Integrated analyses of virulence factors from Staphylococcus aureusaiming to pursue novel pathogenic mechanisms and chemotherapy based on new concept

金黄色葡萄球菌毒力因子综合分析，寻求新的致病机制及新理念化疗

• 批准号: 22590402
• 负责人: BABA Tadashi
• 金额: $ 2.83万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590402/
• 关键词: 黄色ブドウ球菌; 赤血球溶解毒素; β-ヘモリジン; ヒトケラチノサイト; アトピー性皮膚炎; nybomycin; キノロン; gyrase; ヒト皮膚角化細胞; バクテリオファージ; 病原性; ケラチノサイト; 病原性アイランド; 細胞毒性; 免疫細胞; 宿主特異性; MHC; TSLP; 好中球

On the way to pursue novel pathogenic mechanisms that can be candidates for targets of novel chemotherapy, I found ・-hemolysin, known as an erythrolytic toxin from Staphylococcus aureus, damages human keratinocytes. This result suggests that the toxin is presumably involved in atopic dermatitis that is worsened by S. aureus infection, and the finding may lead to further understanding of the disease and its therapy. I also played part in research on re-evaluation of nybomycin, that had been isolated from actinobacteria over 50 years ago, and showed that the substance specifically inhibits function of mutated bacterial DNA gyrase that was no longer inactivated by fluoroquinolones, whereas nybomycin-resistant DNA gyrase acquired fluoroquinolone susceptibility, indicating fluoroquinolones and nybomicin have mutually complementary functions. Such substance against known antibiotic was designated ‘reverse antibiotic’, being expected to open new era of antibiotic chemotherapy. It should be noted that the results described above were obtained cooperative researches with scientists who were originally out of this project.

在寻找可作为新型化疗靶点的新致病机制的过程中，我发现β-溶血素（一种来自金黄色葡萄球菌的溶红细胞毒素）会损害人类角质形成细胞。这一结果表明，该毒素可能与特应性皮炎有关。金黄色葡萄球菌感染使病情恶化，这一发现可能会导致对该疾病及其治疗的进一步了解。我还参与了重新评估的研究。尼博霉素是 50 多年前从放线菌中分离出来的，结果表明该物质特异性抑制突变细菌 DNA 旋转酶的功能，而该酶不再被氟喹诺酮类药物灭活，而耐博霉素耐药的 DNA 旋转酶获得了氟喹诺酮类药物敏感性，这表明氟喹诺酮类药物和尼博霉素具有相互影响。这种针对已知抗生素的互补功能被称为“反向抗生素”，有望开启抗生素新时代。值得注意的是，上述结果是与最初不属于该项目的科学家合作研究获得的。

项目成果

Antimicrobial activity of Nybomycin against Escherichia coli

Nybomycin 对大肠杆菌的抗菌活性

• 发表时间: 2013
• 作者: Y. Morimoto; M. Igarashi; T. Baba; K. Hiramatsu
• 通讯作者: K. Hiramatsu

毒素検出方法

毒素检测方法

• 发表时间: 2012

Beta-hemolysin promotes skin colonization by Staphylococcus aureus.

β-溶血素促进金黄色葡萄球菌在皮肤上定植。

• DOI: 10.1128/jb.01786-12
• 发表时间: 2013
• 影响因子: 3.2
• 作者: Katayama Y; Baba T; Sekine M; Fukuda M; Hiramatsu K.
• 通讯作者: Hiramatsu K.

新規化合物、DNAジャイレース阻害剤及びその用途

新化合物、DNA旋转酶抑制剂及其用途

• 发表时间: 2013

Expression and Functional Characterization of Retinoic Acid-Inducible Gene-I-Like Receptors of Mast Cells in Response to Viral Infection

肥大细胞视黄酸诱导基因 I 样受体响应病毒感染的表达和功能表征

• 发表时间: 2012
• 影响因子: 5.3
• 作者: Fukuda M; Ushio H; Kawasaki J; Niyonsaba F; Takeuchi M; Baba T; Hiramatsu K; Okumura K; Ogawa H
• 通讯作者: Ogawa H