Evidence map›Paper›PMID 37561817›Full record

ArticlePLoS biology2023

Gene amplifications cause high-level resistance against albicidin in gram-negative bacteria.

Mareike Saathoff, Simone Kosol, Torsten Semmler, Karsten Tedin, Nicole Dimos, Johannes Kupke, Maria Seidel, Fereshteh Ghazisaeedi, Micela Condor Jonske, Silver A Wolf and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2023. 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
2.2field-weighted citation impact, top 11% of its field
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, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Environmental resistome-guided development of resistance-tolerant antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Transcriptomic and proteomic ramifications of segmental amplification inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025
    Review
  8. Article
  9. Review
  10. Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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 at 4 institutions in 2 countries.

Mareike SaathoffInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
Simone KosolInstitut für Chemie, Technische Universität Berlin, Berlin, Germany.
Torsten SemmlerRobert Koch-Institute (RKI), MF2-Genome Sequencing and Genomic Epidemiology, Berlin, Germany.
Karsten TedinInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
Nicole DimosInstitute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Johannes KupkeInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
Maria SeidelInstitut für Chemie, Technische Universität Berlin, Berlin, Germany.
Fereshteh GhazisaeediInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
Micela Condor JonskeInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
Silver A WolfRobert Koch-Institute (RKI), MF2-Genome Sequencing and Genomic Epidemiology, Berlin, Germany.
Benno KuropkaInstitute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Wojciech CzyszczońMalopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Dmitry GhilarovMalopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Stefan GrätzInstitut für Chemie, Technische Universität Berlin, Berlin, Germany.
Jonathan G HeddleMalopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Bernhard LollInstitute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Roderich D SüssmuthInstitut für Chemie, Technische Universität Berlin, Berlin, Germany.
Marcus FuldeInstitute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.ORCID 0000-0003-0469-3951
Freie Universität Berlin · DETechnische Universität Berlin · DEJagiellonian University · PLRobert Koch Institute · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibiotic resistance is a continuously increasing concern for public healthcare. Understanding resistance mechanisms and their emergence is crucial for the development of new antibiotics and their effective use. The peptide antibiotic albicidin is such a promising candidate that, as a gyrase poison, shows bactericidal activity against a wide range of gram-positive and gram-negative bacteria. Here, we report the discovery of a gene amplification-based mechanism that imparts an up to 1000-fold increase in resistance levels against albicidin. RNA sequencing and proteomics data show that this novel mechanism protects Salmonella Typhimurium and Escherichia coli by increasing the copy number of STM3175 (YgiV), a transcription regulator with a GyrI-like small molecule binding domain that traps albicidin with high affinity. X-ray crystallography and molecular docking reveal a new conserved motif in the binding groove of the GyrI-like domain that can interact with aromatic building blocks of albicidin. Phylogenetic studies suggest that this resistance mechanism is ubiquitous in gram-negative bacteria, and our experiments confirm that STM3175 homologs can confer resistance in pathogens such as Vibrio vulnificus and Pseudomonas aeruginosa.

Indexed as

Anti-Bacterial AgentsGene AmplificationGram-Negative BacteriaGram-Positive BacteriaMolecular Docking SimulationOrganic ChemicalsPhylogenyXanthomonasalbicidinAnti-Bacterial AgentsOrganic Chemicals

Identifiers

PMID37561817
PMCPMC10414762
OpenAlexW4385727347

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.