Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli. Issue 6 (18th June 2020)

• Record Type: Journal Article
• Authors: Kim, Chung Sub; Li, Jhe-Hao; Barco, Brenden; Park, Hyun Bong; Gatsios, Alexandra; Damania, Ashiti; Wang, Rurun; Wyche, Thomas P.; Piizzi, Grazia; Clay, Nicole K.; Crawford, Jason M.
• Is Part Of: Cell chemical biology. Volume 27:Issue 6(2020)
• Page Start: 698
• Page End: 707.e7
• Publication Date: 2020-06-18
• Subjects: stress response -- indole -- signaling -- E. coli -- IL-6 -- host-bacteria interactions -- persister cell -- antibiotic tolerance -- innate immunity; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2020.03.003
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Escherichia coli broadly colonize the intestinal tract of humans and produce a variety of small molecule signals. However, many of these small molecules remain unknown. Here, we describe a family of widely distributed bacterial metabolites termed the "indolokines." In E. coli, the indolokines are upregulated in response to a redox stressor via aspC and tyrB transaminases. Although indolokine 1 represents a previously unreported metabolite, four of the indolokines (2–5 ) were previously shown to be derived from indole-3-carbonyl nitrile (ICN) in the plant pathogen defense response. We show that the indolokines are produced in a convergent evolutionary manner relative to plants, enhance E. coli persister cell formation, outperform ICN protection in an Arabidopsis thaliana-Pseudomonas syringae infection model, trigger a hallmark plant innate immune response, and activate distinct immunological responses in primary human tissues. Our molecular studies link a family of cellular stress-induced metabolites to defensive responses across bacteria, plants, and humans. Graphical Abstract: Highlights: Cellular stress-induced indole metabolites termed indolokines in diverse bacteria Indolokines were identified in fecal samples and enhanced E. coli persister formation Indolokines outperformed plant defense metabolites in Arabidopsis-Pseudomonas model Indolokines activated human aryl hydrocarbon receptor and induced IL-6 secretion Abstract : Kim, Li, et al. describe the characterization of cellular stress-induced, bacterial indole-functionalized metabolites termed "indolokines." The indolokines are found in diverse bacteria, enhance persister formation in E. coli, and activate innate immune responses in both plant and human tissues.