MIT AI reveals how antibiotic targets Crohn’s bacteria

MIT and McMaster researchers used AI to map how a narrow-spectrum antibiotic attacks harmful gut bacteria. Enterololin targets E. coli linked to Crohn’s flares while preserving most of the microbiome, providing a precise alternative to broad-spectrum antibiotics.

AI accelerated the process of identifying the drug’s mechanism of action, reducing a task that usually takes years to just months.

The team used DiffDock, a generative AI tool developed at MIT, to predict how enterololin binds to a protein complex called LolCDE in E. coli. Laboratory experiments, including mutant evolution, RNA sequencing, and CRISPR knockdowns, confirmed the AI predictions.

The method demonstrates how AI can provide mechanistic insights, guide experiments, and speed up early-stage antibiotic development.

Enterololin improved recovery and preserved the microbiome in mouse models compared with conventional treatments. Researchers aim to develop derivatives against resistant pathogens like Klebsiella pneumoniae, with early work underway at spinout company Stoked Bio.

The study highlights broader implications for precision antibiotics, which could treat infections without disrupting beneficial microbes. AI-driven mechanism mapping could speed up drug discovery, cut costs, and help tackle antimicrobial resistance.

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