Contrasting Biofilm-Modulating Effects of Polymeric Quaternary Ammonium Compounds on the Pathogenic Yeasts Candida albicans, Candidozyma auris, and Candida parapsilosis.

Quaternary ammonium compounds (QACs), particularly in polymeric form (polyQACs), offer a broad spectrum of antimicrobial activity, e.g., via electrostatic membrane interaction. On the other hand, adamantane derivatives are notable for their rigid, lipophilic structure and exhibit a broad spectrum of biological activities. In this multidisciplinary study, we report the synthesis of three structurally defined and related polyQACs with and without azaadamantane units differing primarily in hydrophilicity and flexibility. We demonstrate that one of these compounds, poly-(vinylbenzyltrimethylammonium chloride) 3, displays biofilm inhibition properties against the pathogenic fungi Candidozyma auris and Candida parapsilosis, whereas the remaining compounds predominantly enhance their biofilm formation. Remarkably, all compounds potentiate the biofilm formation of Candida albicans by up to 838% on glass surfaces and even 26-fold on polystyrene. Despite these substantial effects on biofilm biomass, planktonic cell viability remained unaffected. A tentative model for the structure-property relation between the polyQACs and biofilm formation is proposed. Although further research is needed to fully understand the biofilm-potentiating properties of these polymers, these findings may already pave the way for new diagnostic approaches and innovative treatment strategies.