Molecular bases of antifungal resistance in filamentous fungi

Abstract

Invasive mould infections due to Aspergillus spp., Fusarium spp., Scedosporium spp. and other filamentous fungi remain a significant cause of morbidity and mortality in immunocompromised patients. Antifungal therapy is required for successful patient management; however, limited antifungal drugs as well as the emergence of drug resistance pose a challenge to clinicians for effective management of these diseases. The evolution of multidrug-resistant strains owing to selective pressure as well as intrinsically-resistant pathogenic species are a major concern. Thus, it is necessary to gain a better insight into the antifungal resistance mechanisms and their clinical impact. So far, the resistance mechanisms responsible for acquired azole resistance include alteration of the drug target and its overexpression, biofilm formation and efflux pump upregulation. However, mechanisms responsible for polyene and echinocandin resistance are less understood in filamentous moulds, primarily due to incomplete correlation between in vitro susceptibility and clinical response to treatment. The present review gives an insight into the mechanisms implicated in resistance to different classes of antifungal agents both in human and plant pathogenic filamentous fungi. Furthermore, the spectrum of antifungal resistance in these filamentous fungi is highlighted.