Micafungin alters the expression of genes related to cell wall integrity in Candida albicans biofilms

Abstract

We investigated whether treating Candida biofilms with micafungin, an echinocandin that inhibits the synthesis of glucan in the fungal cell wall, alters the expression of genes related to chitin synthesis and degradation in response to cell wall stress. As expected, all four genes encoding chitin synthases-CHS1, CHS2, CHS3, and CHS8-were upregulated by micafungin treatment. Interestingly, of the four genes encoding chitinases, the expression of only CHT2 and CHT3 was markedly downregulat-ed, that of CHT1 was upregulated, and that of CHT4 remained unaltered after micafungin treatment. Thus, the suppression of only two genes associated with chitin degradation, CHT2 and CHT3,may be involved in the tolerance to the cell wall stress caused by micafungin as well as the induction of chitin synthesis. Further, micafungin markedly increased UTR2, which is calcineurin dependent, and CRZ2, which is calcineurin independent. Therefore, gene regulation possibly includes calcineurin-dependent and independent stress responses, though the regulation of genes associated with cell wall chitin has not yet been completely clarified. Our results imply that cell wall stress can be exploited to enhance the efficacy of micafungin.