Kabir Ali Rejwan, Chaudhary Anis Ahmad, Aladwani Malak O, Podder Soumita
Computational and System Biology Lab, Department of Microbiology, Raiganj University, Raiganj, West Bengal, India.
Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Front Genet. 2023 Oct 12;14:1245445. doi: 10.3389/fgene.2023.1245445. eCollection 2023.
The objective of this study is to investigate the interaction between and human proteins during oral candidiasis, with the aim of identifying pathways through which the pathogen subverts host cells. A comprehensive list of interactions between human proteins and was obtained from the Human Protein Interaction Database using specific screening criteria. Then, the genes that exhibit differential expression during oral candidiasis in were mapped with the list of human- interactions to identify the corresponding host proteins. The identified host proteins were further compared with proteins specific to the tongue, resulting in a final list of 99 host proteins implicated in oral candidiasis. The interactions between host proteins and proteins were analyzed using the STRING database, enabling the construction of protein-protein interaction networks. Similarly, the gene regulatory network of proteins was reconstructed using data from the PathoYeastract and STRING databases. Core module proteins within the targeted host protein-protein interaction network were identified using ModuLand, a Cytoscape plugin. The expression levels of the core module proteins under diseased conditions were assessed using data from the GSE169278 dataset. To gain insights into the functional characteristics of both host and pathogen proteins, ontology analysis was conducted using Enrichr and YeastEnrichr, respectively. The analysis revealed that three proteins, HHT21, CYP5, and KAR2, interact with three core host proteins, namely, ING4 (in the DNMT1 module), SGTA, and TOR1A. These interactions potentially impair the immediate immune response of the host against the pathogen. Additionally, differential expression analysis of fungal proteins and their transcription factors in -infected oral cell lines indicated that Rob1p, Tye7p, and Ume6p could be considered candidate transcription factors involved in instigating the pathogenesis of oral candidiasis during host infection. Our study provides a molecular map of the host-pathogen interaction during oral candidiasis, along with potential targets for designing regimens to overcome oral candidiasis, particularly in immunocompromised individuals.
本研究的目的是调查[病原体名称]与人类蛋白质在口腔念珠菌病期间的相互作用,以确定病原体颠覆宿主细胞的途径。使用特定筛选标准从人类蛋白质相互作用数据库中获得了人类蛋白质与[病原体名称]之间相互作用的综合列表。然后,将在[病原体名称]引起的口腔念珠菌病期间表现出差异表达的基因与人类 - [病原体名称]相互作用列表进行比对,以鉴定相应的宿主蛋白质。将鉴定出的宿主蛋白质与舌特异性蛋白质进一步比较,得出了99种与口腔念珠菌病相关的宿主蛋白质的最终列表。使用STRING数据库分析宿主蛋白质与[病原体名称]蛋白质之间的相互作用,从而构建蛋白质 - 蛋白质相互作用网络。同样,使用来自PathoYeastract和STRING数据库的数据重建[病原体名称]蛋白质的基因调控网络。使用Cytoscape插件ModuLand鉴定靶向宿主蛋白质 - 蛋白质相互作用网络中的核心模块蛋白质。使用GSE169278数据集的数据评估患病条件下核心模块蛋白质的表达水平。为了深入了解宿主和病原体蛋白质的功能特征,分别使用Enrichr和YeastEnrichr进行本体分析。分析表明,三种[病原体名称]蛋白质HHT21、CYP5和KAR2与三种核心宿主蛋白质相互作用,即ING4(在DNMT1模块中)、SGTA和TOR1A。这些相互作用可能会损害宿主对病原体的即时免疫反应。此外,对感染[病原体名称]的口腔细胞系中真菌蛋白质及其转录因子的差异表达分析表明,Rob1p、Tye7p和Ume6p可被视为在宿主感染期间引发口腔念珠菌病发病机制的候选转录因子。我们的研究提供了口腔念珠菌病期间宿主 - 病原体相互作用的分子图谱,以及设计克服口腔念珠菌病方案的潜在靶点,特别是在免疫功能低下的个体中。