Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, 34134, Republic of Korea.
Department of Life Science, College of Natural Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
J Microbiol. 2021 Oct;59(10):911-919. doi: 10.1007/s12275-021-1326-y. Epub 2021 Sep 7.
Candida albicans is an opportunistic human pathogen that exists as yeast, hyphal or pseudohyphal forms depending on pH, nutrients, and temperature. The morphological transition from yeast to hyphae, which is required for the complete virulence of C. albicans, is controlled by many transcription factors that activate or repress hypha-specific genes. The C. albicans transcriptional factor Cas5, a key regulator of genes involved in cell wall integrity, affects the susceptibility of C. albicans to fluconazole, an inhibitor of ergosterol synthesis. In this study, we found that deletion of CAS5 in C. albicans decreased the expression levels of a set of ergosterol biosynthesis genes, such as ERG2, ERG3, ERG5, ERG6, ERG11, and ERG24, resulting in the accumulation of lanosterol and zymosterol, which are intermediate metabolites in the ergosterol biosynthesis pathway. Interestingly, it was observed that the cas5Δ/Δ mutant could not maintain the yeast form under non-hypha-inducing conditions, while the CAS5-overexpressing cells could not form hyphae under hypha-inducing conditions. Consistent with these observations, the cas5Δ/Δ mutant highly expressed hypha-specific genes, ALS3, ECE1, and HWP1, under non-hypha-inducing conditions. In addition, CAS5 transcription was significantly downregulated immediately after hyphal initiation in the wild-type strain. Furthermore, the cas5Δ/Δ mutant reduced the transcription of NRG1, which encodes a major repressor of hyphal morphogenesis, while Cas5 overexpression increased the transcription of NRG1 under hypha-inducing conditions. Collectively, this study suggests the potential role of Cas5 as a repressor of hypha-specific genes during yeast-form growth of C. albicans.
白色念珠菌是一种机会性人类病原体，根据 pH 值、营养物质和温度的不同，其存在形式为酵母、菌丝或假菌丝。从酵母到菌丝的形态转变是白色念珠菌完全毒力所必需的，它受许多转录因子控制，这些转录因子激活或抑制菌丝特异性基因。白色念珠菌转录因子 Cas5 是参与细胞壁完整性的基因的关键调节剂，它影响白色念珠菌对氟康唑（一种抑制麦角固醇合成的抑制剂）的敏感性。在这项研究中，我们发现白色念珠菌中 CAS5 的缺失降低了一组麦角固醇生物合成基因（如 ERG2、ERG3、ERG5、ERG6、ERG11 和 ERG24）的表达水平，导致羊毛甾醇和酵母甾醇的积累，它们是麦角固醇生物合成途径中的中间代谢物。有趣的是，观察到 cas5Δ/Δ 突变体在非菌丝诱导条件下无法维持酵母形态，而 CAS5 过表达细胞在菌丝诱导条件下无法形成菌丝。与这些观察结果一致，cas5Δ/Δ 突变体在非菌丝诱导条件下高度表达菌丝特异性基因 ALS3、ECE1 和 HWP1。此外，在野生型菌株中，CAS5 转录在菌丝起始后立即显著下调。此外，cas5Δ/Δ 突变体降低了编码菌丝形态发生主要抑制剂的 NRG1 的转录，而 Cas5 过表达在菌丝诱导条件下增加了 NRG1 的转录。总之，这项研究表明 Cas5 在白色念珠菌酵母形态生长过程中可能作为菌丝特异性基因的抑制剂发挥作用。
