Nfu facilitates the maturation of iron‐sulfur proteins and participates in virulence in Staphylococcus aureus. Issue 3 (20th December 2014)

• Record Type: Journal Article
• Authors: Mashruwala, Ameya A.; Pang, Yun Y.; Rosario‐Cruz, Zuelay; Chahal, Harsimranjit K.; Benson, Meredith A.; Mike, Laura A.; Skaar, Eric P.; Torres, Victor J.; Nauseef, William M.; Boyd, Jeffrey M.
• Is Part Of: Molecular microbiology. Volume 95:Issue 3(2015)
• Page Start: 383
• Page End: 409
• Publication Date: 2014-12-20
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12860
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The acquisition and metabolism of iron (Fe) by the human pathogen <italic>S</italic><italic>taphylococcus aureus</italic> is critical for disease progression. <italic>S</italic><italic>. aureus</italic> 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 <italic>S</italic><italic>. aureus</italic> to metabolize Fe‐S clusters. We identified that <italic>S</italic><italic>. aureus</italic> utilizes the Suf biosynthetic system to synthesize Fe‐S clusters and we provide genetic evidence suggesting that the <italic>suf</italic><italic>U</italic> and <italic>suf</italic><italic>B</italic> 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 <italic>nfu</italic> gene negatively impacts staphylococcal physiology and pathogenicity. A <italic>nfu</italic> 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 <italic>ex vivo</italic> findings, a <italic>nfu</italic> 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.</p> </abstract>