| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-05-27 |
| タイトル |
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タイトル |
Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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言語 |
en |
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キーワード |
Bordetella |
| キーワード |
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言語 |
en |
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キーワード |
BvgAS |
| キーワード |
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言語 |
en |
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キーワード |
lonidamine |
| キーワード |
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言語 |
en |
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キーワード |
modulator |
| キーワード |
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言語 |
en |
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キーワード |
phase conversion |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Ota, Natsuko
Nishida, Takashi
Standley, Daron M.
Sherif, Aalaa Alrahman
岩野, 智
WEKO
35018
e-Rad_Researcher
10734832
| ja |
岩野, 智
宮崎大学
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| ja-Kana |
イワノ, サトシ
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| en |
Iwano, Satoshi
University of Miyazaki
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Search repository
Nugraha, Dendi Krisna
Ueno, Toshiya
Horiguchi, Yasuhiko
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
The Gram-negative bacteria Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory diseases in various mammals. They share the BvgAS two-component system, which regulates the phenotypic conversion between the virulent Bvg+ and avirulent Bvg– phases. In the BvgAS system, the sensor kinase BvgS senses environmental cues and transduces a phosphorelay signal to the response regulator BvgA, which leads to the expression of Bvg+ phase-specific genes, including virulence factor genes. Bacteria grown at 37°C exhibit the Bvg+ phenotype. In contrast, at lower than 26°C or in the presence of modulators, such as MgSO4 and nicotinic acid, the BvgAS system is inactivated, leading bacteria to the avirulent Bvg– phase. Therefore, effective modulators are expected to provide a therapeutic measure for Bordetella infection; however, no such modulators are currently available, and the mechanism by which modulators inactivate the BvgAS system is poorly understood. In the present study, we identified lonidamine as a novel modulator after screening an FDA-approved drug library using bacterial reporter systems with the Bvg+-specific and Bvg–-specific promoters. Lonidamine directly bound to the VFT2 domain of BvgS and inactivated the BvgAS system at concentrations as low as 50 nM, which was at least 2000- to 20,000-fold lower than the effective concentrations of known modulators. Lonidamine significantly reduced the adherence of B. pertussis to cultured cells but unexpectedly exacerbated bacterial colonization of the mouse nasal septum. These results provide insights into the structural requirements for BvgAS modulators and the role of Bvg phenotypes in the establishment of infection. |
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言語 |
en |
| 内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Citation: Natsuko Ota, Takashi Nishida, Daron M. Standley, Aalaa Alrahman Sherif, Satoshi Iwano, Dendi Krisna Nugraha, Toshiya Ueno, Yasuhiko Horiguchi, Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species, Microbiology and Immunology, 69(3), 133-147, 2024-12-15, https://doi.org/10.1111/1348-0421.13193 |
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言語 |
en |
| bibliographic_information |
en : Microbiology and Immunology
巻 69,
号 3,
p. 133-147,
発行日 2024-12-15
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| 出版者 |
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出版者 |
Wiley |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
0385-5600 |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1348-0421 |
| item_10001_relation_14 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1111/1348-0421.13193 |
| 権利 |
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権利情報 |
© 2024 The Author(s) |
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言語 |
en |
| 出版タイプ |
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出版タイプ |
VoR |
Fulltext (1.7 MB)
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