Evidence map›Paper›PMID 39333560›Full record

ArticleNature communications2024

Computer-aided drug design to generate a unique antibiotic family.

Christopher J Barden, Fan Wu, J Pedro Fernandez-Murray, Erhu Lu, Shengguo Sun, Marcia M Taylor, Annette L Rushton, Jason Williams, Mahtab Tavasoli, Autumn Meek and 8 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Virtual screening and experimental validation of a METTL3-targeting peptide withJournal of enzyme inhibition and medicinal chemistry · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Synergistic effects ofFrontiers in antibiotics · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Christopher J BardenKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Fan WuKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
J Pedro Fernandez-MurrayDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.ORCID 0000-0002-9921-5487
Erhu LuKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Shengguo SunKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Marcia M TaylorKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Annette L RushtonDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Jason WilliamsDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Mahtab TavasoliDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.ORCID 0000-0001-7962-3566
Autumn MeekKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-6902-4620
Alla Siva ReddyKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Lisa M DoyleKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Irina SagamanovaKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Kovilpitchai SivamuthuramanKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Robert T M BoudreauDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.
David M ByersDepartment of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada.
Donald F WeaverKrembil Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.
Christopher R McMasterDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada. Christopher.mcmaster@dal.ca.ORCID 0000-0003-0822-5776

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) SOP-159230
6 · The paper itself

Abstract

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 μg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.

Indexed as

Anti-Bacterial AgentsComputer-Aided DesignDrug DesignMicrobial Sensitivity TestsAnimalsColistinDiabetic FootDrug Resistance, Multiple, BacterialDrug SynergismGram-Negative BacteriaGram-Positive BacteriaHumansMiceAnti-Bacterial AgentsColistin

Identifiers

PMID39333560
PMCPMC11436758

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.