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结核分枝杆菌 Rv1980c 蛋白中与人细胞感染相关的肽:对新型合成亚单位疫苗候选物的深入了解。

Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates.

机构信息

Fundación Instituto de Inmunología de Colombia (FIDIC), Cra. 50 No. 26-20, Bogotá, Colombia.

School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.

出版信息

Biol Chem. 2010 Feb-Mar;391(2-3):207-217. doi: 10.1515/bc.2010.019.

Abstract

Mycobacterium tuberculosis infection continues to be a major cause of morbidity and mortality throughout the world. The vast complexity of the intracellular pathogen M. tuberculosis and the diverse mechanisms by which it can invade host cells highlight the importance of developing a fully protective vaccine. Our vaccine development strategy consists of including fragments from multiple mycobacterial proteins involved in cell invasion. The aim of this study was to identify high activity binding peptides (HABPs) in the immunogenic protein Rv1980c from M. tuberculosis H37Rv with the ability to inhibit mycobacterial invasion into U937 monocyte-derived macrophages and A549 cells. The presence and transcription of the Rv1980c gene was assessed in members belonging to the M. tuberculosis complex and other nontuberculous mycobacteria by PCR and RT-PCR, respectively. Cell surface localization was confirmed by immuno-electron microscopy. Three peptides binding with high activity to U937 cells and one to A549 cells were identified. HABPs 31100, 31101, and 31107 inhibited invasion of M. tuberculosis into A549 and U937 cells and therefore could be promising candidates for the design of a subunit-based antituberculous vaccine.

摘要

结核分枝杆菌感染仍是全球范围内发病率和死亡率的主要原因。结核分枝杆菌这种细胞内病原体的复杂性以及它能够侵入宿主细胞的多种机制突出表明,开发一种完全保护性疫苗至关重要。我们的疫苗开发策略包括包含参与细胞入侵的多个分枝杆菌蛋白的片段。本研究的目的是鉴定结核分枝杆菌 H37Rv 中免疫原性蛋白 Rv1980c 中的高活性结合肽(HABP),这些肽具有抑制分枝杆菌侵入 U937 单核细胞衍生巨噬细胞和 A549 细胞的能力。通过 PCR 和 RT-PCR 分别评估了结核分枝杆菌复合体成员和其他非结核分枝杆菌中 Rv1980c 基因的存在和转录。通过免疫电子显微镜证实了细胞表面定位。鉴定出三个与 U937 细胞结合具有高活性的肽和一个与 A549 细胞结合具有高活性的肽。HABP 31100、31101 和 31107 抑制了结核分枝杆菌进入 A549 和 U937 细胞的侵袭,因此可能是设计基于亚单位的抗结核疫苗的有前途的候选物。

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