The fungal pathogen Candida albicans is surrounded by a cell wall that is the target of caspofungin and other echinocandin antifungals. C. albicans can grow in several morphological forms, notably budding yeast and hyphae. Yeast and hyphal forms differ in cell wall composition, leading us to hypothesize that there may be distinct genes required for yeast and hyphal responses to caspofungin. Mutants in 27 genes reported previously to be caspofungin hypersensitive under yeast growth conditions were all caspofungin hypersensitive under hyphal growth conditions as well. However, a screen of mutants defective in transcription factor genes revealed that Cup9 is required for normal caspofungin tolerance under hyphal and not yeast growth conditions. In a hyphal-defective efg1Δ/Δ background, Cup9 is still required for normal caspofungin tolerance. This result argues that Cup9 function is related to growth conditions rather than cell morphology. RNA-seq conducted under hyphal growth conditions indicated that 361 genes were up-regulated and 145 genes were down-regulated in response to caspofungin treatment. Both classes of caspofungin-responsive genes were enriched for cell wall-related proteins, as expected for a response to disruption of cell wall integrity and biosynthesis. The cup9Δ/Δ mutant, treated with caspofungin, had reduced RNA levels of 40 caspofungin up-regulated genes, and had increased RNA levels of 8 caspofungin down-regulated genes, an indication that Cup9 has a narrow rather than global role in the cell wall integrity response. Five Cup9-activated surface-protein genes have roles in cell wall integrity, based on mutant analysis published previously (PGA31, IFF11) or shown here (ORF19.3499, ORF19.851 or PGA28), and therefore may explain the hypersensitivity of the cup9Δ/Δ mutant to caspofungin. Our findings define Cup9 as a new determinant of caspofungin susceptibility.

中文翻译：

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转录调节因子 Cup9 对白色念珠菌细胞壁完整性的环境条件控制。


真菌病原体白色念珠菌被细胞壁包围，该细胞壁是卡泊芬净和其他棘白菌素抗真菌药的靶标。白色念珠菌可以多种形态生长，尤其是芽殖酵母和菌丝。酵母和菌丝形式的细胞壁组成不同，这使我们推测酵母和菌丝对卡泊芬净的反应可能需要不同的基因。先前报道的 27 个基因中的突变体在酵母生长条件下对卡泊芬净过敏，在菌丝生长条件下也对卡泊芬净过敏。然而，对转录因子基因缺陷突变体的筛选表明，在菌丝而非酵母生长条件下，Cup9 是正常卡泊芬净耐受所必需的。在菌丝缺陷的 efg1Δ/Δ 背景下，正常的卡泊芬净耐受性仍需要 Cup9。这一结果表明 Cup9 功能与生长条件有关，而不是与细胞形态有关。在菌丝生长条件下进行的 RNA-seq 表明，卡泊芬净处理后，361 个基因上调，145 个基因下调。两类卡泊芬净反应基因都富含细胞壁相关蛋白，正如对细胞壁完整性和生物合成破坏的反应所预期的那样。用卡泊芬净处理的 cup9Δ/Δ 突变体降低了 40 个卡泊芬净上调基因的 RNA 水平，并增加了 8 个卡泊芬净下调基因的 RNA 水平，这表明 Cup9 在细胞壁中具有狭窄而非全局的作用诚信回应。根据先前发表的突变体分析（PGA31、IFF11）或此处显示的突变体分析（ORF19.3499、ORF19.3499），五个 Cup9 激活的表面蛋白基因在细胞壁完整性中发挥作用。851 或 PGA28)，因此可以解释 cup9Δ/Δ 突变体对卡泊芬净的超敏性。我们的研究结果将 Cup9 定义为卡泊芬净敏感性的新决定因素。