Evidence map›Paper›PMID 40481275›Full record

Articlenpj antimicrobials and resistance2025

Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae.

Yasmin M Surani, Matthew E Wand, Pietro Picconi, Michele Di Palma, Riccardo Zenezini Chiozzi, Md Mahbub Hasan, Paolo Andriollo, Stefan Grätz, Kazi S Nahar, Michael Maynard-Smith and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in npj antimicrobials and resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

15 authors.

Yasmin M SuraniUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury, SP4 0JG, Wiltshire, UK.ORCID http://orcid.org/0000-0002-6991-8739
Matthew E WandUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury, SP4 0JG, Wiltshire, UK.
Pietro PicconiInstitute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
Michele Di PalmaDepartment of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35131, Padova, Italy.
Riccardo Zenezini ChiozziUCL Mass Spectrometry Science Technology Platform, Division of Biosciences, Darwin Building, University College London, Gower Street, London, WC1E 6BT, UK.
Md Mahbub HasanInstitute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
Paolo AndriolloInstitute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
Stefan GrätzDepartment of Chemistry, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
Kazi S NaharInstitute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
Michael Maynard-SmithUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury, SP4 0JG, Wiltshire, UK.
Roderich D SüssmuthDepartment of Chemistry, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
Roberto A SteinerDepartment of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35131, Padova, Italy.
Khondaker Miraz RahmanInstitute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. k.miraz.rahman@kcl.ac.uk.
Charlotte K HindUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury, SP4 0JG, Wiltshire, UK.
J Mark SuttonUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury, SP4 0JG, Wiltshire, UK. mark.sutton@ukhsa.gov.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M009513/1Commonwealth Scholarship Commission BDCS-2019-57Department of Health and Social Care NIHR200658UK Health Security Agency 111742
6 · The paper itself

Abstract

Pyrrolobenzodiazepines (PBDs) containing C8-linked aliphatic heterocycles have been developed as a new class of potent antibacterial compounds. They are active against multidrug resistant Gram-negative pathogens, including Klebsiella pneumoniae. When isolates were exposed to PBDs, they acquired resistance, with significant increases in inhibitory concentrations. Resistant strains showed mutations in genes associated with resistance to albicidin, specifically tsx and merR-family regulator albA. Heterologous expression of AlbA in E. coli and introducing the L120Q AlbA resistance-mediating modification into the genome of a sensitive K. pneumoniae strain conferred PBD and albicidin resistance. Proteomic analysis of the resistant strains showed elevated AlbA protein levels compared to isogenic wild-type strains. Crystallographic studies with the antibiotic binding domain of AlbA show binding of KMR-14-14 to the same groove shown to bind albicidin. Given the parallels between these two structurally unrelated compound classes, AlbA may offer resistance to further antibiotics and should be considered in future antibiotic discovery.

Identifiers

PMID40481275
PMCPMC12144233

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Registered trials

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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.