| Autor: |
Zuelay Rosario-Cruz, William M. Nauseef, Laura A. Mike, Harsimranjit K. Chahal, Ameya A. Mashruwala, Victor J. Torres, Jeffrey M. Boyd, Meredith A. Benson, Eric P. Skaar, Yun Y. Pang |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Molecular Microbiology. 95:383-409 |
| ISSN: |
0950-382X |
| DOI: |
10.1111/mmi.12860 |
| Popis: |
The acquisition and metabolism of iron (Fe) by the human pathogen Staphylococcus aureus is critical for disease progression. S. aureus requires Fe to synthesize inorganic cofactors called iron-sulfur (Fe-S) clusters, which are required for functional Fe-S proteins. In this study we investigated the mechanisms utilized by S. aureus to metabolize Fe-S clusters. We identified that S. aureus utilizes the Suf biosynthetic system to synthesize Fe-S clusters and we provide genetic evidence suggesting that the sufU and sufB gene products are essential. Additional biochemical and genetic analyses identified Nfu as an Fe-S cluster carrier, which aids in the maturation of Fe-S proteins. We find that deletion of the nfu gene negatively impacts staphylococcal physiology and pathogenicity. A nfu mutant accumulates both increased intracellular non-incorporated Fe and endogenous reactive oxygen species (ROS) resulting in DNA damage. In addition, a strain lacking Nfu is sensitive to exogenously supplied ROS and reactive nitrogen species. Congruous with ex vivo findings, a nfu mutant strain is more susceptible to oxidative killing by human polymorphonuclear leukocytes and displays decreased tissue colonization in a murine model of infection. We conclude that Nfu is necessary for staphylococcal pathogenesis and establish Fe-S cluster metabolism as an attractive antimicrobial target. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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