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致病钩端螺旋体外膜蛋白的 hTLR2 相互作用肽。

hTLR2 interacting peptides of pathogenic leptospiral outer membrane proteins.

机构信息

Medical Microbiology Laboratory (MML), Department of Microbiology, Center for Excellence in Life Sciences, Bharathidasan University, Tiruchirappalli, 620024, India.

Medical Microbiology Laboratory (MML), Department of Microbiology, Center for Excellence in Life Sciences, Bharathidasan University, Tiruchirappalli, 620024, India.

出版信息

Microb Pathog. 2021 Jun;155:104895. doi: 10.1016/j.micpath.2021.104895. Epub 2021 Apr 17.

DOI:10.1016/j.micpath.2021.104895
PMID:33878396
Abstract

To adapt into the host system from moist environment Leptospira alter their gene expression by inducing differential expression of the genes encoding virulence factors. Knowledge about the molecular pathogenesis and virulent evolution remains limited to Leptospira. The pathogenic organism sense the environmental changes mainly through their outer membrane proteins that in-turn activates the signal transduction pathways to overcome the stress to adaptation into host system and to evade immunity. In this present study, we analyzed the expression profile of virulence associated OMPs regulated under various stress conditions like temperatures, iron deprivation, osmotic stress and low to high passages in single scale and characterized the selected proteins by MALDI-TOF MS/MS and their role in pathogenesis were predicted by implying in-silico analysis. To identify differential expression profile, the extracted OMPs were resolved through 2DE and compared the OMPs profile from various in-vivo like conditions in single scale and found 61 upregulated OMPs and three potentially virulent proteins were earmarked for their significance in pathogenesis. Further, the in-silico analysis revealed that differentially expressed protein has MHC-I T-cell, MHC-II T-cell and B-cell epitopes which showed an interaction between human TLR2 proteins confirmed by CABS docking and interaction network unveiled to understand the leptospiral virulent mechanism and host adaptation.

摘要

为了适应宿主系统的潮湿环境,钩端螺旋体通过诱导毒力因子基因的差异表达来改变其基因表达。关于分子发病机制和毒力进化的知识仍然仅限于钩端螺旋体。病原体主要通过其外膜蛋白感知环境变化,进而激活信号转导途径,以克服压力,适应宿主系统并逃避免疫。在本研究中,我们分析了在各种应激条件下(如温度、缺铁、渗透压应激和低至高传代)调节的与毒力相关的 OMPs 的表达谱,并通过 MALDI-TOF MS/MS 对选定的蛋白质进行了表征,并通过引入计算机分析预测了它们在发病机制中的作用。为了确定差异表达谱,通过 2DE 解析提取的 OMPs,并在单尺度上比较来自各种体内条件的 OMPs 谱,发现 61 个上调的 OMPs 和三个潜在的毒力蛋白因其在发病机制中的重要性而被标记。此外,计算机分析表明,差异表达蛋白具有 MHC-I T 细胞、MHC-II T 细胞和 B 细胞表位,这表明人类 TLR2 蛋白之间存在相互作用,通过 CABS 对接和相互作用网络进行了验证,以了解钩端螺旋体的毒力机制和宿主适应性。

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