Engineered phage-based therapeutic materials inhibit Chlamydia trachomatis intracellular infection.
Engineered phage-based therapeutic materials inhibit Chlamydia trachomatis intracellular infection.
复制标题
DOI：
10.1016/j.biomaterials.2012.03.054
复制
发表时间：
2012-07
期刊：
影响因子：
14
通讯作者：
Dean, Deborah
中科院分区：
文献类型：
--
作者：
Bhattarai, Shanta Raj;Yoo, So Young;Lee, Seung-Wuk;Dean, Deborah
开发有效对抗性传播病原体如沙眼衣原体（Ct）和HIV-1的材料在材料选择和改善所需粘膜部位的生物膜和细胞渗透性方面都具有挑战性。在这里，我们设计的原核细菌病毒（M13噬菌体）携带两个功能肽，整合素结合肽（RGD）和一段多态性膜蛋白D（PmpD）从Ct，作为噬菌体为基础的材料，可以改善Ct感染。Ct是一种全球流行的人类病原体，目前尚无有效的疫苗或杀微生物剂。我们表明，工程噬菌体稳定表达的RGD基序和Ct肽和交通胞内和进入管腔的包涵体中的生物体驻留在宿主细胞内。与单独的Ct感染相比，工程化噬菌体能够显著降低HeLa和原代宫颈内细胞中的Ct感染。针对PmpD产生的多克隆抗体并在感染前与构建体共孵育不改变感染过程，表明PmpD是观察到的Ct感染减少的原因。我们的研究结果表明，以噬菌体为基础的设计方法，载体交付，克服粘膜细胞屏障可能是有效的，在防止Ct和其他性传播病原体。
Developing materials that are effective against sexually transmitted pathogens such as Chlamydia trachomatis (Ct) and HIV-1 is challenging both in terms of material selection and improving bio-membrane and cellular permeability at desired mucosal sites. Here, we engineered the prokaryotic bacterial virus (M13 phage) carrying two functional peptides, integrin binding peptide (RGD) and a segment of the polymorphic membrane protein D (PmpD) from Ct, as a phage-based material that can ameliorate Ct infection. Ct is a globally prevalent human pathogen for which there are no effective vaccines or microbicides. We show that engineered phage stably express both RGD motifs and Ct peptides and traffic intracellularly and into the lumen of the inclusion in which the organism resides within the host cell. Engineered phage were able to significantly reduce Ct infection in both HeLa and primary endocervical cells compared with Ct infection alone. Polyclonal antibodies raised against PmpD and co-incubated with constructs prior to infection did not alter the course of infection, indicating that PmpD is responsible for the observed decrease in Ct infection. Our results suggest that phage-based design approaches to vector delivery that overcome mucosal cellular barriers may be effective in preventing Ct and other sexually transmitted pathogens.
登录
查看更多内容
影响因子：
3.7
作者：
Kiselev, Andrey O.;Skinner, Megan C.;Lampe, Mary F.
通讯作者：
Lampe, Mary F.
影响因子：
3.3
作者：
Bhengraj, Apurb Rashmi;Vardhan, Harsh;Mittal, Aruna
通讯作者：
Mittal, Aruna
影响因子：
3.9
作者：
Chung, Woo-Jae;Merzlyak, Anna;Lee, Seung-Wuk
通讯作者：
Lee, Seung-Wuk
影响因子：
64.8
作者：
Chung, Woo-Jae;Oh, Jin-Woo;Lee, Seung-Wuk
通讯作者：
Lee, Seung-Wuk
影响因子：
5.1
作者：
Erbacher, P;Remy, JS;Behr, JP
通讯作者：
Behr, JP