Echinocandin Resistance in Clinical Candida glabrata Isolates.

GARCIA-EFFRON, GUILLERMO; PARK, STEVEN; LEE, SAMUEL A.; PERLIN, DAVID S.

Jersey city (EEUU)

Congreso; 9th ASM Conference on Candida and Candidiasis.; 2008

Background: Mutations in two FKS-related genes (FKS1 and FKS2) encoding beta-1,3 Glucan synthase (GS) enzymes have been linked to echinocandin resistance (ER). However, in C. glabrata there was only one report of ER and it was linked to a F625Y substitution in the FKS2p (equivalent to F641 aa. in C. albicans FKS1p). The aim of this study was to analyze a large collection (n=27) of ER C. glabrata establishing the prevalence of fks mutations and its relationship with the GS inhibition by the different echinocandin drugs. 96 % of the ER C. glabrata strains showed characteristic mutations in hot-spot regions of FKSp (19 strains showed a FKS1 mutation, 7 in FKS2 and 1 has mutations in both genes). Substitutions at the S663 position in Fks1p (equivalent to 645 in C. albicans) was the most common mutation found in these strains (33 %). FKS1p substitutions are the most prevalent in ER C. glabrata. FKS2p mutations have lower effect on GS IC50 values (2- to 10-fold lower). The results obtained with one strain showing high ECD MIC but no mutations suggest that there is an other possible ER mechanism in C. glabrata.