Point Mutations and Membrane-targeting Antifungal Resistance in Aspergillus fumigatus and Other Non-Candida Species

GARCIA, GUILLERMO

Antifungals: From Genomics to Resistance and the Development of Novel Agents

Caister Academic Press

Lugar: Norfolk; Año: 2015; p. 27 - 53

Invasive fungal infections are occurring with an increasing frequency. The management of these infections is challenging and the mortality is high. These facts make clinicians to indiscriminately use antifungal agents to treat and prevent fungal infections. The increased use of these drugs has resulted in the development of resistance. Antifungal resistance is linked with different molecular mechanisms including alteration in drug target, reduction of the intracellular concentration of the drug, overexpression of the drug target, etc. The aim of this chapter is to summarize the mechanisms of intrinsic and acquired resistance to ergosterol biosynthesis inhibitors and polyenes in Aspergillus fumigatus and other non-Candida species due to point mutations in enzymes participating in ergosterol biosynthesis pathways. This chapter will focus mainly in azole drugs since azole resistance is one of the main problems that modern Mycology is facing. A comparison and correlation between yeasts and molds mechanism of resistance will be described and analyzed although it is challenged by the inherent differences existing between these groups of fungi.