Post-transcriptional control of antifungal resistance in human fungal pathogens

Global estimates suggest that over 300 million individuals of all ages are affected by serious fungal infections every year, culminating in about 1.7 million deaths. The societal and economic burden on the public health sector due to opportunistic fungal pathogens is quite significant, especially among immunocompromised patients. Despite the high clinical significance of these infectious agents, treatment options are limited with only three major classes of antifungal drugs approved for use. Clinical management of fungal diseases is further compromised by the emergence of antifungal resistant strains. Transcriptional and genetic mechanisms that control drug resistance in human fungal pathogens are well-studied and include drug target alteration, upregulation of drug efflux pumps as well as changes in drug affinity and abundance of target proteins. In this review, we highlight several recently discovered novel post-transcriptional mechanisms that control antifungal resistance, which involve regulation at the translational, post-translational, epigenetic, and mRNA stability levels. The discovery of many of these novel mechanisms has opened new avenues for the development of more effective antifungal treatment strategies and new insights, perspectives, and future directions that will facilitate this process are discussed.