Antimicrobial Agents and Chemotherapy vol:58 pages:3697-3707
Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus, characterised by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low micromolar range. These tyrocidines were also able to prevent C. albicans biofilm formation in vitro. Studies with the membrane impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilisation and rapid lysis of model fungal membranes containing phoshatitydcholine and ergosterol (70:30) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm eradicating activity in combination with two key antifungal drugs, amphotericin B or caspofungin. Using a Caenorhabditis elegans infection model, tyrocidine A could potentiate the activity of caspofungin. Tyrocidines therefore present promising candidates for further research as antifungal drugs and as agents for combinatorial treatment.