Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Jpn J Infect Dis. 2010 Sep;63(5):355-7.
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.
我们研究了抗真菌药物米卡芬净是否通过抑制真菌细胞壁中葡聚糖的合成来改变与细胞应激相关的几丁质合成和降解相关基因的表达。正如预期的那样，编码几丁质合酶的四个基因 CHS1、CHS2、CHS3 和 CHS8 均被米卡芬净处理上调。有趣的是，在编码几丁质酶的四个基因中，只有 CHT2 和 CHT3 的表达明显下调，CHT1 的表达上调，而 CHT4 在米卡芬净处理后保持不变。因此，与几丁质降解相关的两个基因（CHT2 和 CHT3）的抑制可能与米卡芬净引起的细胞壁应激以及几丁质合成的诱导有关。此外，米卡芬净明显增加了依赖钙调神经磷酸酶的 UTR2 和不依赖钙调神经磷酸酶的 CRZ2。因此，基因调控可能包括钙调神经磷酸酶依赖和非依赖的应激反应，尽管与细胞壁几丁质相关的基因调控尚未完全阐明。我们的结果表明，细胞应激可以被用来增强米卡芬净的疗效。
