Mechanisms of Drug Resistance in Candida albicans

Abstract

Antifungal drug resistance in Candida albicans started to emerge with the introduction of antifungal agents in the treatment of diseases caused in human by this fungal pathogen. The decreased activity of these drugs in C. albicans as a result of resistance has been observed in different scales for every currently used drug classes. The occurrence of resistance, generally acquired by genetic alterations, can be considered as a natural defense mechanism of C. albicans against drugs introduced by humans. Several other mechanisms contribute to drug efficacy in C. albicans, one of which is being attributed to tolerance. Antifungal tolerance is rather an adaptive mechanism not necessarily requiring genome changes. Even though the incidence of antifungal resistance in C. albicans is still generally low, clinical samples have given the opportunity to dissect resistance mechanisms. Resistance mechanisms have resulted in a significant gain of knowledge in diverse cellular functions and also genome organization. This knowledge can now be implemented in other fields including clinical diagnostics and design of novel drugs or novel therapies. In this chapter, I will not only review the general principles mediating antifungal drug resistance and latest developments, but also update on the mechanisms mediating antifungal tolerance. Moreover, I will illustrate how the understanding of resistance mechanisms can help to establish novel approaches in detecting drug resistance and designing alternative treatment strategies.