AUTHOR=Patel Sejal , Howard Derek , Chowdhury Nityananda , Derieux Casey , Wellslager Bridgette , Yilmaz Özlem , French Leon 

TITLE=Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.646259

DOI=10.3389/fimmu.2021.646259

ISSN=1664-3224

ABSTRACT=<p><italic>Porphyromonas gingivalis</italic>, a bacterium associated with 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. Genes differentially expressed in brain samples with detected <italic>P. gingivalis</italic> reads were also examined. Genes from these analyses were tested for functional enrichment and specific neuroanatomical expression patterns. 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 <italic>P. gingivalis</italic> sequences. Other differentially expressed genes have been previously associated with dementia (<italic>ITM2B</italic>, <italic>MAPT</italic>, <italic>ZNF267</italic>, and <italic>DHX37</italic>). For an anatomical perspective, we characterized the expression of the <italic>P. gingivalis</italic> 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 <italic>P. gingivalis</italic> infection and link the cholinergic and gingipain hypotheses of Alzheimer’s disease.</p>