Antifungal photodynamic therapy mediated by novel Nano-Photosensitizers reverses azole resistance through ribosome remodeling

Azole resistance has become increasingly severe. Antifungal photodynamic therapy (aPDT) reportedly showed valuable therapeutic potential against resistant infection, but it requires more effective photosensitizer. Candida albicans strain SC5314 and Candida glabrata isolated from the clinical were used in the experiments. Candida was incubated with photosensitizer for 30 minutes and then irradiated by red light (630 nm, 30 min, 60 mw / cm2). We prepared a highly efficient nano-photosensitizer hexyl-aminolevulinate ethosome (HAL-ES). Using highly drug-resistant C. albicans biofilms and clinical strains of Candida glabria, we demonstrated that HAL-ES-aPDT reverses azole resistance and treats infection by inhibiting biofilm formation and down-regulating multidrug-resistant efflux pump expression. Further study showed that zinc homeostasis is the target of antifungal action of HAL-ES-aPDT, and intracellular zinc deficiency triggers ribosome remodeling as a new strategy to reverse azole resistance of Candida. HAL-ES-aPDT reverses azole resistance by triggering intracellular ribosome remodeling