Evidence map›Paper›PMID 38029756›Full record

ArticleCell chemical biology2024

Discovery of antibiotics that selectively kill metabolically dormant bacteria.

Erica J Zheng, Jacqueline A Valeri, Ian W Andrews, Aarti Krishnan, Parijat Bandyopadhyay, Melis N Anahtar, Alice Herneisen, Fabian Schulte, Brooke Linnehan, Felix Wong and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Artificial intelligence catalyzes antimicrobial peptide design.Synthetic and systems biotechnology · 2027
    Review
  2. Artificial Intelligence-Guided Phenotypic Drug Repurposing Against Streptococcus pneumoniae.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
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  7. Review
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  16. Review
  17. A rational approach to discovering new persister control agents.Antimicrobial agents and chemotherapy · 2025
    Article
  18. Article
  19. Article
  20. 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

14 authors.

Erica J ZhengProgram in Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Jacqueline A ValeriInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Ian W AndrewsInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Aarti KrishnanInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Parijat BandyopadhyayInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Melis N AnahtarInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Alice HerneisenWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
Fabian SchulteWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Brooke LinnehanWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Felix WongInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jonathan M StokesDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Lars D RennerLeibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, 01062 Dresden, Germany.
Sebastian LouridoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
James J CollinsInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA. Electronic address: jimjc@mit.edu.

Funding

MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Genetic, Metabolic and Regulatory Control of MIC and Relapse in M. tuberculosisR01AI146194 · NIAID · UNIVERSITY OF WASHINGTON · PI ALLAND, DAVID, SHERMAN, DAVID R · 2020 to 2024
$4.1M
Control of parasite invasion by a microneme protein complex conserved in ApicomplexansR01AI144369 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LOURIDO, SEBASTIAN · 2020 to 2024
$2.4M
Physical Biology and Deep Learning for Antibiotic Resistance and DiscoveryK25AI168451 · NIAID · BROAD INSTITUTE, INC. · PI Felix Wong · 2023 to 2026
$486k
NCI NIH HHS T32 CA009216NIAID NIH HHS K25 AI168451NIAID NIH HHS R01 AI144369NIAID NIH HHS R01 AI146194
6 · The paper itself

Abstract

There is a need to discover and develop non-toxic antibiotics that are effective against metabolically dormant bacteria, which underlie chronic infections and promote antibiotic resistance. Traditional antibiotic discovery has historically favored compounds effective against actively metabolizing cells, a property that is not predictive of efficacy in metabolically inactive contexts. Here, we combine a stationary-phase screening method with deep learning-powered virtual screens and toxicity filtering to discover compounds with lethality against metabolically dormant bacteria and favorable toxicity profiles. The most potent and structurally distinct compound without any obvious mechanistic liability was semapimod, an anti-inflammatory drug effective against stationary-phase E. coli and A. baumannii. Integrating microbiological assays, biochemical measurements, and single-cell microscopy, we show that semapimod selectively disrupts and permeabilizes the bacterial outer membrane by binding lipopolysaccharide. This work illustrates the value of harnessing non-traditional screening methods and deep learning models to identify non-toxic antibacterial compounds that are effective in infection-relevant contexts.

Indexed as

AnilidesAnti-Bacterial AgentsEscherichia coliGuanidinesBacteriaHydrazonesMicrobial Sensitivity TestsAnilidesAnti-Bacterial AgentsGuanidinesHydrazonessemapimodantibioticsantibiotic tolerancebacterial metabolismdrug discoverymachine learning

Identifiers

PMID38029756
PMCPMC11031330

What OpenQuestion holds

Textmetadata
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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.