Institute for Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany.
Microbiol Spectr. 2021 Dec 22;9(3):e0121421. doi: 10.1128/Spectrum.01214-21. Epub 2021 Nov 17.
In Aspergillus fumigatus, the repetitive region of the gene is one of the most frequently used loci for intraspecies typing of this human pathogenic mold. Using PCR amplification and Sanger sequencing of only a single marker, typing is readily available to most laboratories and highly reproducible. Here, I evaluate the usefulness of the marker for resistance detection and epidemiologic stratification among A. fumigatus isolates. After resolving nomenclature conflicts from published studies and adding novel types, the number of known types now adds up to 38. Their distribution mostly correlates with A. fumigatus population structure, and they are also meaningful for narrowly defined cases of azole resistance phenotypes. Isolates carrying the pandemic resistance allele TR/L98H show signs of interclade crossing of strains with t02 or t04A, into the t11 clade. Furthermore, absolute differences in voriconazole MIC values between t02/t04B versus t11 TR/L98H isolates indicate that the genetic background of resistance mutations may have a pivotal role in cross-resistance phenotypes and, thus, clinical outcome and environmental selection. Despite the general genetic similarity of isolates with identical types, outcrossing into other clades is also observed. The type alone, therefore, does not sufficiently discriminate genetic clades to be used as the sole marker in epidemiologic studies. Aspergillus fumigatus is a ubiquitously distributed saprophytic mold and a leading cause of invasive aspergillosis in human hosts. Pandemic azole-resistant strains have emerged on a global scale, which are thought to be propagated through use of azole-based fungicides in agriculture. To perform epidemiologic studies, genetic typing of large cohorts is key. Here, I evaluate the usefulness of the frequently used marker for resistance detection and epidemiologic stratification among A. fumigatus isolates. The phylogenetic distribution of types mostly correlates with A. fumigatus population structure and is also meaningful for narrowly defined cases of azole resistance phenotypes. Nevertheless, outcrossing of into other clades is also observed. The type alone, therefore, does not sufficiently discriminate genetic clades and should not be used as the sole marker in epidemiologic studies.
在烟曲霉中，基因的重复区域是该人类致病性霉菌种内分型最常用的基因座之一。使用仅单个标记物的 PCR 扩增和 Sanger 测序，大多数实验室都可以轻松进行分型，且具有高度可重复性。在这里，我评估了 标记物在烟曲霉分离株中的耐药性检测和流行病学分层中的有用性。在解决了来自已发表研究的命名冲突并添加了新的类型后，现在已知的类型数增加到 38 个。它们的分布主要与烟曲霉种群结构相关，对于狭义定义的唑类耐药表型也具有意义。携带流行耐药等位基因 TR/L98H 的分离株显示出菌株与 t02 或 t04A 之间的跨群交叉的迹象，进入 t11 群。此外，t02/t04B 与 t11 TR/L98H 分离株之间伏立康唑 MIC 值的绝对差异表明，耐药突变的遗传背景可能在交叉耐药表型以及临床结果和环境选择中发挥关键作用。尽管具有相同 类型的分离株具有普遍的遗传相似性，但也观察到与其他群的杂交。因此，仅 类型本身不足以区分遗传群，不能用作流行病学研究中的唯一标记物。
烟曲霉是一种广泛分布的腐生真菌，是人类宿主侵袭性曲霉病的主要原因。全球范围内出现了流行的唑类耐药菌株，这些菌株被认为是通过农业中使用唑类杀菌剂而传播的。为了进行流行病学研究，对大型队列进行基因分型是关键。在这里，我评估了常用的 标记物在烟曲霉分离株中的耐药性检测和流行病学分层中的有用性。 类型的系统发育分布主要与烟曲霉种群结构相关，对于狭义定义的唑类耐药表型也具有意义。然而，也观察到 与其他群的杂交。因此，仅 类型本身不足以区分遗传群，不应在流行病学研究中用作唯一标记物。
