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.

在寻找新的致病机制的过程中，我发现-溶血素，一种来自金黄色葡萄球菌的红细胞溶解毒素，会损害人的角化细胞。这一结果提示该毒素可能与金黄色葡萄球菌感染导致的特应性皮炎有关，这一发现可能有助于进一步了解该疾病及其治疗方法。我还参与了50多年前从放线菌中分离出的新霉素的再评价研究，发现该物质特异性抑制不再被氟喹诺酮类药物灭活的突变细菌DNA回旋酶的功能，而耐新霉素的DNA回旋酶则获得了氟喹诺酮类药物的敏感性，表明氟喹诺酮类药物和新霉素具有互补的功能。这种对抗已知抗生素的物质被称为“反向抗生素”，有望开启抗生素化疗的新时代。值得注意的是，上述结果是与原本不在这个项目中的科学家合作研究获得的。

项目成果

黄色ブドウ球菌MHC様分子が貪食などの宿主免疫系に及ぼす影響について(MHC analogues found in Staphylococcus aureus affect phagocytosis and other immune responses by human whit e-blood cells)

金黄色葡萄球菌中发现的 MHC 类似物影响人类白细胞的吞噬作用和其他免疫反应

• 发表时间: 2011
• 期刊: 順天堂医学
• 作者: 関根美和;他
• 通讯作者: 他

MHC analogues found in S.aureus affect phagocytosis and other immune responses

金黄色葡萄球菌中发现的 MHC 类似物影响吞噬作用和其他免疫反应

• 发表时间: 2012
• 作者: M.Sekine;T.Baba;Y.Katayama;K.Hiramatsu
• 通讯作者: K.Hiramatsu

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

• DOI: 10.1159/000343895
• 发表时间: 2013-01-01
• 期刊: JOURNAL OF INNATE IMMUNITY
• 影响因子: 5.3
• 作者: Fukuda, Minoru;Ushio, Hiroko;Ogawa, Hideoki
• 通讯作者: Ogawa, Hideoki

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

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