Porphyromonas gingivalis, a keystone species in the development of periodontal disease, is a suspected cause of Alzheimer's disease. This bacterium is reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize gingipain susceptibility, we performed enrichment analyses of arginine and lysine proportion proteome-wide. Proteins in the SRP-dependent cotranslational protein targeting to membrane pathway were enriched for these residues and previously associated with periodontal and Alzheimer's disease. These ribosomal genes are up-regulated in prefrontal cortex samples with detected P. gingivalis sequences. Other differentially expressed genes have been previously associated with dementia (ITM2B, MAPT, ZNF267, and DHX37). For an anatomical perspective, we characterized the expression of the P. gingivalis associated genes in the mouse and human brain. This analysis highlighted the hypothalamus, cholinergic neurons, and the basal forebrain. Our results suggest markers of neural P. gingivalis infection and link the gingipain and cholinergic hypotheses of Alzheimer's disease.

中文翻译：

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对牙龈蛋白酶的敏感性和对牙龈卟啉单胞菌的转录组反应突出了核糖体，下丘脑和胆碱能神经元。

牙龈卟啉单胞菌（Porphyromonas gingivalis）是牙周病发展中的关键物种，被怀疑是阿尔茨海默氏病的病因。这种细菌依赖于姜黄素蛋白酶，后者在精氨酸和赖氨酸残基之后裂解宿主蛋白。为了表征姜黄素敏感性，我们在整个蛋白质组中进行了精氨酸和赖氨酸比例的富集分析。靶向膜途径的SRP依赖性共翻译蛋白中的蛋白质富含这些残基，以前与牙周病和阿尔茨海默氏病有关。这些核糖体基因在前额叶皮层样本中具有检测到的牙龈卟啉单胞菌序列上调。其他差异表达的基因先前已与痴呆症相关联（ITM2B，MAPT，ZNF267和DHX37）。从解剖学角度，我们对P的表达进行了表征。小鼠和人脑中的牙龈相关基因。该分析突出了下丘脑，胆碱能神经元和基底前脑。我们的研究结果提示了神经牙龈卟啉单胞菌感染的标志物，并将其与阿格海默氏病的姜黄素和胆碱能假说联系起来。