Ke, Xiaobo and Porter, Jeffrey Identification of Bacterial Metabolites that Modulate Endoplasmic Reticulum Stress.

Abstract

Many inflammatory diseases are associated with dysbiosis of the human microbiota. The mechanisms by which these microbes influence diseases remain elusive. Since endoplasmic reticulum (ER) stress induced inflammation has been indicated in many diseases, gut microbes potentially influence inflammatory diseases through ER stress modulation. Using a colorectal adenocarcinoma cell line carrying GFP fusion reporter for XBP1, a key ER stress regulator, we performed a high content imaging screen to identify bacterial extracts and purified microbiome compounds that could modulate ER stress response. We did not identify ER stress modulation activity from extracts prepared from 30 bacterial species cultured across multiple growth media conditions. However, when a collection of microbiome metabolites were screened, several bacterial encoded natural products demonstrated ER stress response modulation activities. For instance, a Clostridium derived dipeptide aldehyde activates ER stress response, potentially through inhibition of proteases and proteosome. In contrast, soraphen A, a bacterial polyketide could inhibit ER stress response induced by tunicamycin. These findings indicates that commensal microbes encodes the potential to modulate ER stress response,

Item Type:	Article
Date Deposited:	18 Jul 2020 00:45
Last Modified:	18 Jul 2020 00:45
URI:	https://oak.novartis.com/id/eprint/41159