Sterol C-22 Desaturase ERG5 Mediates the Sensitivity to Antifungal Azoles in Neurospora crassa and Fusarium verticillioides.
Sterol C-22 Desaturase ERG5 Mediates the Sensitivity to Antifungal Azoles in Neurospora crassa and Fusarium verticillioides.
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DOI：
10.3389/fmicb.2013.00127
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发表时间：
2013
影响因子：
5.2
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Sun X;Wang W;Wang K;Yu X;Liu J;Zhou F;Xie B;Li S
抗真菌唑类药物通过干扰羊毛甾醇 14α-去甲基酶来抑制麦角甾醇生物合成。在这项研究中，在粗糙脉孢菌中鉴定出了响应酮康唑治疗的七个上调和四个下调的麦角甾醇生物合成基因。对麦角甾醇生物合成中6个酮康唑上调基因的敲除突变体的唑类敏感性测试表明，仅敲除甾醇C-22去饱和酶ERG5改变了对唑类的敏感性：erg5突变体对唑类过敏，但生长发育没有明显缺陷。相对于野生型，erg5突变体积累了更高水平的麦角5,7-二烯醇，但其14α-甲基化甾醇的水平与野生型相似。 ERG5同源物在真菌界中高度保守。轮枝镰孢erg5的缺失也增加了酮康唑的敏感性，这表明ERG5同源物在唑类耐药中的作用在不同真菌物种中高度保守，抑制ERG5可以减少唑类的使用，从而为药物设计提供新的靶点。
Antifungal azoles inhibit ergosterol biosynthesis by interfering with lanosterol 14α-demethylase. In this study, seven upregulated and four downregulated ergosterol biosynthesis genes in response to ketoconazole treatment were identified in Neurospora crassa. Azole sensitivity test of knockout mutants for six ketoconazole-upregulated genes in ergosterol biosynthesis revealed that deletion of only sterol C-22 desaturase ERG5 altered sensitivity to azoles: the erg5 mutant was hypersensitive to azoles but had no obvious defects in growth and development. The erg5 mutant accumulated higher levels of ergosta 5,7-dienol relative to the wild type but its levels of 14α-methylated sterols were similar to the wild type. ERG5 homologs are highly conserved in fungal kingdom. Deletion of Fusarium verticillioides erg5 also increased ketoconazole sensitivity, suggesting that the roles of ERG5 homologs in azole resistance are highly conserved among different fungal species, and inhibition of ERG5 could reduce the usage of azoles and thus provide a new target for drug design.
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影响因子：
1.9
作者：
LEES, ND;SKAGGS, B;BARD, M
通讯作者：
BARD, M
影响因子：
4.9
作者：
De Backer, MD;Ilyina, T;Vanden Bossche, H
通讯作者：
Vanden Bossche, H
影响因子：
3.6
作者：
Li, Shaojie;Myung, Kyung;Calvo, Ana M.
通讯作者：
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影响因子：
4.9
作者：
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通讯作者：
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影响因子：
5.2
作者：
Morio, Florent;Pagniez, Fabrice;Le Pape, Patrice
通讯作者：
Le Pape, Patrice