ArticlePLoS biology2023
Gene amplifications cause high-level resistance against albicidin in gram-negative bacteria.
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.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Comparative assessment of annotation tools reveals critical antimicrobial resistance knowledge gaps in Klebsiella pneumoniae.Scientific reports · 2025Article
- Driving factors for beta-lactam resistance gene amplification duringAntimicrobial agents and chemotherapy · 2025Article
- Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae.npj antimicrobials and resistance · 2025Article
- Environmental resistome-guided development of resistance-tolerant antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Transcriptomic and proteomic ramifications of segmental amplification inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synthesis of Derivatives of the Antibiotic Albicidin: The N-Terminal Fragment as Key to Control Potency and Resistance Mediated by the Binding Protein AlbA.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Heteroresistance in Enterobacter cloacae complex caused by variation in transient gene amplification events.npj antimicrobials and resistance · 2025Article
- Epidemiology, mechanisms, and clinical impact of bacterial heteroresistance.npj antimicrobials and resistance · 2025Review
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
- YgiV promoter mutations cause resistance to cystobactamids and reduced virulence factor expression in Escherichia coli.npj antimicrobials and resistance · 2024Article
- Harnessing Gram-negative bacteria for novel anti-Gram-negative antibiotics.Microbial biotechnology · 2024Review
- High prevalence of heteroresistance in Staphylococcus aureus is caused by a multitude of mutations in core genes.PLoS biology · 2024Article
- Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic.Nature communications · 2023Article
- Transcription activation by the resistance protein AlbA as a tool to evaluate derivatives of the antibiotic albicidin.Chemical science · 2023Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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