De Novo Designed α-Sheet Peptides Inhibit Functional Amyloid Formation of Streptococcus mutans Biofilms.
De Novo Designed α-Sheet Peptides Inhibit Functional Amyloid Formation of Streptococcus mutans Biofilms.
复制标题
DOI：
10.1016/j.jmb.2018.07.005
复制
发表时间：
2018-10-12
影响因子：
5.6
通讯作者：
Daggett V
中科院分区：
文献类型：
--
作者：
Paranjapye N;Daggett V
变异链球菌是一种在口腔微生物群中占优势的细菌。S.变异蛋白结合到牙齿表面，代谢糖并产生酸，导致蛀牙的形成。S.变异菌也能引起感染性心内膜炎。最近的证据表明S.变异菌生物膜含有淀粉样原纤维。淀粉样蛋白是不溶性纤维状蛋白聚集体，细菌利用功能性淀粉样蛋白来提高其生物膜的坚固性。而细菌如大肠杆菌中的功能性淀粉样蛋白。coli和革兰氏阳性菌S.金黄色葡萄球菌（S. aureus）是近年来研究的热点，但对S.变异淀粉样蛋白形成。我们实验室先前对上述细菌和其他哺乳动物淀粉样蛋白系统的淀粉样蛋白形成蛋白和肽的研究结果表明，淀粉样蛋白的形成是通过一种采用独特二级结构- α-折叠的中间体进行的。具有交替的L-和D-氨基酸的从头设计的肽也采用α-折叠二级结构，并在淀粉样蛋白形成期间通过与可溶性寡聚物结合来抑制淀粉样蛋白形成。α-折叠肽对纤维化的抑制表明在淀粉样蛋白形成过程中存在α-折叠。目的：探讨淀粉样蛋白在S.将α-折叠肽与表没食子儿茶素没食子酸酯（EGCG）比较其抑制S.变异人在生物膜平板试验和羟基磷灰石表面上均在S.以及人类唾液中的细菌。观察到的抑制表明，α折叠介导的机制可能在功能性淀粉样蛋白形成期间起作用。
Streptococcus mutans is a bacterial species that predominates in the oral microbiome. S. mutans binds to the tooth surface, metabolizes sugars and produces acid, leading to cavity formation. S. mutans can also cause infectious endocarditis. Recent evidence suggests that S. mutans biofilms contain amyloid fibrils. Amyloids are insoluble fibrillar protein aggregates, and bacteria use functional amyloids to improve robustness of their biofilms. While the functional amyloids in bacteria such as E. coli and S. aureus have been heavily investigated, little is known about the mechanism of S. mutans amyloid formation. Previous results from our lab with the amyloidogenic proteins and peptides from the aforementioned bacteria and other mammalian amyloid systems suggest that amyloid formation progresses via an intermediate that adopts a unique secondary structure – α-sheet. De novo designed peptides with alternating L- and D- amino acid also adopt an α–sheet secondary structure and inhibit amyloid formation by binding to soluble oligomeric species during amyloidogenesis. Inhibition of fibrillization by α-sheet peptides suggests the presence of α-sheet during amyloid formation. To investigate the mechanism of functional amyloid formation in S. mutans, α-sheet peptides were compared to Epigallocatechin gallate (EGCG) for their ability to inhibit fibril formation in S. mutans. Inhibition was demonstrated in a biofilm plate assay and on hydroxyapatite surfaces both in S. mutans alone and in bacteria from human saliva. The observed inhibition suggests that an α-sheet mediated mechanism may be operative during functional amyloid formation.
登录
查看更多内容
影响因子：
6.6
作者：
Chen F;Wang D
通讯作者：
Wang D
DOI：
10.3109/10731199909117706
发表时间：
1999-01-01
影响因子：
--
作者：
Oktar, FN;Kesenci, K;Piskin, E
通讯作者：
Piskin, E
影响因子：
5.6
作者：
Kayed, R;Bernhagen, J;Kapurniotu, A
通讯作者：
Kapurniotu, A
影响因子：
2.8
作者：
Besingi, Richard N.;Wenderska, Iwona B.;Brady, L. Jeannine
通讯作者：
Brady, L. Jeannine
DOI：
10.1073/pnas.0910723107
发表时间：
2010-04-27
影响因子：
11.1
作者：
Bieschke, Jan;Russ, Jenny;Wanker, Erich E.
通讯作者：
Wanker, Erich E.