Polymorphism of polymeric amino acid regions in fungal proteins and correlation with altered echinocandin and azole susceptibility

Abstract

Polymorphism of polymeric amino acid (polyX) regions within fungal proteins represents a potential mechanism for rapid genotypic adaptation to environmental pressures, including antifungal exposure. Polyglutamine (polyQ) was the most abundant repeat in the proteomes of 8 diverse fungal species and was preferentially found in regulatory proteins. In Candida glabrata, polyX polymorphisms were characterized in 36 proteins implicated in azole or echinocandin susceptibility. General transcriptional repressor Tup1A exhibited Q44/Q45 polymorphism, and Hog1 signaling component Ssk2 exhibited N44/N45 polymorphism in phylogenetically matched echinocandin- and azole-susceptible/resistant strains, respectively.