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Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens


Vollenweider, Vera; Rehm, Karoline; Chepkirui, Clara; Pérez-Berlanga, Manuela; Polymenidou, Magdalini; Piel, Jörn; Bigler, Laurent; Kümmerli, Rolf (2024). Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens. eLife, 13:RP92493.

Abstract

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here we show that the iron chelating pyoverdines, siderophores produced by environmental Pseudomonas spp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 natural Pseudomonas isolates used against 12 human pathogens uncovered several pyoverdines with particularly high antibacterial properties and distinct chemical characteristics. The most potent pyoverdine effectively reduced growth of the pathogens Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus in a concentration- and iron-dependent manner. Pyoverdine increased survival of infected Galleria mellonella host larvae, and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution combined with whole-genome sequencing revealed reduced potentials for resistance evolution compared to an antibiotic. Thus, pyoverdines from environmental strains could become new sustainable antibacterials against human pathogens.

Abstract

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here we show that the iron chelating pyoverdines, siderophores produced by environmental Pseudomonas spp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 natural Pseudomonas isolates used against 12 human pathogens uncovered several pyoverdines with particularly high antibacterial properties and distinct chemical characteristics. The most potent pyoverdine effectively reduced growth of the pathogens Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus in a concentration- and iron-dependent manner. Pyoverdine increased survival of infected Galleria mellonella host larvae, and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution combined with whole-genome sequencing revealed reduced potentials for resistance evolution compared to an antibiotic. Thus, pyoverdines from environmental strains could become new sustainable antibacterials against human pathogens.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
07 Faculty of Science > Department of Quantitative Biomedicine
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2024
Deposited On:06 Feb 2024 11:56
Last Modified:08 Feb 2024 04:40
Publisher:eLife Sciences Publications Ltd.
ISSN:2050-084X
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/elife.92493.1
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)