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Membrane-targeting antimicrobial compounds have differential effects on living and artificial yeast membrane models
Jennifer I Villacres1, Olivia Luong1, Michael Shaikhet2
1Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.
Abstract:
The stability of the plasma membrane is crucial for cell viability and disruptions in membrane stability can significantly impact cell function. Antimicrobial compounds targeting fungal membranes are required as novel alternatives to current resistance-prone fungicides. Six antimicrobials were assessed using the yeast Saccharomyces cerevisiae in living and artificial membrane models to gain insight into their efficacy and mechanistic activity. Antimicrobial-treated yeast cultures were monitored for growth inhibition and cell membrane permeability. Liposomes prepared from yeast polar lipids were used to examine the impact of the antimicrobials on size, polydispersity, and ζ-potential. Iturin and nystatin were the most effective compounds in reducing growth and increasing membrane permeability. ζ-Potential measurements indicated that iturin caused reduced stability, whereas there were no changes in stability with nystatin. Daptomycin and fengycin did not affect growth or permeability, but reduced stability. Nisin inhibited growth but did not affect stability. Surfactin was the only tested compound to increase stability. Results indicate that antimicrobials known to target biomembranes had variable effects, with lipid membrane components playing a role in antifungal outcome and mechanistic activity.
Insights
Novel antifungal compounds targeting fungal membranes show varied efficacy. Iturin and nystatin effectively inhibited yeast growth and increased membrane permeability, with iturin impacting membrane stability.
Area of Science:
- Biochemistry
- Microbiology
- Pharmacology
Background:
- Plasma membrane stability is vital for cell viability.
- Fungal membrane-targeting antimicrobials are needed due to fungicide resistance.
- Understanding antimicrobial mechanisms is key to developing new antifungal agents.
Purpose of the Study:
- To assess the efficacy and mechanistic activity of six antimicrobials against Saccharomyces cerevisiae.
- To investigate the impact of these compounds on yeast cell membrane permeability and stability.
- To evaluate antimicrobial effects using both living yeast and artificial liposome models.
Main Methods:
- Yeast growth inhibition and cell membrane permeability assays were performed.
- Liposomes from yeast polar lipids were used to analyze changes in size, polydispersity, and zeta potential.
- Six distinct antimicrobial compounds were tested for their effects.
Main Results:
- Iturin and nystatin were most effective in inhibiting yeast growth and increasing membrane permeability.
- Iturin reduced membrane stability, while nystatin did not alter it.
- Other tested compounds (daptomycin, fengycin, nisin, surfactin) exhibited varied effects on growth, permeability, and stability.
Conclusions:
- Antimicrobials targeting biomembranes display diverse effects on fungal cells.
- Yeast lipid membrane components influence antifungal outcomes and mechanisms.
- Further research into specific antimicrobial-membrane interactions is warranted.
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