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4h ago

AI Reveals How Enterololin Works, Advancing a Precision Antibiotic for IBD

A generative docking model identified LolCDE as the target, enabling a faster, lower-cost path to mechanism validation.

By using AI to sift through more than 10,000 molecules, researchers found enterololin (inset), a compound that blocks a key pathway in harmful gut bacteria and, in mice with IBD, eased infection without disturbing the rest of the microbiome.

Overview

  • Researchers at MIT and McMaster report enterololin in Nature Microbiology as a narrow-spectrum agent that suppresses Enterobacteriaceae linked to Crohn’s disease flare-ups.
  • DiffDock predicted binding to the LolCDE lipoprotein-transport complex in minutes, providing a concrete lead that directed subsequent lab tests.
  • Mechanism validation came from evolved E. coli resistance mutations mapping to lolCDE, RNA sequencing signatures, and CRISPR knockdowns consistent with lipoprotein transport disruption.
  • In mouse models of Crohn’s-like inflammation, enterololin targeted E. coli, accelerated recovery, and preserved the gut microbiome compared with vancomycin.
  • Stoked Bio has licensed the compound for optimization with clinical trials projected within the next few years, and the team released sequencing data and DiffDock-L code publicly.