| RRC ID |
43010
|
| 著者 |
Neri P, Nagano SI, Yokoyama S, Dohi H, Kobayashi K, Miura T, Inazu T, Sugiyama T, Nishida Y, Mori H.
|
| タイトル |
Neutralizing activity of polyvalent Gb3, Gb2 and galacto-trehalose models against Shiga toxins.
|
| ジャーナル |
Microbiol Immunol
|
| Abstract |
Shiga toxin (Stx) is one of the most critical factors in the development of hemolytic uremic syndrome and other systemic complications following enterohemorrhagic Escherichia coli (EHEC) infection. Substances neutralizing Stx by interfering with toxin-receptor binding have been explored as therapeutic candidates for EHEC infection. In this study, we examined globotriaosyl (Gb3), galabiosyl (Gb2) and galacto-trehalose, each of which was synthetically conjugated with a polyacrylamide backbone, for Stxneutralizing activity. Galacto-trehalose was designed as a Gb2 mimicking, unnatural Stx-ligand that was expected to show tolerance to enzymatic degradation in vivo. Galacto-trehalose copolymer showed neutralizing activity against Stx-1 but not Stx-2 in a HeLa cell cytotoxicity assay. It was thought that galactotrehalose copolymer could be a lead compound for the treatment of Stx-mediated diseases, although it requires modification to show neutralizing activity to Stx-2. The Gb3 copolymer with high sugar unit density showed stronger neutralizing activity against Stx-2 than those with lower density. However, the density-dependency of the neutralizing activity was less obvious against Stx-1. Intravenous administration of the Gb3 copolymer prevented death in mice lethally infected with Stx-1- and Stx-2-producing E. coli O157:H7. Thus, we demonstrated that the artificial Gb3 copolymer could neutralize Stx-1 and the more clinically relevant Stx-2 in vitro and effectively inhibit Stx toxicity in vivo.
|
| 巻・号 |
51(6)
|
| ページ |
581-92
|
| 公開日 |
2007-1-1
|
| DOI |
10.1111/j.1348-0421.2007.tb03944.x
|
| PII |
JST.JSTAGE/mandi/51.581
|
| PMID |
17579269
|
| MeSH |
Animals
Carbohydrate Sequence
Escherichia coli Infections / drug therapy*
Escherichia coli Infections / microbiology
Escherichia coli O157 / metabolism*
Feces / microbiology
Female
Galactose / pharmacology*
HeLa Cells
Humans
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Shiga Toxin 1 / antagonists & inhibitors*
Shiga Toxin 1 / metabolism
Shiga Toxin 2 / antagonists & inhibitors*
Shiga Toxin 2 / metabolism
Specific Pathogen-Free Organisms
Trehalose / pharmacology*
|
| IF |
1.566
|
| 引用数 |
23
|
|
WOS 分野
|
IMMUNOLOGY
MICROBIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007) |
