Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

Chung Sub Kim, Alexandra Gatsios, Santiago Cuesta, Yick Chong Lam, Zheng Wei, Haiwei Chen, Regan M. Russell, Emilee E. Shine, Rurun Wang, Thomas P. Wyche, Grazia Piizzi, Richard A. Flavell, Noah W. Palm, Vanessa Sperandio, Jason M. Crawford

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Escherichia coli is a common inhabitant of the human microbiota and a beacon model organism in biology. However, an understanding of its signaling systems that regulate population-level phenotypes known as quorum sensing remain incomplete. Here, we define the structure and biosynthesis of autoinducer-3 (AI-3), a metabolite of previously unknown structure involved in the pathogenesis of enterohemorrhagic E. coli (EHEC). We demonstrate that novel AI-3 analogs are derived from threonine dehydrogenase (Tdh) products and "abortive" tRNA synthetase reactions, and they are distributed across a variety of Gram-negative and Gram-positive bacterial pathogens. In addition to regulating virulence genes in EHEC, we show that the metabolites exert diverse immunological effects on primary human tissues. The discovery of AI-3 metabolites and their biochemical origins now provides a molecular foundation for investigating the diverse biological roles of these elusive yet widely distributed bacterial signaling molecules.

Original languageEnglish (US)
Pages (from-to)197-206
Number of pages10
JournalACS Central Science
Volume6
Issue number2
DOIs
StatePublished - Feb 26 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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