| Item type |
文献 / Documents(1) |
| 公開日 |
2023-03-23 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3390/ijms232314697 |
|
|
言語 |
ja |
|
|
関連名称 |
10.3390/ijms232314697 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds |
|
言語 |
en |
| 著者 |
クマガイ, ケイゴ
サカイ, ショウタ
上野, 雅晴
カタオカ, ミチヨ
コバヤシ, シュウ
ハナダ, ケンタロウ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
infectious disease |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Chlamydia trachomatis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
bacterial metabolism |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
antibiotics |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
ceramide |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
sphingolipid |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
inhibitor |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
stereoselectivity |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
CERT |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
sphingomyelin synthase |
| 書誌情報 |
en : International Journal of Molecular Sciences
巻 23,
号 23,
p. 14697,
発行日 2022-11-24
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
14220067 |
| 出版者 |
|
|
出版者 |
MDPI |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| EID |
|
|
識別子 |
393338 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
ijms_23_23_14697.pdf (4.31 MB)
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