Mild Heat Stress Affects on the Cell Wall Structure in Candida albicans Biofilm
Mild Heat Stress Affects on the Cell Wall Structure in Candida albicans Biofilm
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DOI：
10.3314/mmj.19-00001
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发表时间：
2019-01-01
影响因子：
1
通讯作者：
Tanaka, Yoshihiko
中科院分区：
文献类型：
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作者：
Ikezaki, Shojiro;Cho, Tamaki;Tanaka, Yoshihiko
我们以前报道过白色念珠菌在模拟发烧的温度升高范围内对轻度热应激反应，并得出结论，轻度热应激增加了抗真菌药物的敏感性。在这项研究中，我们表明，温和的热应力导致的形态变化，菌丝在生物膜形成的过程中。结果表明，轻度热胁迫延长了菌丝期的维持时间。白色念珠菌生物膜虽然从酵母形态到菌丝形态的菌丝变化速率在3小时内达到最大值，但随后，几乎每个细胞在37 ℃下6小时内迅速恢复到酵母生长期，而不是在39 ℃下或在轻度热应激下。电子显微镜观察表明，轻度热胁迫显著增加了菌丝的内细胞壁厚度，同时降低了菌丝的外细胞壁密度。白色念珠菌生物膜为了确定与轻度热应激相关的形态学变化的基因，我们进行了微阵列基因表达分析。在轻度热胁迫条件下，生物膜细胞中有11个基因表达上调，17个基因表达下调。在定量RT-PCR分析中证实了PHR 1基因表达的增加，以应对轻度热应激。突变体上调的PHR 1表达显示出与轻度热应激依赖的抗真菌药物米卡芬净相同的敏感性。我们的研究结果指出了高温可能的治疗效果以及感染期间发热的影响。
We previously reported that Candida albicans responded to mild heat stress in a range of temperature elevations simulating fever, and concluded that mild heat stress increases susceptibility to antifungal drugs. In this study, we show that mild heat stress causes a morphological change in hyphae during the process of biofilm formation. We found that mild heat stress extended the period of hyphal stage maintenance in C. albicans biofilm. Although the rate of hyphal change from yeast form to hyphal form reached the maximum within 3 hr, later, almost every cell quickly reverted to the yeast growth phase within 6 hr at 37 degrees C but not at 39 degrees C, or under mild heat stress. Electron microscopy using a smart specimen preparation technique revealed that mild heat stress significantly increased the thickness of the inner cell wall accompanied by a decrease in density of the outer cell wall in the hyphae of C. albicans biofilm. To identify the gene responsible for the morphological changes associated with mild heat stress, we performed microarray gene expression analysis. Eleven genes were upregulated and 17 genes were downregulated under mild heat stress in biofilm cells. The increased PHR1 gene expression in response to mild heat stress was confirmed in quantitative RT-PCR analysis. The mutant upregulated PHR1 expression showed the same sensitivity against antifungal drug micafungin as dependent on mild heat stress. Our findings point to possible therapeutic effects of hyperthermia as well as to the effect of fever during infections.