Giannakou Lydia-Eirini, Giannopoulos Athanasios-Stefanos, Hatzoglou Chrissi, Gourgoulianis Konstantinos I, Rouka Erasmia, Zarogiannis Sotirios G
Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.
Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.
Pathophysiology. 2021 Jan 2;28(1):20-33. doi: 10.3390/pathophysiology28010003.
(), () and () are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the , and pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.
肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌是导致人类呼吸道疾病的三种最常见革兰氏阴性菌。在本研究中,我们旨在通过功能富集分析(FEA)确定与上述细菌相互作用的人类基因网络,以阐明诱导致病性的全貌。人类病原体相互作用数据库(HPIDB 3.0)用于识别与这三种病原体相互作用的人类蛋白质。通过ToppGene Suite的ToppFun工具和GeneCodis数据库进行FEA,以识别生物过程(BP)、细胞成分(CC)和疾病的富集基因本体(GO)。总共发现11种人类蛋白质与细菌病原体相互作用。BP GOs的FEA揭示了与凋亡途径中线粒体膜通透性的关联。CC GOs的FEA揭示了与粘着斑、细胞连接和外泌体的关联。疾病和途径中最显著富集的注释分别是肺腺癌和细胞周期。我们的结果表明,肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌病原体可能通过靶向上皮细胞连接以及随后细胞粘附和凋亡途径的失调,与肺腺癌的发病机制和/或进展相关。这些假设应通过实验进行验证。