Bacillithiol has a role in Fe–S cluster biogenesis in Staphylococcus aureus. Issue 2 (30th July 2015)

• Record Type: Journal Article
• Authors: Rosario‐Cruz, Zuelay; Chahal, Harsimranjit K.; Mike, Laura A.; Skaar, Eric P.; Boyd, Jeffrey M.
• Is Part Of: Molecular microbiology. Volume 98:Issue 2(2015)
• Page Start: 218
• Page End: 242
• Publication Date: 2015-07-30
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13115
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>S</italic> <italic>taphylococcus aureus</italic> does not produce the low‐molecular‐weight (LMW) thiol glutathione, but it does produce the LMW thiol bacillithiol (BSH). To better understand the roles that BSH plays in staphylococcal metabolism, we constructed and examined strains lacking BSH. Phenotypic analysis found that the BSH‐deficient strains cultured either aerobically or anaerobically had growth defects that were alleviated by the addition of exogenous iron (Fe) or the amino acids leucine and isoleucine. The activities of the iron–sulfur (Fe–S) cluster‐dependent enzymes LeuCD and IlvD, which are required for the biosynthesis of leucine and isoleucine, were decreased in strains lacking BSH. The BSH‐deficient cells also had decreased aconitase and glutamate synthase activities, suggesting a general defect in Fe–S cluster biogenesis. The phenotypes of the BSH‐deficient strains were exacerbated in strains lacking the Fe–S cluster carrier Nfu and partially suppressed by multicopy expression of either <italic>sufA</italic> or <italic>nfu</italic>, suggesting functional overlap between BSH and Fe–S carrier proteins. Biochemical analysis found that SufA bound and transferred Fe–S clusters to apo‐aconitase, verifying that it serves as an Fe–S cluster carrier. The results presented are consistent with the hypothesis that BSH has roles in Fe homeostasis and the carriage of Fe–S clusters to apo‐proteins in <italic>S</italic><italic>. aureus</italic>.</p> </abstract>