Antifungal Resistance in Non-fumigatus Aspergillus Species

Abstract

This review provides an in-depth exploration of antifungal resistance in non-fumigatus Aspergillus species, mainly focusing on acquired resistance. The available data have been compiled and sometimes re-analysed. It highlights the increasing prevalence of resistance in non-fumigatus species belonging to Flavi, Terrei, Nigri, and Nidulantes Aspergillus sections, offering a detailed analysis of resistance detection methods and the global distribution of resistant strains. The review also thoroughly examines the molecular mechanisms behind resistance and raises key unresolved issues, such as the factors contributing to resistance selection and the clinical implications of in vitro resistance. Additionally, it addresses the challenges of treating infections caused by resistant Aspergillus species and cryptic species and discusses current and future strategies relying on combination therapy and newly developed antifungals. The conclusion emphasises the need for further research into resistance mechanisms and alternative treatments to address the rising threat of antifungal resistance in Aspergillus species.

Keywords: Aspergillus flavus; Aspergillus nidulans; Aspergillus niger; Aspergillus terreus; non‐fumigatus Aspergillus; antifungal resistance; mechanism of resistance.

FIGURE 1

Schematic representation of the A. flavus CYP51 genes showing all mutations leading to amino acid substitutions previously reported in the literature. Sequences were retrieved from Genbank. Green: substitutions only found in susceptible strains; red: reported only in resistant strains, blue: reported in both resistant and susceptible strains, black: reported in unknown phenotype. A: CYP51A, B: CYP51B, and C: CYP51C.