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NIH4215:一种易发生突变的胺辅性临床Aspergillus fumigatus隔离物

Roberta Peres da Silva¹, Matthias Brock¹

¹University of Nottingham, School of Life Sciences, University Park, Nottingham, United Kingdom.

Frontiers in fungal biology

|September 25, 2023

概括

在药物研究中使用的临床Aspergillus fumigatus菌株NIH4215,被发现是胺辅助性,容易发生突变. 这种易发生突变的性质可能会加速抗真菌耐药性的发展.

科学领域:

医学真菌学医学真菌学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

由Aspergillus fumigatus引起的侵袭性阿斯伯吉洛症是一个重大的治疗挑战.
临床分离物NIH4215经常用于抗真菌药物疗效研究.
最初试图为体内研究创建NIH4215的生物发光记者菌株的尝试由于生长缺陷而失败.

研究的目的:

为了调查Aspergillus fumigatus菌株NIH4215.5.的生长缺陷的原因.
在NIH4215.5菌株中描述胺辅助性基因的基因基础.
开发NIH4215的生物发光记者菌株,用于体内药物疗效研究,并评估其毒性和突变率.

主要方法:

基因分析以确定负责辅食性胺生物合成基因.
基因测序用于识别已识别的基因中的突变.
菌株工程通过引入野生类型基因和删除特定的基因位点 (akuB) 来创建生物发光记者菌株.
使用Galleria mellonella感染模型进行病毒性评估.
通过查化酸耐药性来确定突变率.

主要成果:

菌株NIH4215由于缺陷的nmt1基因,表现出胺辅性,缺少一种必要的铁结合动机中的氨酸密码子.
在NIH4215中成功生成了一种生物发光记者菌株 (ΔakuB),显示出高同源整合效率.
在Galleria mellonella模型中,胺辅和akuB删除没有显著影响毒性.
菌株NIH4215及其衍生物具有较高的突变率,由酸耐药突变的频率增加以及pyrG和pyrE的突变证实.

结论:

胺生物合成对于阿斯伯吉勒斯烟虫的宿主感染是不可或缺的.
菌株NIH4215是一种胺辅助基因,具有显著增加的突变率.
像NIH4215这样易发生突变的菌株可能有助于阿斯伯吉路斯烟草菌中醇耐药性的演变和传播.

关键词:

在DHN-黑色素中.加勒利亚梅罗内拉 (Galleria Mellonella) 是一个城市.这就是为什么 akuBB.生物发光的记者 nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1nmt1 这是自发的突变.乙胺生物合成

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