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

TY - JOUR

T1 - Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

AU - Kim, Chung Sub

AU - Gatsios, Alexandra

AU - Cuesta, Santiago

AU - Lam, Yick Chong

AU - Wei, Zheng

AU - Chen, Haiwei

AU - Russell, Regan M.

AU - Shine, Emilee E.

AU - Wang, Rurun

AU - Wyche, Thomas P.

AU - Piizzi, Grazia

AU - Flavell, Richard A.

AU - Palm, Noah W.

AU - Sperandio, Vanessa

AU - Crawford, Jason M.

N1 - Publisher Copyright: Copyright © 2020 American Chemical Society.

PY - 2020/2/26

Y1 - 2020/2/26

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85080835557

UR - https://www.scopus.com/pages/publications/85080835557#tab=citedBy

U2 - 10.1021/acscentsci.9b01076

DO - 10.1021/acscentsci.9b01076

M3 - Article

SN - 2374-7943

VL - 6

SP - 197

EP - 206

JO - ACS Central Science

JF - ACS Central Science

IS - 2

ER -