Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi

Abstract

Opportunistic fungal pathogens can cause a diverse range of diseases in humans. The increasing rate of fungal infections caused by strains that are resistant to commonly used antifungals results in difficulty to treat diseases, with accompanying high mortality rates. Existing and newly emerging molecular resistance mechanisms rapidly spread in fungal populations and need to be monitored. Fungi exhibit a diversity of mechanisms to maintain physiological resilience and create genetic variation; processes which eventually lead to the selection and spread of resistant fungal pathogens. To prevent and anticipate this dispersion, the role of evolutionary factors that drive fungal adaptation should be investigated. In this review, we provide an overview of resistance mechanisms against commonly used antifungal compounds in the clinic and for which fungal resistance has been reported. Furthermore, we aim to summarize and elucidate potent generators of genetic variability across the fungal kingdom that aid adaptation to stressful environments. This knowledge can lead to recognizing potential niches that facilitate fast resistance development and can provide leads for new management strategies to battle the emerging resistant populations in the clinic and the environment.

Keywords: Adaptation; Antifungal compounds; Antifungal resistance mechanisms; Aspergillus spp.; Candida spp.; Cryptococcus spp.; Mutation rate; Reproduction.