Role of charge and hydrophobicity in translocation of cell‐penetrating peptides into Candida albicans cells

Abstract Although the interactions of cell‐penetrating peptides (CPPs) with mammalian cells have been widely studied, much less is known about their interactions with fungal cells. To study how the properties of CPPs affect translocation into fungal cells, we designed variants of the peptides pVEC and SynB with altered levels of charge and hydrophobicity and evaluated the translocation of the variants into the important human fungal pathogen Candida albicans. Charge played a greater role in translocation efficacy of the peptides than hydrophobicity, with a higher net positive charge leading to higher level of translocation into C. albicans and a higher level of cytosolic localization. Hydrophobicity had little effect on translocation efficacy, but a low level of hydrophobicity did lead to increased vacuolar localization and an energy‐dependent translocation mechanism. Our results suggest that CPPs can be designed for desired levels of cargo delivery into fungal cells and for desired translocation mechanisms.