Disruption of protein synthesis as antifungal mode of action by chitosan

The antimicrobial activity of chitosan has been acknowledged for more than 30 years and yet its mode-of-action remains ambiguous. We analyzed chemical–genetic interactions of low-molecular weight chitosan using a collection of ≈ 4600 S. cerevisiae deletion mutants and found that 31% of the 107 mutants most sensitive to chitosan had deletions of genes related primarily to functions involving protein synthesis. Disruption of protein synthesis by chitosan was substantiated by an in vivo β-galactosidase expression assay suggesting that this is a primary mode of antifungal action. Analysis of the yeast gene deletion array and secondary assays also indicate that chitosan has a minor membrane disruption effect — a leading model of chitosan antimicrobial activity.

• Antifungal activity of chitosan was investigated by yeast chemical–genetic screen.
• 31% of chitosan sensitive mutants had deletions related to protein synthesis.
• Protein synthesis disruption by chitosan was confirmed by an in vivo β-gal assay.
• Chitosan also had minor membrane disruption activity with the yeast model.