Comparative genomics of opportunistic Phialophora species involved in divergent disease types

Comparative genomics of opportunistic Phialophora species involved in divergent disease types
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涉及不同疾病类型的机会性瓶霉属物种的比较基因组学

DOI:
10.1111/myc.13244
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发表时间:
2021-01-26
期刊:
影响因子:
4.9
通讯作者:
Li, Ruoyu
Li, Ruoyu
中科院分区:
医学2区
文献类型:
--
作者:
Song, Yinggai;Menezes da Silva, Nickolas;Li, Ruoyu

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背景黑色机会菌疣状芽孢杆菌复合体可在正常和免疫功能低下的个体中引起不同的疾病类型,但在card9相关感染中表现明显过高。目的更好地了解机会性Phialophora物种的生态学和潜在致病性,揭示与CARD9免疫缺陷患者体内行为和遗传谱相关的最终遗传参数。方法对疣藻复合体6种26株进行基因组测序。采用多位点分析,所有环境和临床菌株均得到正确鉴定。我们比较了包括CARD9免疫缺陷在内的不同疾病类型的病原体基因组。结果26株紫孢菌的基因组大小在32 ~ 37mb之间,部分种间存在较大的基因组变异。美洲藜表现出最高程度的变异。疣状棘豆在CAZy酶上是可变的,而美洲棘豆在pks相关基因上是可变的。Phialophora,特别是疣状棘球蚴(P verrucosa)在card9相关免疫缺陷患者中较为常见。CARD9基因的不同突变似乎增加了不同物种群(念珠菌、皮肤真菌或黑真菌)感染的易感性。许多嗜铬菌病患者显示出一种未知的CARD9突变。CARD9感染患者普遍存在TNF - α损伤,而CBM患者总是IFN - γ损伤。结论基因组学调查显示,临床菌株和环境菌株的已知毒力因子无显著差异。无论是健康人还是card9受损的人,Phialophora复合物都有同样的机会引起感染。
Background Black opportunists Phialophora verrucosa complex species can cause different disease types in competent and in immunocompromised individuals, but are remarkably overrepresented in CARD9-related infections.Objectives To better understand the ecology and potential pathogenicity of opportunistic Phialophora species and reveal eventual genetic parameters associated with the behaviour in vivo and genetic profiles in patients with CARD9 immunodeficiency.Methods Genomes of 26 strains belonging to six species of the Phialophora verrucosa complex were sequenced. Using multilocus analysis, all environmental and clinical strains were identified correctly. We compared the genomes of agents from different disease types among each other including CARD9 immunodeficiency.Results We obtained genome sizes of the 26 Phialophora strains ranged between 32 and 37 MB. Some species showed considerable intraspecific genomic variation. P americana showed the highest degree of variability. P verrucosa was variable in CAZy enzymes, whereas P americana varied in PKS-related genes. Phialophora species, particularly P verrucosa, are relatively frequent in patients with CARD9-related immunodeficiency. Different mutations in the CARD9 gene seem to increase susceptibility for infection by different groups of species, that is either Candida, dermatophytes or black fungi. A number of patients with chromoblastomycosis revealed an as yet unknown CARD9 mutation. TNF alpha impairment was prevalent in patients with CARD9 infections, while CBM patients were invariably IFN gamma.Conclusions From genomic investigations, the known virulence factors between clinical and environmental strains did not reveal any significant difference. Phialophora complex has an equal chance to cause infection in humans, either healthy or CARD9-impaired.