Evidence map›Paper›PMID 41888145›Full record

ArticleNature communications2026

Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope.

Florian Buchholz, Lina M Upterworth, Leif Tueffers, Espen E Groth, Kira Haas, Daniel Schütz, Abigail Savietto Scholz, Aditi Batra, Surajit Pal, Samarpita Banerjee and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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

21 authors.

Florian Buchholz *Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0003-3882-9132
Lina M Upterworth *Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.ORCID http://orcid.org/0009-0000-2632-3957
Leif TueffersDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Espen E GrothLungenClinic Grosshansdorf, Großhansdorf, Germany.ORCID http://orcid.org/0000-0003-0883-6366
Kira HaasDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Daniel SchützDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Abigail Savietto ScholzInstitute for General Microbiology, University of Kiel, Kiel, Germany.
Aditi BatraDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Surajit PalDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Samarpita BanerjeeDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.
Badri N DubeyCSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany.ORCID http://orcid.org/0000-0002-8626-8918
Sören FranzenburgCompetence Centre for Genomic Analysis Kiel, University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0001-6374-4910
Barbara KalsdorfClinical Infectious Disease, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Klaus F RabeLungenClinic Grosshansdorf, Großhansdorf, Germany.
Dennis NurjadiInstitute of Medical Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Jan RuppInstitute of Medical Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany.ORCID http://orcid.org/0000-0001-8722-1233
Dan I AnderssonDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-6640-2174
Holger SondermannCSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany.ORCID http://orcid.org/0000-0003-2211-6234
Marc BramkampInstitute for General Microbiology, University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0002-7704-3266
Roderich RoemhildDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany. roderich.roemhild@ist.ac.at.ORCID http://orcid.org/0000-0001-9480-5261
Hinrich SchulenburgDepartment of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany. hschulenburg@zoologie.uni-kiel.de.ORCID http://orcid.org/0000-0002-1413-913X

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) EXC 2167-390884018Deutsche Forschungsgemeinschaft (German Research Foundation) GRK 2501, project 4.2Leibniz-Gemeinschaft (Leibniz Association) EvoLUNGMax-Planck-Gesellschaft (Max Planck Society) Fellowship
6 · The paper itself

Abstract

Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogen's genomic diversity. This study found that an initial treatment with a β-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a β-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.

Indexed as

Anti-Bacterial AgentsCell MembranePseudomonas aeruginosaAminoglycosidesBacterial Proteinsbeta Lactam AntibioticsCell WallDrug SynergismHumansMicrobial Sensitivity TestsAminoglycosidesAnti-Bacterial AgentsBacterial Proteinsbeta Lactam AntibioticsCpxR protein, Bacteria

Identifiers

PMID41888145
PMCPMC13187417

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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.