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.
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Date of publication: 2 April 2020; Cell Chemical Biology
Author information: Chung Sub Kim (1,2); Jhe-Hao (1,2); Brenden Barco (3); Hyun Bong Park (1,2); Alexandra Gatsios (1,2); Ashiti Damania (3); Rurun Wang (4); Thomas P. Wyche (4); Grazia Piizzi (4); Nicole K. Clay (3); & Jason M. Crawford (1,2,5)
(1) Department of Chemistry, Yale University, New Haven, CT 06520, USA
(2) Chemical Biology Institute, Yale University, West Haven, CT 06516, USA
(3) Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA
(4) Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA
(5) Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA