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Gene amplifications cause high-level resistance against albicidin in Gram-negative bacteria
Open accessPreprint — published as 10.1371/journal.pbio.3002186 · Paper page
Abstract
Antibiotic resistance is a continuously increasing concern for public health care. Understanding resistance mechanisms and their emergence is crucial for the development of new antibiotics and their effective use. Here, we report the discovery of a gene amplification-based mechanism that imparts an up to 1000-fold increase in resistance levels against the antibiotic albicidin. We show that this mechanism protects Salmonella Typhimurium and Escherichia coli by increasing the copy number of the GyrI-like transcription regulator STM3175 (YgiV) which binds albicidin. X-ray crystallography and molecular docking studies reveal a conserved binding motif 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 convey resistance in pathogens such as Vibrio vulnificus and Pseudomonas aeruginosa .
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Metadata
- Authors
- Saathoff, M., Kosol, S., Semmler, T., Tedin, K., Dimos, N., Kupke, J., Seidel, M., Ghazisaeedi, F., Wolf, S. A., Kuropka, B., Czyszczoń, W., Ghilarov, D., Grätz, S., Heddle, J. G., Loll, B., Süssmuth, R. D., & Fulde, M.
- Affiliations
- Freie Universität Berlin (DE)
- Technische Universität Berlin (DE)
- Robert Koch Institute (DE)
- Jagiellonian University (PL)
- Corresponding author
- Süssmuth, Roderich D.
- Fulde, Marcus
- ORCID
- Venue
- PLoS Biology
- Publisher
- openRxiv
- Published
- 2022-09-15
- Volume
- 21
- Issue
- 8
- Pages
- e3002186-e3002186
- ISSN
- 1544-9173 (ISSN-L)
- PMC
- PMC10414762
- OpenAlex
- W4385727347
- Cited by
- 25
- References
- 1
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 5
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- PLoS Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Publication server of the Robert Koch Institute (Robert Kock Institute) (submittedVersion, cc-by)
- Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- HZB Repository (Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB)) (submittedVersion, other-oa)
- Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
- Funders
- European Commission (261572)
- Deutsche Forschungsgemeinschaft (Project B5, 1027/4-1, FU 1027/4-1, SU 239/18-1, SPP2225, priority program SPP2225 (FU 1027/4-1), CRC1449, 431232613)
- Narodowym Centrum Nauki (2020/39/B/NZ1/02898, 2020/39/B/NZ1/02898 (OPUS 20))
- Humboldt-Universität zu Berlin
- Freie Universität Berlin
- H. Wilhelm Schaumann Stiftung
- Instituto de Física de Cantabria
- Horizon 2020 Framework Programme (675858, 101017567, 777536)
- Helmholtz-Zentrum Berlin für Materialien und Energie
- Leibniz-Gemeinschaft
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- albicidin, antibiotic resistance, gene amplification, transcription regulators, Salmonella typhimurium, Escherichia coli, Vibrio vulnificus, Pseudomonas aeruginosa, Gram-negative bacteria
- MeSH terms
- Anti-Bacterial Agents, Gene Amplification, Gram-Negative Bacteria, Gram-Positive Bacteria, Organic Chemicals, Phylogeny, Xanthomonas, Molecular Docking Simulation
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