Molecular types of Cryptococcus neoformans and Cryptococcus gattii in Western Australia and correlation with antifungal susceptibility

Abstract

Cryptococcus neoformans and Cryptococcus gattii species complexes have a worldwide distribution; however, there is geographical variation in the prevalence of different molecular types. Additionally, antifungal susceptibility differences between molecular types have been demonstrated. This study investigates the distribution of cryptococcal molecular types among human clinical isolates over a 10-year period from a Western Australian population. Molecular type was determined based on polymorphisms in the phospholipase gene locus identified through amplification and sequencing. Minimum inhibitory concentrations (MICs) were identified for fluconazole, 5-fluorocytosine, posaconazole, itraconazole, voriconazole, and amphotericin B. Most isolates were C. neoformans complex (42) of which over half were molecular type VNI (22) followed by VNII (20). Among the remaining C. gattii complex (13) the majority were VGI (11) with VGII (2) uncommonly found. All isolates demonstrated low MICs to antifungal agents including fluconazole. Geometric mean MIC values against 5-fluorocytosine for VNI (1.741mg/l) were significantly higher than those for VGI (0.47mg/l, P = .002). Similarly fluconazole geometric mean MICs against fluconazole for VNI (2.3mg/l) were significantly higher than VNII (0.87mg/l, P = .036). These data reveal the presence of four molecular types (VNI, VNII, VGI and VGII) within clinical Western Australian cryptococcal isolates and, while elevated antifungal MICs were not encountered, significant molecular type dependent differences in susceptibility were found.