Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis

PLoS One. 2016 Feb 19;11(2):e0149618. doi: 10.1371/journal.pone.0149618. eCollection 2016.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cells, Cultured
  • Dynamins / antagonists & inhibitors
  • Endocytosis / drug effects
  • Humans
  • Hydrazones / pharmacology*
  • Keratinocytes / drug effects
  • Keratinocytes / microbiology
  • Microtubules / microbiology
  • Mouth Mucosa / microbiology*
  • Piperidines / pharmacology*
  • Porphyromonas gingivalis / drug effects*
  • Porphyromonas gingivalis / physiology
  • Quinolizidines

Substances

  • Hydrazones
  • N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
  • Piperidines
  • Quinolizidines
  • aloperine
  • Dynamins