並列タイトル等Single mutations in BraRS confer high resistance against nisin A in Staphylococcus aureus.
学位博士(歯学)
Doctor of Philosophy in Dental Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Nisin A is a lantibiotic produced by Lactococcus lactis that is widely used as a food preservative. In Staphylococcus aureus, the BraRS two‐component system (TCS) senses nisin A and regulates the expression of the ABC transporter VraDE, which is responsible for nisin A resistance. In this study, we exposed S. aureus to a sub‐minimum inhibition concentration of nisin A and obtained three spontaneous mutants that were highly resistant to this lantibiotic, designated as SAN (S. aureus nisin resistant) 1, SAN8, and SAN87. In the wild‐type S. aureus strain, VraDE expression was induced by nisin A. In contrast, SAN8 and SAN87 showed constitutively high VraDE expression, even in the absence of nisin A, while SAN1 showed higher BraRS expression, which resulted in high VraDE expression in the presence of nisin A. We identified a single mutation in the promoter region of braXRS in SAN1, whereas SAN8 and SAN87 had single mutations in braR and braS, respectively. Interestingly, even the unphosphorylated form of the mutant BraR protein induced VraDE expression. These results indicate that conformational changes in BraS or BraR resulting from the point mutations may result in the constitutive expression of VraDE, allowing S. aureus to adapt to high concentrations of nisin A.
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）