A recyclable and light-triggered nanofibrous membrane against the emerging fungal pathogen Candida auris

The emerging "super fungus" Candida auris has become an important threat to human health due to its pandrug resistance and high lethality. Therefore, the development of novel antimicrobial strategy is essential. Antimicrobial photodynamic therapy (aPDT) has excellent performance in clinical applications. However, the relevant study on antifungal activity and the mechanism involved against C. auris remains scarce. Herein, a recyclable and biodegradable polylactic acid-hypocrellin A (PLA-HA) nanofibrous membrane is newly developed. In vitro PLA-HA-aPDT could significantly reduce the survival rate of C. auris plankton and its biofilms, and the fungicidal effect of the membrane is still significant after four repeated uses. Simultaneously, PLA-HA exhibits good biocompatibility and low hemolysis. In vivo experiments show that PLA-HA-aPDT can promote C. auris-infected wound healing, reduce inflammatory response, and without obvious toxic side-effects. Further results reveal that PLA-HA-aPDT could increase endogenous reactive oxygen species (ROS) levels, leading to mitochondrial dysfunction, release of cytochrome C, activation of metacaspase, and nuclear fragmentation, thereby triggering apoptosis of C. auris. Compared with HA, PLA-HA shows stronger controllability and reusability, which can greatly improve the utilization efficiency of HA alone. Taken together, the efficacy, safety and antifungal activity make PLA-HA-aPDT a highly promising antifungal candidate for skin or mucous membrane C. auris infection. Author summaryIt is urgent to develop new antifungal strategies to address the problem of Candida auris infection and drug resistance. Previous studies have revealed that antimicrobial photodynamic therapy (aPDT) based on natural products, such as hypocrellin A (HA), is a promising method in clinical applications. However, equivalent studies of aPDT on antifungal activity and its mechanism against C. auris remain scarce. Herein, we successfully prepared a recyclable, biodegradable, and light-driven antifungal PLA-HA nanofibrous membrane through the electrospinning technique. C. auris infection has been treated by aPDT in vitro and in vivo for the first time, especially HA-mediated aPDT. In vitro and in vivo experiments have provided sufficient lines of evidence that PLA-HA is a promising antifungal material for superficial C. auris infections due to its antifungal effect and excellent biocompatibility. Notably, there still remains a very high antifungal activity after utilizing PLA-HA four times. In addition, this study clarifies that the anti-C. auris mechanism of PLA-HA, namely, PLA-HA-mediated aPDT, is attributed to the formation of intracellular ROS, resulting in mitochondrial dysfunction and a decline in the mitochondrial transmembrane potential, releasing cytochrome C from mitochondria to the cytoplasm, promoting the activation of metacaspase, and inducing nuclear condensation and fragmentation of C. auris, thus triggering yeast cell apoptosis. This study lays a foundation for developing new antimicrobial nanofibrous dressings mediated by aPDT and provides an alternative strategy for the treatment of local fungal infectious diseases.