Streptococcus gordoniiprograms epithelial cells to resist ZEB2 induction byPorphyromonas gingivalis

Abstract

The polymicrobial microbiome of the oral cavity is a direct precursor of periodontal diseases, and changes in microhabitat or shifts in microbial composition may also be linked to oral squamous cell carcinoma. Dysbiotic oral epithelial responses provoked by individual organisms, and which underlie these diseases, are widely studied. However, organisms may influence community partner species through manipulation of epithelial cell responses, an aspect of the host microbiome interaction that is poorly understood. We report here thatPorphyromonas gingivalis, a keystone periodontal pathogen, can up-regulate expression of ZEB2, a transcription factor which controls epithelial–mesenchymal transition and inflammatory responses. ZEB2 regulation byP. gingivaliswas mediated through pathways involving β-catenin and FOXO1. Among the community partners ofP. gingivalis,Streptococcus gordoniiwas capable of antagonizing ZEB2 expression. Mechanistically,S. gordoniisuppressed FOXO1 by activating the TAK1-NLK negative regulatory pathway, even in the presence ofP. gingivalis. Collectively, these results establishS. gordoniias homeostatic commensal, capable of mitigating the activity of a more pathogenic organism through modulation of host signaling.