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Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas 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 that Porphyromonas gingivalis, a keystone periodontal pathogen, can up-regulate expression of ZEB2, a transcription factor which controls epithelial-mesenchymal transition and inflammatory responses. ZEB2 regulation by P. gingivalis was mediated through pathways involving ?-catenin and FOXO1. Among the community partners of P. gingivalis, Streptococcus gordonii was capable of antagonizing ZEB2 expression. Mechanistically, S. gordonii suppressed FOXO1 by activating the TAK1-NLK negative regulatory pathway, even in the presence of P. gingivalis Collectively, these results establish S. gordonii as homeostatic commensal, capable of mitigating the activity of a more pathogenic organism through modulation of host signaling.

SUBMITTER: Ohshima J 

PROVIDER: S-EPMC6486779 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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<i>Streptococcus gordonii</i> programs epithelial cells to resist ZEB2 induction by <i>Porphyromonas gingivalis</i>.

Ohshima Jun J   Wang Qian Q   Fitzsimonds Zackary R ZR   Miller Daniel P DP   Sztukowska Maryta N MN   Jung Young-Jung YJ   Hayashi Mikako M   Whiteley Marvin M   Lamont Richard J RJ  

Proceedings of the National Academy of Sciences of the United States of America 20190410 17


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 po  ...[more]

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