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采用全基因组和 IGS1 测序对聚集性新型隐球菌进行流行病学调查。

Epidemiological investigation for grouped cases of Trichosporon asahii using whole genome and IGS1 sequencing.

机构信息

Molecular Mycology Unit, UMR2000, Institut Pasteur, CNRS, National Reference Center for Invasive Mycoses & Antifungals, Paris, France.

Center of Bioinformatics for Biology, Institut Pasteur, Paris, France.

出版信息

Mycoses. 2020 Sep;63(9):942-951. doi: 10.1111/myc.13126. Epub 2020 Jul 1.

DOI:10.1111/myc.13126
PMID:32506754
Abstract

BACKGROUND

Trichosporonosis is a rare invasive infection in humans mainly due to Trichosporon asahii, and especially recovered from patients having haematological malignancy. Since 2012, IGS1 region sequencing is used as a genotyping method to distinguish isolates, with high frequency of one haplotype worldwide and a geographic specificity for some haplotypes.

OBJECTIVES

We compared the IGS1 genotyping method and whole genome sequencing (WGS) to study the relationship between clinical isolates involved in two grouped cases in France.

METHODS

IGS1 sequencing and antifungal susceptibility testing were performed for 54 clinical isolates. Clinical data for 28 isolates included in surveillance programs were analysed. Whole genome was sequenced for 32 clinical isolates and the type strain.

RESULTS

All isolates were intrinsically resistant to flucytosine, while voriconazole had the most potent in vitro activity. The majority of the isolates was recovered from patients with haematological malignancies (42.86%), with a high proportion of children (<15 yrs-old, 32.14%) and a high mortality rate at three months (46.15%). Based on the WGS analysis, isolates exhibiting IGS1 haplotype 1, 3 and 7 belonged to different clades. Five isolates recovered during the first grouped cases had the same IGS1 haplotype and shared 99% of SNPs similarity. For the second grouped cases, four isolates had 98.7% of SNPs similarity while the isolate recovered 4 years earlier was totally unlinked.

CONCLUSIONS

We confirmed the usefulness of IGS1 sequencing for grouped cases infection of T. asahii. We underlined its limitation for the study of population structure and the utility of WGS analysis for the study of epidemiologically unrelated isolates.

摘要

背景

毛孢子菌病是一种罕见的人类侵袭性感染,主要由 Trichosporon asahii 引起,尤其多见于血液恶性肿瘤患者。自 2012 年以来,IGS1 区测序被用作一种基因分型方法来区分分离株,在全球范围内具有一种单倍型的高频率,并且某些单倍型具有地理特异性。

目的

我们比较了 IGS1 基因分型方法和全基因组测序(WGS),以研究法国两组病例中涉及的临床分离株之间的关系。

方法

对 54 株临床分离株进行 IGS1 测序和抗真菌药敏试验。分析了纳入监测计划的 28 株临床分离株的临床数据。对 32 株临床分离株和参考株进行了全基因组测序。

结果

所有分离株均对氟胞嘧啶固有耐药,而伏立康唑具有最强的体外活性。大多数分离株来自血液恶性肿瘤患者(42.86%),儿童比例较高(<15 岁,32.14%),三个月死亡率较高(46.15%)。基于 WGS 分析,表现出 IGS1 单倍型 1、3 和 7 的分离株属于不同的分支。在第一组病例中分离到的五个分离株具有相同的 IGS1 单倍型,具有 99%的 SNP 相似性。对于第二组病例,四个分离株具有 98.7%的 SNP 相似性,而四年前分离到的分离株完全没有关联。

结论

我们证实了 IGS1 测序在 T. asahii 感染聚集病例中的有用性。我们强调了它在研究种群结构方面的局限性,以及 WGS 分析在研究流行病学上无关的分离株方面的实用性。

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