Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain.
Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain.
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由于更好的代谢适应性导致的快速增殖导致毒力缺陷型白色念珠菌菌株的完全毒力。
DOI：
10.1038/s41467-021-24095-8
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发表时间：
2021-06-23
影响因子：
16.6
通讯作者：
Jacobsen ID
中科院分区：
文献类型：
--
作者：
Dunker C;Polke M;Schulze-Richter B;Schubert K;Rudolphi S;Gressler AE;Pawlik T;Prada Salcedo JP;Niemiec MJ;Slesiona-Künzel S;Swidergall M;Martin R;Dandekar T;Jacobsen ID
真菌病原体白色念珠菌经历酵母到菌丝的转变的能力被认为是一个关键的毒力因素，因为细丝介导组织损伤。在这里，我们表明，在缺乏丝状物的菌株中，毒力不一定会降低，结果取决于所使用的感染模型。我们通过缺失或抑制EED1(已知是维持菌丝生长所必需的)来产生细丝缺陷菌株。与之前的研究一致，该菌株在体外和小鼠腹膜感染模型中对上皮细胞和巨噬细胞的破坏作用减弱。然而，在全身感染的小鼠模型中，当小鼠受到中等感染剂量的攻击时，该菌株的毒力与野生型相同，而当使用低感染剂量时，其毒力甚至更强。保留的毒力与酵母的快速增殖有关，这可能是代谢适应和适应性提高的结果，导致器官真菌负荷较高。对体外和体内的细胞因子反应以及免疫抑制小鼠的全身感染的分析表明，免疫病理上的差异在一定程度上有助于保持丝蛋白缺陷突变体的毒力。我们的发现挑战了长期以来的假设，即菌丝在白念珠菌系统性念珠菌病的发病机制中是必不可少的。真菌病原体白色念珠菌从酵母到菌丝转化的能力被认为是一个关键的毒力因素。这里，Dunker等人。结果表明，在腹膜感染的小鼠模型中，细丝缺陷菌株会减弱，但在系统性念珠菌病的小鼠模型中仍保持毒力。
The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans. The ability of the fungal pathogen Candida albicans to undergo yeast-to-hypha transition is believed to be a key virulence factor. Here, Dunker et al. show that a filament-deficient strain is attenuated in a mouse model of intraperitoneal infection, but remains virulent in a mouse model of systemic candidiasis.
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影响因子：
6.7
作者：
Childers DS;Raziunaite I;Mol Avelar G;Mackie J;Budge S;Stead D;Gow NA;Lenardon MD;Ballou ER;MacCallum DM;Brown AJ
通讯作者：
Brown AJ
影响因子：
15.9
作者：
Brown, Alistair J. P.;Brown, Gordon D.;Netea, Mihai G.;Gow, Neil A. R.
通讯作者：
Gow, Neil A. R.
影响因子：
6.7
作者：
Böhm L;Torsin S;Tint SH;Eckstein MT;Ludwig T;Pérez JC
通讯作者：
Pérez JC
影响因子：
28.3
作者：
Ballou ER;Avelar GM;Childers DS;Mackie J;Bain JM;Wagener J;Kastora SL;Panea MD;Hardison SE;Walker LA;Erwig LP;Munro CA;Gow NA;Brown GD;MacCallum DM;Brown AJ
通讯作者：
Brown AJ
影响因子：
4.9
作者：
Bowman, JC;Abruzzo, GK;Douglas, CM
通讯作者：
Douglas, CM