PreprintCited by 25Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyAntimicrobial Resistance in Staphylococcus

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

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Preprint — 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
Venue
PLoS Biology
Publisher
openRxiv
Published
2022-09-15
Volume
21
Issue
8
Pages
e3002186-e3002186
ISSN
1544-9173 (ISSN-L)
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
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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