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基因编码区与其内在伏立康唑和氟康唑耐药性之间的关联的分子确认。

Molecular Confirmation of the Linkage between the Gene Coding Region and Its Intrinsic Voriconazole and Fluconazole Resistance.

机构信息

Laboratorio de Micología y Diagnóstico Molecular, Cátedra de Parasitología y Micología, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT, Santa Fe, Argentina.

出版信息

Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.00224-18. Print 2018 Aug.

DOI:10.1128/AAC.00224-18
PMID:29891608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6105841/
Abstract

is the most prevalent causative agent of mucormycosis, an increasingly reported opportunistic fungal infection. These Mucorales are intrinsically resistant to - and -active antifungal azole drugs, such as fluconazole (FLC) and voriconazole, respectively. Despite its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work was to establish if the genes are uniquely responsible for intrinsic voriconazole and fluconazole resistance in these fungal pathogens. Two genes were identified in the genome. We classified them as and based on their sequence similarity with other known fungal genes. Later, we obtained a chimeric strain harboring a functional gene expressed under the regulation of the wild-type promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC hypersusceptibility of the deletion mutant used as the recipient strain. The azole susceptibility patterns of the transformants harboring mimicked exactly the azole susceptibility patterns of this mucormycete. The data presented in this work demonstrate that the coding sequence is uniquely responsible for the azole susceptibility patterns.

摘要

是毛霉病(一种日益报道的机会性真菌感染)最常见的病原体。这些毛霉目真菌对 - 和 - 活性抗真菌唑类药物具有内在抗性,分别为氟康唑(FLC)和伏立康唑。尽管它很重要,但它内在唑类药物抗性的分子机制尚未阐明。这项工作的目的是确定是否 基因是这些真菌病原体固有伏立康唑和氟康唑抗性的唯一原因。在 基因组中鉴定出了两个 基因。根据它们与其他已知真菌 基因的序列相似性,我们将它们归类为 和 。后来,我们获得了一个携带在野生型 启动子和终止子调控下表达的功能性 基因的嵌合 菌株。通过利用作为受体菌株的 缺失突变体对 FLC 高度敏感的新程序,在转化后选择了突变体。携带 的转化体的唑类药物敏感性模式与这种毛霉菌的唑类药物敏感性模式完全相同。本工作中提出的数据表明, 编码序列是唯一负责 唑类药物敏感性模式的原因。

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本文引用的文献

1
Intrinsic short-tailed azole resistance in mucormycetes is due to an evolutionary conserved aminoacid substitution of the lanosterol 14α-demethylase.固有短尾素耐药性在毛霉菌中是由于羊毛固醇 14α-去甲基酶的一个进化保守的氨基酸取代引起的。
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Environmental Triazole Induces Cross-Resistance to Clinical Drugs and Affects Morphophysiology and Virulence of Cryptococcus gattii and C. neoformans.环境三唑类药物诱导对临床药物的交叉耐药性,并影响新型隐球菌和格特隐球菌的形态生理学和毒力。
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Molecular bases of antifungal resistance in filamentous fungi.丝状真菌抗真菌药物耐药性的分子基础。
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Fluconazole-Induced Ploidy Change in Results from the Uncoupling of Cell Growth and Nuclear Division.氟康唑诱导的倍性变化源于细胞生长与核分裂的解偶联。
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Fluconazole Susceptibility in Cryptococcus gattii Is Dependent on the ABC Transporter Pdr11.加氏隐球菌对氟康唑的敏感性取决于ABC转运蛋白Pdr11。
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