Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba, Japan.
Department of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Mycoses. 2021 Nov;64(11):1354-1365. doi: 10.1111/myc.13370. Epub 2021 Sep 29.
Mutations in cyp51A gene are known as main mechanisms of azole resistance in Aspergillus fumigatus, whereas azole-susceptible strains also carry cyp51A mutations (polymorphisms). The polymorphisms found in Europe mainly consist of two combinations of mutations, that is combinations of five single-nucleotide polymorphisms (SNPs) of cyp51A, referred to as cyp51A-5SNPs, and combinations of three SNPs of cyp51A, referred to as cyp51A-3SNPs. Few studies have compared the distributions of cyp51A polymorphisms between different regions.
The aim of this study was to investigate the regional differences of cyp51A polymorphisms.
We compared the proportions of cyp51A polymorphisms in clinical and environmental strains isolated in various countries, and analysed the strains phylogenetically using short tandem repeats (STRs) and whole-genome sequence (WGS).
Among the Japanese strains, 15 out of 98 (15.3%) clinical strains and 8 out of 95 (8.4%) environmental strains had cyp51A polymorphisms. A mutation of cyp51A was the most prevalent polymorphism in both clinical (n = 14, 14.3%) and environmental strains (n = 3, 3.2%). Only one environmental strain harboured cyp51A-5SNPs, which was reported to be the most prevalent in Europe. For phylogenetic analyses using STRs and WGS, 183 and 134 strains, respectively, were employed. They showed that most of the strains with cyp51A clustered in the clades different from those of the strains with cyp51A-5SNPs and cyp51A-3SNPs as well as from those with TR /L98H mutations.
This study suggests that there are genetic differences between cyp51A polymorphisms of A. fumigatus in Japan and Europe.
cyp51A 基因突变是烟曲霉唑类耐药的主要机制，而唑类敏感株也携带 cyp51A 突变（多态性）。在欧洲发现的多态性主要由两种 cyp51A 突变组合组成，即 cyp51A 的五个单核苷酸多态性（SNP）的组合，称为 cyp51A-5SNPs，以及 cyp51A 的三个 SNP 的组合，称为 cyp51A-3SNPs。很少有研究比较不同地区 cyp51A 多态性的分布。
本研究旨在探讨 cyp51A 多态性的区域性差异。
我们比较了来自不同国家的临床和环境分离株中 cyp51A 多态性的比例，并使用短串联重复（STR）和全基因组序列（WGS）对菌株进行系统发育分析。
在日本株中，98 株临床株中有 15 株（15.3%）和 95 株环境株中有 8 株（8.4%）存在 cyp51A 多态性。cyp51A 突变是临床株（n=14，14.3%）和环境株（n=3，3.2%）中最常见的多态性。只有一株环境株携带 cyp51A-5SNPs，这是欧洲最常见的多态性。使用 STR 和 WGS 进行系统发育分析时，分别使用了 183 株和 134 株菌株。结果表明，大多数携带 cyp51A 的菌株聚类在与携带 cyp51A-5SNPs 和 cyp51A-3SNPs 以及 TR/L98H 突变的菌株不同的分支中。
本研究表明，日本和欧洲烟曲霉 cyp51A 多态性存在遗传差异。
