Transcriptional Profiling of the Candida auris Response to Exogenous Farnesol Exposure
Ágnes Jakab, Noémi Balla, Ágota Ragyák, Fruzsina Nagy, Fruzsina Kovács, Zsófi Sajtos, Zoltán Tóth, Andrew M. Borman, István Pócsi, Edina Baranyai, László Majoros, Renátó Kovács
Abstract
Candida auris is a dangerous fungal pathogen that causes outbreaks in health care facilities, with infections associated with a high mortality rate. As conventional antifungal drugs have limited effects against the majority of clinical isolates, new and innovative therapies are urgently needed. Farnesol is a key regulator molecule of fungal morphogenesis, inducing phenotypic adaptations and influencing biofilm formation as well as virulence. Alongside these physiological modulations, it has a potent antifungal effect alone or in combination with traditional antifungals, especially at supraphysiological concentrations. However, our knowledge about the mechanisms underlying this antifungal effect against C. auris is limited. This study has demonstrated that farnesol enhances the oxidative stress and reduces the fungal survival strategies. Furthermore, it inhibits manganese, zinc transport, and iron metabolism as well as increases fungal intracellular copper content. In addition, metabolism was modulated toward β-oxidation. These results provide definitive explanations for the observed antifungal effects.