Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG-CoA Reductase.
Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG-CoA Reductase.
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DOI：
10.3201/eid2410.180730
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发表时间：
2018-10
影响因子：
11.8
通讯作者：
Kamei K
中科院分区：
文献类型：
--
作者：
Hagiwara D;Arai T;Takahashi H;Kusuya Y;Watanabe A;Kamei K
最近，耐唑烟曲霉的增加是一个全球性的问题。鉴定赋予唑类耐药的突变对于开发快速诊断和有效药物治疗的新方法至关重要。我们筛选了A。烟曲霉临床分离株的新突变赋予唑耐药性。我们比较了cyp51A（非cyp51A）无突变的敏感和耐药菌株的基因组序列，发现hmg1和erg6突变参与麦角甾醇生物合成。在不同遗传背景的唑类耐药菌株中，我们也发现了这些基因的新突变。与敏感菌株相比，hmg1突变的耐药菌株细胞内麦角固醇水平升高。这一发现支持了麦角固醇水平是对任何种类唑类耐药性的决定因素的概念。多株唑类耐药菌株hmg1基因突变，表明该突变广泛存在于非cyp51A唑类耐药菌株中。烟熏。
The recent increase in azole-resistant Aspergillus fumigatus is a global concern. Identifying the mutations that confer azole resistance is essential for developing novel methods for prompt diagnosis and effective drug treatment. We screened A. fumigatus clinical isolates for novel mutations conferring azole resistance. We compared the genomic sequences of susceptible and resistant isolates without mutations in cyp51A (non-cyp51A) and found mutations in hmg1 and erg6 involved in ergosterol biosynthesis. We also found the novel mutations in these genes in azole-resistant isolates with different genetic backgrounds. The resistant isolates with mutations in hmg1 showed increased intracellular ergosterol levels compared with susceptible isolates. This finding supports the concept that the ergosterol level is a determinant for resistance to any class of azoles. Multiple isolates with increased resistance to azole possessed a mutation in hmg1, indicating that this mutation is widely present in non-cyp51A azole-resistant A. fumigatus.