Polymorphism of polymeric amino acid regions in fungal proteins: correlation with altered echinocandin and azole susceptibility [Mechanisms of Resistance]

Polymorphism of polymeric amino acid (polyX) regions within fungal proteins represents a potential mechanism for rapid genotypic adaptation to environmental pressures including antifungal exposure. 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 signalling component Ssk2 exhibited N44/N45, in phylogenetically matched echinocandin and azole, respectively, susceptible/resistant strains.

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