In Staphylococcus aureus, Fur Is an Interactive Regulator with PerR, Contributes to Virulence, and Is Necessary for Oxidative Stress Resistance through Positive Regulation of Catalase and Iron Homeostasis
AUTOR(ES)
Horsburgh, Malcolm J.
FONTE
American Society for Microbiology
RESUMO
The Staphylococcus aureus genome encodes three ferric uptake repressor (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of Fur in S. aureus, we inactivated the fur gene by allelic replacement using a tetracycline resistance cassette, creating strain MJH010 (fur). The mutant had a growth defect in rich medium, and this defect was exacerbated in metal-depleted CL medium. This growth defect was partially suppressed by manganous ion, a metal ion with known antioxidant properties. This suggests that the fur mutation leads to an oxidative stress condition. Indeed, MJH010 (fur) has reduced levels of catalase activity resulting from decreased katA transcription. Using a katA-lacZ fusion we have determined that Fur functions, either directly or indirectly, as an iron-dependent positive regulator of katA expression. Transcription of katA is coregulated by Fur and PerR, since in MJH010 (fur) transcription was still repressed by manganese while transcription in MJH201 (fur perR) was unresponsive to the presence of iron or manganese. Siderophore biosynthesis was repressed by iron in 8325-4 (wild-type) but in MJH010 (fur) was constitutive. A number of putative Fur-regulated genes were identified in the incomplete genome databases using known S. aureus Fur box sequences. Of those tested, the sstABCD and sirABC operons and the fhuD2 and orf4 genes were found to have Fur-regulated expression. MJH010 (fur) was attenuated (P < 0.04) in a murine skin abscess model of infection, as was double-mutant MJH201 (fur perR) (P < 0.03). This demonstrates the importance in vivo of iron homeostasis and oxidative stress resistance regulation in S. aureus.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=94901Documentos Relacionados
- The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes
- PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus
- Regulation of the Bacillus subtilis fur and perR Genes by PerR: Not All Members of the PerR Regulon Are Peroxide Inducible
- Campylobacter jejuni Contains Two Fur Homologs: Characterization of Iron-Responsive Regulation of Peroxide Stress Defense Genes by the PerR Repressor
- The Staphylococcal Ferritins Are Differentially Regulated in Response to Iron and Manganese and via PerR and Fur