Efg1 Controls Caspofungin-Induced Cell Aggregation of Candida albicans through the Adhesin Als1
Efg1 Controls Caspofungin-Induced Cell Aggregation of Candida albicans through the Adhesin Als1
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DOI：
10.1128/ec.05187-11
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发表时间：
2011-12-01
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影响因子：
--
通讯作者：
Kuchler, Karl
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作者：
Gregori, Christa;Glaser, Walter;Kuchler, Karl
棘白菌素类药物如卡泊芬净（CASP）、米卡芬净和阿尼芬净通过阻断Fks 1介导的β-葡聚糖沉积到细胞表面来抑制真菌细胞壁的生物合成。念珠菌已成为治疗由几种真菌物种引起的危及生命的疾病的合适药物，包括对人类致病的白色念珠菌。在这里，我们提出了一种新的CASP诱导的絮凝表型的C。白色念珠菌，其在CASP存在下形成大细胞聚集体。高浓度的糖（例如甘露糖或葡萄糖）抑制CASP诱导的絮凝并提高C.白色念珠菌细胞暴露于CASP。值得注意的是，C.白念珠菌细胞与CASP的结合触发粘附素ALS 1的Efg 1依赖性表达，并诱导琼脂平板上的侵袭性生长。事实上，缺乏Efg 1或Als 1的细胞显示出强烈减弱的CASP诱导的絮凝，并且Efg 1的缺乏导致显著的CASP超敏性。另一方面，CASP诱导的侵袭性生长在缺乏Efg 1的细胞中增强。因此，CASP压力驱动Efg 1依赖性反应，表明这种多功能的转录调节因子，这是否则参与的表达，白色到不透明的开关，和毒力，也调节细胞壁重塑后CASP的挑战。总之，我们的数据表明CASP诱导的细胞壁损伤激活Efg 1与已知的细胞完整性应激信号通路并行，以协调细胞壁重塑。
Echinocandin drugs such as caspofungin (CASP), micafungin, and anidulafungin inhibit fungal cell wall biogenesis by blocking Fks1-mediated beta-glucan deposition into the cell surface. Candins have become suitable drugs to treat life-threatening diseases caused by several fungal species, including Candida albicans, that are pathogenic for humans. Here, we present the discovery of a novel CASP-induced flocculation phenotype of C. albicans, which formed large cell aggregates in the presence of CASP. High concentrations of sugars such as mannose or glucose inhibit CASP-induced flocculation and improve survival of C. albicans cells exposed to CASP. Notably, exposure of C. albicans cells to CASP triggers Efg1-dependent expression of the adhesin ALS1 and induces invasive growth on agar plates. Indeed, cells lacking either Efg1 or Als1 show strongly diminished CASP-induced flocculation, and the absence of Efg1 leads to marked CASP hypersensitivity. On the other hand, CASP-induced invasive growth is enhanced in cells lacking Efg1. Hence, CASP stress drives an Efg1-dependent response, indicating that this multifunctional transcriptional regulator, which is otherwise involved in filamentation, white-to-opaque switching, and virulence, also modulates cell wall remodeling upon CASP challenge. Taken together, our data suggest that CASP-induced cell wall damage activates Efg1 in parallel with the known cell integrity stress signaling pathway to coordinate cell wall remodeling.