Membrane-targeting antimicrobial compounds have differential effects on living and artificial yeast membrane models

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 zeta-potential. Iturin and nystatin were the most effective compounds in reducing growth and increasing membrane permeability. zeta-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.