Evidence map›Paper›PMID 41023239›Full record

ArticleNature microbiology2025

Polymyxin B lethality requires energy-dependent outer membrane disruption.

Carolina Borrelli, Edward J A Douglas, Sophia M A Riley, Aikaterini Ellas Lemonidi, Gerald Larrouy-Maumus, Wen-Jung Lu, Boyan B Bonev, Andrew M Edwards, Bart W Hoogenboom

Abstract read
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. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Disruption ofVirulence · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026
    Review
  11. Polymyxin heteroresistance inJournal of medical microbiology · 2026
    Article
  12. Article
  13. Essential fatty acids disrupt the mycolic acid-rich cell envelope of clinicalFrontiers in cellular and infection microbiology · 2026
    Article
  14. Review
  15. BacterialBiosensors · 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

9 authors.

Carolina BorrelliCentre for Bacterial Resistance Biology, Imperial College London, London, UK.ORCID http://orcid.org/0009-0007-9154-9507
Edward J A DouglasCentre for Bacterial Resistance Biology, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-5892-8539
Sophia M A RileyCentre for Bacterial Resistance Biology, Imperial College London, London, UK.
Aikaterini Ellas LemonidiCentre for Bacterial Resistance Biology, Imperial College London, London, UK.
Gerald Larrouy-MaumusCentre for Bacterial Resistance Biology, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-6614-8698
Wen-Jung LuSchool of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.ORCID http://orcid.org/0009-0004-3972-9074
Boyan B BonevSchool of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.ORCID http://orcid.org/0000-0001-7156-2412
Andrew M EdwardsCentre for Bacterial Resistance Biology, Imperial College London, London, UK. a.edwards@imperial.ac.uk.ORCID http://orcid.org/0000-0002-7173-7355
Bart W HoogenboomLondon Centre for Nanotechnology, University College London, London, UK. b.hoogenboom@ucl.ac.uk.ORCID http://orcid.org/0000-0002-8882-4324

Funding

RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/R000042/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/X000370/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/X001547/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/X002446/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/Y003667/1RCUK | Engineering and Physical Sciences Research Council (EPSRC) EP/K031953/1RCUK | Engineering and Physical Sciences Research Council (EPSRC) EP/S023259/1Science Foundation Ireland (SFI) EP/S023259/1Wellcome TrustWellcome Trust (Wellcome) 227923/Z/23/Z
6 · The paper itself

Abstract

Polymyxin antibiotics target lipopolysaccharides (LPSs) in both membranes of the bacterial cell envelope, leading to bacterial killing through a poorly defined mechanism. Here we demonstrate that metabolic activity is essential for the lethality of clinically relevant doses of polymyxin B (PmB) and leverage this insight to determine its mode of action. PmB killed exponential-phase Escherichia coli but did not eliminate stationary-phase cells unless a carbon source was available. Antibiotic lethality correlated with surface protrusions visible by atomic force microscopy and LPS loss from the outer membrane via processes that required LPS synthesis and transport but that were blocked by the MCR-1 polymyxin resistance determinant. While energy-dependent outer-membrane disruption was not directly lethal, it facilitated PmB access to the inner membrane, which the antibiotic permeabilized in an energy-independent manner, leading to cell death. This work reveals how metabolic inactivity confers tolerance of an important, membrane-targeting antibiotic.

Indexed as

Anti-Bacterial AgentsBacterial Outer MembraneEscherichia coliPolymyxin BCell MembraneDrug Resistance, BacterialEscherichia coli ProteinsLipopolysaccharidesMicrobial Sensitivity TestsAnti-Bacterial AgentsEscherichia coli ProteinsLipopolysaccharidesMCR-1 protein, E coliPolymyxin B

Identifiers

PMID41023239
PMCPMC12578643

What Socratic 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 Socratic graph.