Evidence map›Paper›PMID 41044363›Full record

ArticleNature microbiology2025

Discovery and artificial intelligence-guided mechanistic elucidation of a narrow-spectrum antibiotic.

Denise B Catacutan, Vian Tran, Autumn Arnold, Jeremie Alexander, Gabriele Corso, Yeganeh Yousefi, Megan M Tu, Stewart McLellan, Dominique Tertigas, Kimberly Corneil and 6 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Artificial Intelligence-Guided Phenotypic Drug Repurposing Against Streptococcus pneumoniae.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Denise B CatacutanDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0009-0003-0146-5344
Vian TranDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Autumn ArnoldDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Jeremie AlexanderDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Gabriele CorsoComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yeganeh YousefiDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Megan M TuDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0001-7405-0500
Stewart McLellanDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Dominique TertigasDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0009-0008-3245-1355
Kimberly CorneilDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Jakob MagolanDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Michael G SuretteDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0003-0086-4995
Eric D BrownDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0002-7624-8112
Brian K CoombesDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0001-9883-1010
Regina BarzilayComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jonathan M StokesDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. stokesjm@mcmaster.ca.ORCID http://orcid.org/0009-0001-8378-2380

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current clinical antibiotics are largely broad-spectrum agents that can alter the gut microbiome and promote colonization by Enterobacteriaceae, which are often drug resistant. This includes adherent-invasive Escherichia coli (AIEC), particularly in patients with inflammatory bowel disease, in which dysbiosis creates a niche for this pathogen to colonize. There is an urgent and unmet need for novel narrow-spectrum and microbiome-sparing antibiotics. Here we screened 10,747 bioactive small molecules for antibacterial activity against AIEC and discovered enterololin, an antibacterial compound with targeted activity against Enterobacteriaceae species. Enterololin could overcome intrinsic and acquired resistance mechanisms in clinical isolates when combined with a subinhibitory concentration of SPR741, a polymyxin B analogue used here to increase outer membrane permeability in Gram-negative bacteria. Molecular substructure- and deep learning-guided mechanism-of-action investigations revealed that enterololin perturbs lipoprotein trafficking through a mechanism involving the LolCDE complex, laboratory-evolved resistant mutants predominantly mapped to lolC and lolE, with an in vitro frequency of resistance of ~10

Indexed as

Anti-Bacterial AgentsArtificial IntelligenceDrug DiscoveryAnimalsDrug Resistance, BacterialEnterobacteriaceaeEscherichia coliEscherichia coli InfectionsGastrointestinal MicrobiomeHumansMiceMicrobial Sensitivity TestsAnti-Bacterial Agents

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.