Candida albicans Sfl2, a temperature-induced transcriptional regulator, is required for virulence in a murine gastrointestinal infection model.
Candida albicans Sfl2, a temperature-induced transcriptional regulator, is required for virulence in a murine gastrointestinal infection model.
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DOI：
10.1111/j.1567-1364.2010.00710.x
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发表时间：
2011-03
影响因子：
3.2
通讯作者：
Wenjie Song;Huafeng Wang;Jiangye Chen
中科院分区：
文献类型：
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作者：
Wenjie Song;Huafeng Wang;Jiangye Chen
许多转录调节因子在人类白色念珠菌的形态发生中起作用。最近，白色念珠菌Sfl1的同源序列Sfl2已被证明是菌丝发育所必需的。在这篇报道中，我们发现Sfl2和Sfl1一样，可以补充酿酒酵母Sfl1突变体的表型，并且绿色荧光蛋白标记的Sfl2定位于白色念珠菌酵母和菌丝细胞的细胞核中，反映了它作为转录调节剂的作用。在白色念珠菌中，SFL2在高生长温度（37°C）下在转录和翻译水平上均被诱导表达。SFL2的缺失在高温下破坏了丝状结构，而SFL2的过表达在低温下促进了丝状结构的生长。sfl2激活的菌丝发育需要在好氧条件下Efg1和Flo8的存在。因此，在白色念珠菌中，与抑制丝状生长的Sfl1相反，Sfl2是丝状生长的激活剂。嵌合Sfl蛋白的功能分析表明，白色念珠菌Sfl1和Sfl2的相反作用主要由其热休克因子结构域介导。此外，在小鼠胃肠道定植和传播模型中，SFL2的缺失降低了毒力，表明SFL2对念珠菌病胃肠道模型的毒力很重要。我们的研究结果为Sfl2在白色念珠菌形态发生和发病机制中的功能提供了新的见解。
Many transcriptional regulators play roles in morphogenesis of the human pathogen Candida albicans. Recently, Sfl2, a sequence homolog of C. albicans Sfl1, has been shown to be required for hyphal development. In this report, we show that, like Sfl1, Sfl2 could complement the phenotypes of the Saccharomyces cerevisiae sfl1 mutant, and green fluorescent protein-tagged Sfl2 localized in the nuclei of both yeast and hyphal cells in C. albicans, reflecting its role as a transcriptional regulator. In C. albicans, SFL2 expression was induced at a high growth temperature (37 °C) at both transcriptional and translational levels. The deletion of SFL2 impaired filamentation at a high temperature, whereas the overexpression of SFL2 promoted filamentous growth at a low temperature. Sfl2-activated hyphal development needs the existence of Efg1 and Flo8 under aerobic conditions. Thus, in contrast to Sfl1, which represses filamentation, Sfl2 acts as an activator of filamentous growth in C. albicans. Functional analysis of chimeric Sfl proteins demonstrated that the opposite actions of C. albicans Sfl1 and Sfl2 were mainly mediated by their heat shock factor domains. Furthermore, the deletion of SFL2 attenuated virulence in a mouse model of gastrointestinal colonization and dissemination, indicating that Sfl2 is important for virulence in the gastrointestinal model of candidiasis. Our results provide new insights into Sfl2 functions in C. albicans morphogenesis and pathogenesis.