Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets.
Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets.
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DOI：
10.1093/genetics/iyac031
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发表时间：
2022-05-05
期刊：
影响因子：
3.3
通讯作者：
Farrer, Rhys A.
中科院分区：
文献类型：
--
作者：
Helmstetter, Nicolas;Chybowska, Aleksandra D.;Delaney, Christopher;Dantas, Alessandra Da Silva;Gifford, Hugh;Wacker, Theresa;Munro, Carol;Warris, Adilia;Jones, Brian;Cuomo, Christina A.;Wilson, Duncan;Ramage, Gordon;Farrer, Rhys A.
关键词：
光滑念珠菌是全球成人患者全身性念珠菌病的第二常见病因。对苏格兰 8 家医院的 68 个分离株以及全球 83 个分离株进行的基因组分析揭示了光滑念珠菌群体遗传学和进化的见解。来自苏格兰各地的光滑 C. glabrata 临床分离株具有高度遗传多样性，包括之前在全球不同地点发现的至少 19 种独立序列类型，以及 1 种新发现的序列类型。几种序列类型有祖先重组的证据，表明不同地理区域之间的传播与新进化枝中出现的遗传交换同时发生。三个分离株缺失 MATα1，可能代表第二种交配类型。在每种序列类型中都鉴定出正选择的特征，包括上皮粘附素的富集，被认为有助于真菌粘附素对人上皮细胞的粘附。在专利中，从 7 组复发性念珠菌病病例中鉴定出微进化，揭示了细胞表面蛋白中非同义和移码插入缺失的富集。患者体内的微进化也影响上皮粘附素基因，以及一些与耐药性相关的基因，包括麦角甾醇合成基因ERG4和棘白菌素靶点FKS1/2，后者与氟康唑最低抑菌浓度的显着下降同时发生。除了核基因组多样性之外，光滑念珠菌线粒体基因组也特别多样化，所有非参考 ST15 分离株中的保守序列和保守的蛋白质编码基因均减少。总之，这项研究强调了光滑念珠菌种群内可能影响毒力和耐药性的遗传多样性，以及产生这种多样性的两个主要机制：微进化和遗传交换/重组。
Candida glabrata is the second most common etiological cause of worldwide systemic candidiasis in adult patients. Genome analysis of 68 isolates from 8 hospitals across Scotland, together with 83 global isolates, revealed insights into the population genetics and evolution of C. glabrata. Clinical isolates of C. glabrata from across Scotland are highly genetically diverse, including at least 19 separate sequence types that have been recovered previously in globally diverse locations, and 1 newly discovered sequence type. Several sequence types had evidence for ancestral recombination, suggesting transmission between distinct geographical regions has coincided with genetic exchange arising in new clades. Three isolates were missing MATα1, potentially representing a second mating type. Signatures of positive selection were identified in every sequence type including enrichment for epithelial adhesins thought to facilitate fungal adhesin to human epithelial cells. In patent microevolution was identified from 7 sets of recurrent cases of candidiasis, revealing an enrichment for nonsynonymous and frameshift indels in cell surface proteins. Microevolution within patients also affected epithelial adhesins genes, and several genes involved in drug resistance including the ergosterol synthesis gene ERG4 and the echinocandin target FKS1/2, the latter coinciding with a marked drop in fluconazole minimum inhibitory concentration. In addition to nuclear genome diversity, the C. glabrata mitochondrial genome was particularly diverse, with reduced conserved sequence and conserved protein-encoding genes in all nonreference ST15 isolates. Together, this study highlights the genetic diversity within the C. glabrata population that may impact virulence and drug resistance, and 2 major mechanisms generating this diversity: microevolution and genetic exchange/recombination.
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影响因子：
3.4
作者：
Brunke S;Hube B
通讯作者：
Hube B
DOI：
10.1073/pnas.0304170101
发表时间：
2004-02-10
影响因子：
11.1
作者：
Butler, G;Kenny, C;Wolfe, KH
通讯作者：
Wolfe, KH
影响因子：
6.4
作者：
Arora P;Singh P;Wang Y;Yadav A;Pawar K;Singh A;Padmavati G;Xu J;Chowdhary A
通讯作者：
Chowdhary A
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DOI：
10.1016/j.cub.2017.11.027
发表时间：
2018-01-08
期刊：
Current biology : CB
影响因子：
--
作者：
Carreté L;Ksiezopolska E;Pegueroles C;Gómez-Molero E;Saus E;Iraola-Guzmán S;Loska D;Bader O;Fairhead C;Gabaldón T
通讯作者：
Gabaldón T
DOI：
10.1046/j.1471-8278.2000.00014.x
发表时间：
2001-03-01
期刊：
MOLECULAR ECOLOGY NOTES
影响因子：
--
作者：
Agapow, PM;Burt, A
通讯作者：
Burt, A