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肌球蛋白马达样结构域的几丁质合酶控制烟曲霉对棘白菌素类药物的耐药性。

Chitin synthases with a myosin motor-like domain control the resistance of Aspergillus fumigatus to echinocandins.

机构信息

Departamento de Microbiología y Genética, Universidad de Salamanca, Salamanca, Spain.

出版信息

Antimicrob Agents Chemother. 2012 Dec;56(12):6121-31. doi: 10.1128/AAC.00752-12. Epub 2012 Sep 10.

DOI:10.1128/AAC.00752-12
PMID:22964252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3497188/
Abstract

Aspergillus fumigatus has two chitin synthases (CSMA and CSMB) with a myosin motor-like domain (MMD) arranged in a head-to-head configuration. To understand the function of these chitin synthases, single and double csm mutant strains were constructed and analyzed. Although there was a slight reduction in mycelial growth of the mutants, the total chitin synthase activity and the cell wall chitin content were similar in the mycelium of all of the mutants and the parental strain. In the conidia, chitin content in the ΔcsmA strain cell wall was less than half the amount found in the parental strain. In contrast, the ΔcsmB mutant strain and, unexpectedly, the ΔcsmA/ΔcsmB mutant strain did not show any modification of chitin content in their conidial cell walls. In contrast to the hydrophobic conidia of the parental strain, conidia of all of the csm mutants were hydrophilic due to the presence of an amorphous material covering the hydrophobic surface-rodlet layer. The deletion of CSM genes also resulted in an increased susceptibility of resting and germinating conidia to echinocandins. These results show that the deletion of the CSMA and CSMB genes induced a significant disorganization of the cell wall structure, even though they contribute only weakly to the overall cell wall chitin synthesis.

摘要

烟曲霉有两个几丁质合酶(CSMA 和 CSMB),它们具有肌球蛋白马达样结构域(MMD),呈头对头排列。为了了解这些几丁质合酶的功能,构建并分析了单突变和双突变菌株。尽管突变体的菌丝生长略有减少,但所有突变体和亲本菌株的菌丝中总几丁质合酶活性和细胞壁几丁质含量相似。在分生孢子中,ΔcsmA 菌株细胞壁中的几丁质含量不到亲本菌株的一半。相比之下,令人惊讶的是,ΔcsmB 突变体菌株和 ΔcsmA/ΔcsmB 突变体菌株的分生孢子细胞壁几丁质含量没有任何修饰。与亲本菌株疏水性的分生孢子不同,由于存在覆盖疏水性表面-棒层的无定形物质,所有 csm 突变体的分生孢子都是亲水性的。CSM 基因的缺失也导致休眠和萌发分生孢子对棘白菌素的敏感性增加。这些结果表明,CSMA 和 CSMB 基因的缺失导致细胞壁结构的显著紊乱,尽管它们对细胞壁总几丁质合成的贡献很小。

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本文引用的文献

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Myosin-5, kinesin-1 and myosin-17 cooperate in secretion of fungal chitin synthase.肌球蛋白-5、驱动蛋白-1 和肌球蛋白-17 协同作用于真菌几丁质合酶的分泌。
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The chitin synthase genes chsA and chsC are not required for cell wall stress responses in the human pathogen Aspergillus fumigatus.几丁质合成酶基因 chsA 和 chsC 对于人类病原体烟曲霉的细胞壁应激反应并非必需。
Biochem Biophys Res Commun. 2011 Aug 5;411(3):549-54. doi: 10.1016/j.bbrc.2011.06.180. Epub 2011 Jul 5.
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Atomic force microscopy: a nanoscopic window on the cell surface.原子力显微镜:细胞表面的纳米窗口。
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Fusarium verticillioides chitin synthases CHS5 and CHS7 are required for normal growth and pathogenicity.串珠镰刀菌几丁质合成酶 CHS5 和 CHS7 对于正常生长和致病性是必需的。
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Amino acid divergence between the CHS domain contributes to the different intracellular behaviour of Family II fungal chitin synthases in Saccharomyces cerevisiae.CHS 结构域中的氨基酸差异导致酿酒酵母中 II 型真菌几丁质合成酶的不同细胞内行为。
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The myosin motor domain of fungal chitin synthase V is dispensable for vesicle motility but required for virulence of the maize pathogen Ustilago maydis.真菌几丁质合成酶 V 的肌球蛋白马达结构域对于囊泡运动不是必需的,但对于玉米病原体玉米黑粉菌的毒力是必需的。
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Microbial nanoscopy: a closer look at microbial cell surfaces.微生物纳米显微镜:观察微生物细胞表面的新视角。
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