Mechanisms of antifungal resistance

Abstract

Fungal pathogens cause recurrent infections and life-threatening diseases that require appropriate therapy. Antifungal resources are rather restricted, and the emergence of antifungal resistance among pathogenic fungi has increased over the last decades. Classical targets for antifungals aim mostly at characteristic components of fungal cell membrane and cell wall, including ergosterol, β-1,3-d-glucan, chitin, and mannoproteins. Resistant fungi have been described for all antifungal classes. Fungal genomic plasticity and robust metabolic response provide effective mechanisms to tolerate therapeutical doses. The strategies to circumvent antifungal resistances are limited because of the similarity of fungal structures and physiology to those in plants and animals, including humans. The targets for novel breakthrough therapies seem to be related to the complex signaling pathways that regulate the genes involved in cell wall maintenance. Blocking the stress signals from surface sensors to the nucleus would impede the fungal successful response to antifungals.