Zcf24, a zinc‐finger transcription factor, is required for lactate catabolism and inhibits commensalism in Candida albicans
Zcf24, a zinc‐finger transcription factor, is required for lactate catabolism and inhibits commensalism in Candida albicans
复制标题
DOI：
10.1111/mmi.15015
复制
发表时间：
2022-12
影响因子：
3.6
通讯作者：
Qiangqiang Sun;B. Dong;Dandan Yang;Jing Yu;Tianhao Ren;Tianxu Wang;Lianjuan Yang;Yang Lu;C. Su
中科院分区：
文献类型：
--
作者：
Qiangqiang Sun;B. Dong;Dandan Yang;Jing Yu;Tianhao Ren;Tianxu Wang;Lianjuan Yang;Yang Lu;C. Su
白色念珠菌是人类的正常居民，也是一种流行的真菌病原体。乳酸是一种在许多解剖学小生境中可获得的非发酵碳源，可被C.白色念珠菌作为碳源。然而，参与这一过程的关键监管机构仍然未知。在这里，通过遗传筛选，我们报告了一个转录因子Zcf24的鉴定，这是特别需要的乳酸利用在C。白色念珠菌Zcf 24负责诱导CYB 2，CYB 2是一种编码乳酸脱氢酶的基因，该基因是乳酸催化剂响应乳酸所必需的。染色质免疫沉淀显示，在乳酸生长的细胞中，CYB2启动子上的Zcf24信号显著高于葡萄糖生长的细胞。全基因组转录谱表明，除了CYB2，Zcf24还调节参与脂肪酸β氧化、铁转运和药物转运的基因。令人惊讶的是，删除ZCF 24赋予增强的骨骼健康。这可能归因于zcf24突变体中Crz1激活的β葡聚糖掩蔽。Zcf24的直系同源物在物种中的分布与C.白色念珠菌和一些丝状真菌物种。总之，Zcf 24是迄今为止鉴定的第一个调节C.白念珠菌，它也参与调节念珠菌病。
Candida albicans is a normal resident of humans and also a prevalent fungal pathogen. Lactate, a nonfermentative carbon source available in numerous anatomical niches, can be used by C. albicans as a carbon source. However, the key regulator(s) involved in this process remain unknown. Here, through a genetic screen, we report the identification of a transcription factor Zcf24 that is specifically required for lactate utilization in C. albicans. Zcf24 is responsible for the induction of CYB2, a gene encoding lactate dehydrogenase that is essential for lactate catabolism, in response to lactate. Chromatin immunoprecipitation showed a significantly higher signal of Zcf24 on the CYB2 promoter in lactate‐grown cells than that in glucose‐grown cells. Genome‐wide transcription profiling indicates that, in addition to CYB2, Zcf24 regulates genes involved in the β‐oxidation of fatty acids, iron transport, and drug transport. Surprisingly, deleting ZCF24 confers enhanced commensal fitness. This could be attributed to Crz1‐activated β‐glucan masking in the zcf24 mutant. The orthologs of Zcf24 are distributed in species most closely to C. albicans and some filamentous fungal species. Altogether, Zcf24 is the first transcription factor identified to date that regulates lactate catabolism in C. albicans and it is also involved in the regulation of commensalism.