Micafungin alters the expression of genes related to cell wall integrity in Candida albicans biofilms.
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 downregulated, 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.
Kaneko
Yukihiro
Y
Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. ykaneko@nih.go.jp
Ohno
Hideaki
H
Kohno
Shigeru
S
Miyazaki
Yoshitsugu
Y
D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002473:Cell Wall / Q000187:drug effects / Q000235:genetics; D002687:Chitin Synthase / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D012331:RNA, Fungal / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D015854:Up-Regulation / Q000187:drug effects
D000935:Antifungal Agents; D017931:DNA Primers; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D012331:RNA, Fungal; D002687:Chitin Synthase; D000077551:Micafungin