Abstract
Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.
Highlights
Porphyromonas gingivalis is a gram-negative bacterium strongly associated with chronic periodontitis [1,2,3]
Based on the well-known fact that viral entry is involved in receptor-mediated endocytosis [25], we propose that Alop1 may block the entry of P. gingivalis and its outer membrane vesicles (OMV) into primary oral keratinocytes
Our results demonstrated that both compounds inhibit P. gingivalis invasion
Summary
Porphyromonas gingivalis is a gram-negative bacterium strongly associated with chronic periodontitis [1,2,3]. The pathogenicity of P. gingivalis has been extensively characterized, including its abilities to colonize the surfaces of oral tissues, interact with other oral bacteria, induce a destructive immune response, and invade host cells [5,6,7,8]. All of these virulence features have been attractive therapeutic targets for preventing P. gingivalis infection. P. gingivalis invasion is believed to protect the bacteria against environmental challenges, including innate immune surveillance systems and antibiotic treatment [15], which likely plays a pivotal role in chronic
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