, 2010/01/27, vol. 78, no. 4, pp. 1618-28, Apr, 2010.


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.


Torres, Victor JAttia, Ahmed SMason, William JHood, M IndriatiCorbin, Brian DBeasley, Federico CAnderson, Kelsi LStauff, Devin LMcDonald, W HayesZimmerman, Lisa JFriedman, David BHeinrichs, David EDunman, Paul MSkaar, Eric PAI071487/AI/NIAID NIH HHS/AI073780/AI/NIAID NIH HHS/AI073843/AI/NIAID NIH HHS/AI074278/AI/NIAID NIH HHS/AI69233/AI/NIAID NIH HHS/T32 AI-07474-13/AI/NIAID NIH HHS/T32 GM07347/GM/NIGMS NIH HHS/T32 HL069765/HL/NHLBI NIH HHS/U54 AI057157/AI/NIAID NIH HHS/Infect Immun. 2010 Apr;78(4):1618-28. doi: 10.1128/IAI.01423-09. Epub 2010 Jan 25.

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