Confronting antifungal resistance, tolerance, and persistence: Advances in drug target discovery and delivery systems

Human pathogenic fungi pose a serious threat to human health and safety. Unfortunately, the limited number of antifungal options is exacerbated by the continuous emergence of drug-resistant variants, leading to frequent drug treatment failures. Recent studies have also highlighted the clinical importance of other modes of fungal survival of antifungal treatment, including drug tolerance and persistence, pointing to the complexity of the fungal response to antifungal drugs. A lack of understanding of the fungal drug response has hampered the identification of new targets, the development of alternative antifungal strategies and the design of appropriate delivery systems. In this review we summarize recent advances in the study of antifungal resistance, tolerance and persistence, with an emphasis on promising drug targets and drug delivery systems that may yield important insights into the development of new or improved antifungal therapies against fungal infections.