Visible Photosensitizing Disinfectant Spray for Combating Multidrug-Resistant Candidozyma Auris in Healthcare Settings

Abstract

Developing simple and convenient strategies to eliminate drug-resistant pathogen-transmission routes efficiently is extremely urgent for hospital healthcare. Candidozyma auris (C. auris) is an emerging nosocomial pathogen with multidrug resistance that easily forms biofilms, aggravating the risk of spreading in public places. Herein, a novel visible light-induced disinfectant spray with a boric-acid-functionalized lipophilic cation, TB, was developed. The boronic acid groups enable simultaneous targeting of polysaccharide-rich cell walls and extracellular polymeric substances within biofilms. TB spray achieved a > 99.9% reduction in C. auris with light and reduced biofilm biomass by approximately 85.2%. TB's polysaccharide targeting, pH-enhanced properties, positive charge, and particle size enable it to effectively bind to C. auris in acidic biofilm microenvironments, boosting photodynamic inactivation, collapsing biofilms, and preventing recurrence. It produces reactive oxygen species through Type I and II pathways, ensuring high efficacy even in hypoxic conditions, making it ideal for disinfecting high-touch surfaces. In a rat model of ventilator-associated pneumonia, TB markedly reduced pulmonary C. auris loads by over 100-fold and significantly attenuated lung injury. Furthermore, the breakdown of polysaccharides enhanced the hydrophobicity of both abiotic and biological surfaces, as well as the increased contact angle, inhibiting biofilm adhesion. Multiomics analysis revealed that TB suppressed C. auris by disrupting genes associated with oxidative stress response, ergosterol biosynthesis, and biofilm maintenance. This visible light-induced disinfectant spray holds great potential to combat outbreaks of high-risk pathogens and could revolutionize disinfection practices in healthcare settings.

Keywords

Candidozyma auris / dual-type AIE photosensitizer / hospital-acquired infections / pH-enhanced / polysaccharide

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