Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli

• Published in: Cell chemical biology Vol. 27; no. 6; pp. 698 - 707.e7
• Main 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 18.06.2020
• Subjects: Animals; antibiotic tolerance; Arabidopsis - metabolism; E. coli; Escherichia coli - cytology; Escherichia coli - metabolism; Feces - microbiology; host-bacteria interactions; Humans; IL-6; indole; Indoles - chemistry; Indoles - metabolism; innate immunity; Mice; Mice, Inbred C57BL; Molecular Structure; Oxidative Stress; persister cell; Signal Transduction; signaling; stress response; Up-Regulation; stress response; indole; signaling; innate immunity; persister cell; antibiotic tolerance; E. coli; IL-6; host-bacteria interactions
• ISSN: 2451-9456; 2451-9456; 2451-9448
• DOI: 10.1016/j.chembiol.2020.03.003

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. [Display omitted] •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 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.