Molecular Confirmation of the Relationship between Candida guilliermondii Fks1p Naturally Occurring Amino Acid Substitutions and Its Intrinsic Reduced Echinocandin Susceptibility

Abstract

<i>Candida guilliermondii</i> shows intrinsic reduced echinocandin susceptibility. It harbors two polymorphisms (L633M and T634A) in the Fks1p hot spot 1 region. Our objective was to confirm that the reduced echinocandin susceptibility of <i>C. guilliermondii</i> is due to those naturally occurring substitutions. We constructed a <i>Saccharomyces cerevisiae</i> mutant in which a region of the <i>FKS1</i> gene (including hot spot 1) was replaced with that from <i>C. guilliermondii</i> The chimeric mutants showed 32-fold increases in echinocandin MIC values, confirming the hypothesis.