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Genetic diversity of clinical and environmental Mucorales isolates obtained from an investigation of mucormycosis cases among solid organ transplant recipients
Microbial Genomics ( IF 4.0 ) Pub Date : 2020-12-01 , DOI: 10.1099/mgen.0.000473
M Hong Nguyen 1, 2 , Drishti Kaul 3 , Carlene Muto 1, 2, 4 , Shaoji J Cheng 1 , R Alex Richter 3 , Vincent M Bruno 5 , Guojun Liu 1 , Sinem Beyhan 3 , Alexander J Sundermann 2, 6 , Stephanie Mounaud 7 , A William Pasculle 1, 2 , William C Nierman 7 , Eileen Driscoll 1 , Richard Cumbie 2 , Cornelius J Clancy 1 , Christopher L Dupont 3
Affiliation  

Mucormycoses are invasive infections by Rhizopus species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to Rhizopus microsporus (n=2), R. arrhizus (n=1) or Lichtheimia corymbifera (n=1), at a median 31.5 days (range: 13–34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 R. arrhizus, 19 R. delemar, six R. microsporus, two Lichtheimia species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine–cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of R. microsporus isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.

中文翻译:


通过对实体器官移植受者中毛霉菌病病例的调查获得的临床和环境毛霉目分离株的遗传多样性



毛霉菌病是根霉菌属和其他毛霉菌目的侵袭性感染。在 10 个月内,我们中心的 4 名实体器官移植 (SOT) 受者因小孢子根霉( n =2)、无根根霉菌( n =1) 或伞形李霉( n =1) 出现毛霉菌病,中位发病时间为 31.5 天(范围:13-34)入院后。我们对来自这些患者、5 名社区获得性毛霉菌病患者以及来自医院和地区的 72 株毛霉目分离株(45无根毛霉菌、19霉菌、6 株小孢子菌、2 种利赤霉属物种)进行了全基因组测序 (WGS)。环境。通过核心蛋白系统发育和整体基因组特征(包括基因组大小、鸟嘌呤-胞嘧啶百分比、共享蛋白家族和旁系同源物扩展)对分离株进行比较。患者分离株分为六个核心系统发育谱系(进化枝)。邻近医院的两名 SOT 接受者相隔 7 个月恢复的小孢子菌分离株的系统发育和基因组相似性表明存在潜在的共同源暴露。然而,来自其他患者和环境地点的分离株具有独特的基因组。许多通过核心系统发育无法区分的分离株通过一项或多项全球基因组比较是不同的。某些进化枝在整个研究期间被发现,而其他进化枝则是在特定时间点发现的。总之,毛霉菌病病例不可能与确定的环境来源有遗传联系。 全面的基因组分析消除了毛霉目分离株之间的错误关联,这些关联本来可以使用核心系统发育或不太广泛的基因组比较来分配。毛霉目的基因组多样性要求在流行病学调查期间对来自个体患者和环境场所的多个分离株进行全基因组测序。然而,对医院和周边社区的真菌种群进行详尽的监测可能是不可行的。
更新日期:2020-12-22
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