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

Abstract

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.