title: Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, Tennessee 37232-2363, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
authors.forename: William J
authors.initials: WJ
authors.lastname: Mason
authors.forename: M Indriati
authors.initials: MI
authors.lastname: Hood
authors.forename: Brian D
authors.initials: BD
authors.lastname: Corbin
authors.forename: Federico C
authors.initials: FC
authors.lastname: Beasley
authors.forename: Kelsi L
authors.initials: KL
authors.lastname: Anderson
authors.forename: Devin L
authors.initials: DL
authors.lastname: Stauff
authors.forename: W Hayes
authors.initials: WH
authors.lastname: McDonald
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zimmerman
authors.forename: David B
authors.initials: DB
authors.lastname: Friedman
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011023:Pneumonia, Staphylococcal / Q000382:microbiology*; D020543:Proteome / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity* / Q000502:physiology; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D012097:Repressor Proteins; D037521:Virulence Factors; C068477:ferric uptake regulating proteins, bacterial