FKS2 and FKS3 genes of opportunistic human pathogen Candida albicans influence echinocandin susceptibility [PublishAheadOfPrint]

Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous FKS genes that are evolutionary conserved. One of these, the essential gene FKS1, encodes the catalytic subunit of glucan synthase (GS) that is the target of echinocandin drugs and also serves as site of drug resistance. The two other GS-encoding genes, FKS2 and FKS3, are also expressed but their role in resistance is considered unimportant. However, we report here that expression of FKS1 is upregulated in strains lacking either FKS2 or FKS3. Furthermore, in contrast to what is observed in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs and, consistently, are tolerant to cell wall damaging agents. Our data indicate that C. albicans FKS2 and FKS3 can act as negative regulators of FKS1, thereby influencing echinocandin susceptibility.

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