Apoptosis of Multi-Drug Resistant Candida Species on Microstructured Titanium Surfaces

Abstract

The proportion of hospital-acquired medical device infections caused by pathogenic, multi-drug resistant Candida species occurs in up to 10% of implantations. In this study, a unique antifungal micro-pillared titanium surface pattern is developed, which demonstrates both fungicidal and fungistatic activity, persistently deterring biofilm formation by Candida albicans and multi-drug resistant Candida auris fungi for up to 7 days. The Ti micropillars of 3.5 µm height are fabricated using maskless inductively coupled plasma reactive ion etching. The micro-textured surface consistently kills ≈50% of Candida spp. irreversibly attached cells and prevent the proliferation of the remaining cells by inducing programmed cell death. Proteomic analysis reveals that Candida cells undergo extensive metabolic stress, preventing the transformation from yeast to the filamentous/hyphal cell phenotype that is essential for establishing a typical in vitro biofilm. The mechanical stress imparted following interaction with the micropillars injures attaching cells and induces apoptosis whereby the Candida cells are unable to be revived in a non-stress environment. These findings shed new insight toward the design of durable antifungal surfaces that prevent biofilm formation by pathogenic, multi-drug resistant yeasts.