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寄生虫产生表型多样性,并影响 的耐药性和毒力。

Parasex Generates Phenotypic Diversity and Impacts Drug Resistance and Virulence in .

机构信息

Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912.

Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912

出版信息

Genetics. 2017 Nov;207(3):1195-1211. doi: 10.1534/genetics.117.300295. Epub 2017 Sep 14.

Abstract

is a diploid fungus that is a frequent cause of mucosal and systemic infections in humans. This species exhibits an unusual parasexual cycle in which mating produces tetraploid cells that undergo a nonmeiotic program of concerted chromosome loss to return to a diploid or aneuploid state. In this work, we used a multipronged approach to examine the capacity of parasex to generate diversity in First, we compared the phenotypic properties of 32 genotyped progeny and observed wide-ranging differences in fitness, filamentation, biofilm formation, and virulence. Strikingly, one parasexual isolate displayed increased virulence relative to parental strains using a model of infection, establishing that parasex has the potential to enhance pathogenic traits. Next, we examined parasexual progeny derived from homothallic, same-sex mating events, and reveal that parasex can generate diversity from identical parental strains. Finally, we generated pools of parasexual progeny and examined resistance of these pools to environmental stresses. Parasexual progeny were generally less fit than control strains across most test conditions, but showed an increased ability to grow in the presence of the antifungal drug fluconazole (FL). FL-resistant progeny were aneuploid isolates, often being diploid strains trisomic for both Chr3 and Chr6. Passaging of these aneuploid strains frequently led to loss of the supernumerary chromosomes and a concomitant decrease in drug resistance. These experiments establish that parasex generates extensive phenotypic diversity , and that this process has important consequences for both virulence and drug resistance in populations.

摘要

是一种二倍体真菌,常引起人类黏膜和全身感染。该物种表现出一种不寻常的准性生殖周期,在该周期中,交配产生四倍体细胞,这些细胞经历非减数分裂程序的协同染色体丢失,以恢复二倍体或非整倍体状态。在这项工作中,我们采用了多管齐下的方法来研究准性生殖在 中的多样性产生能力。首先,我们比较了 32 个基因分型后代的表型特性,观察到适应性、菌丝形成、生物膜形成和毒力等方面存在广泛差异。引人注目的是,一个准性分离株在感染模型中相对于亲本菌株表现出更高的毒力,这表明准性生殖有潜力增强致病特征。其次,我们检查了来自同型交配的准性后代,揭示了准性生殖可以从相同的亲本菌株中产生多样性。最后,我们生成了准性生殖后代的池,并检查了这些池对环境应激的抗性。准性生殖后代在大多数测试条件下的适应性通常低于对照菌株,但表现出在抗真菌药物氟康唑(FL)存在下生长的能力增强。FL 抗性后代是非整倍体分离株,通常是 Chr3 和 Chr6 都三体的二倍体菌株。这些非整倍体菌株的传代经常导致多余染色体的丢失,并伴随药物抗性的降低。这些实验确立了准性生殖产生广泛的表型多样性,并且该过程对 中的毒力和药物抗性具有重要影响。

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