Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data.
Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data.
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DOI：
10.1091/mbc.e13-07-0396
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发表时间：
2014-01
影响因子：
3.3
通讯作者：
Ohya Y
中科院分区：
文献类型：
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作者：
Okada H;Ohnuki S;Roncero C;Konopka JB;Ohya Y
为了更好地定义细胞壁结构如何影响形态发生，在用抑制细胞壁合成的不同方面的三种药物处理后，对酵母细胞的形态进行了定量分析。这些药物诱导了相似的效应，包括更宽的颈部和增加的形态变化，以及不同的效应。芽殖酵母的细胞壁是由多种成分组成的刚性结构。为了彻底了解其参与形态发生，我们使用图像分析软件CalMorph定量分析了用抑制细胞壁合成过程中不同过程的药物处理后的细胞形态。用影响细胞壁的药物处理的细胞表现出更宽的颈部和增加的形态变化。衣霉素抑制细胞壁甘露糖蛋白N-糖基化的初始步骤，诱导的形态与α-甘露糖基化缺陷菌株的形态相似。几丁质合成酶抑制剂尼可霉素Z诱导的形态变化类似于几丁质转糖基酶缺陷突变体的形态变化，可能是由于几丁质在锚定β-葡聚糖网络中的关键作用。为了确定棘白菌素B（一种1，3-β-葡聚糖合成酶抑制剂）的作用模式，我们将其诱导的形态与含有1，3-β-葡聚糖合成催化结构域的Fks 1突变体进行了比较。棘白菌素B表现出与在某些fks 1突变体中观察到的相似的形态学效应，具有细胞极性缺陷和葡聚糖合成活性降低，表明棘白菌素B不仅影响1，3-β-葡聚糖合成，还影响另一个功能域。因此，我们的多变量分析揭示了细胞壁成分的离散功能，并增加了我们对抗真菌药物药理学的理解。
To better define how cell wall structure affects morphogenesis, the morphology of yeast cells was analyzed quantitatively after treatment with the three drugs that inhibit different aspects of cell wall synthesis. These drugs induced both similar effects, including broader necks and increased morphological variation, and distinct effects. The cell wall of budding yeast is a rigid structure composed of multiple components. To thoroughly understand its involvement in morphogenesis, we used the image analysis software CalMorph to quantitatively analyze cell morphology after treatment with drugs that inhibit different processes during cell wall synthesis. Cells treated with cell wall–affecting drugs exhibited broader necks and increased morphological variation. Tunicamycin, which inhibits the initial step of N-glycosylation of cell wall mannoproteins, induced morphologies similar to those of strains defective in α-mannosylation. The chitin synthase inhibitor nikkomycin Z induced morphological changes similar to those of mutants defective in chitin transglycosylase, possibly due to the critical role of chitin in anchoring the β-glucan network. To define the mode of action of echinocandin B, a 1,3-β-glucan synthase inhibitor, we compared the morphology it induced with mutants of Fks1 that contains the catalytic domain for 1,3-β-glucan synthesis. Echinocandin B exerted morphological effects similar to those observed in some fks1 mutants, with defects in cell polarity and reduced glucan synthesis activity, suggesting that echinocandin B affects not only 1,3-β-glucan synthesis, but also another functional domain. Thus our multivariate analyses reveal discrete functions of cell wall components and increase our understanding of the pharmacology of antifungal drugs.