Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis
Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis
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DOI：
10.1093/femsyr/fow011
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发表时间：
2016-03-01
影响因子：
3.2
通讯作者：
Saville, Stephen P.
中科院分区：
文献类型：
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作者：
Cleary, Ian A.;Reinhard, Sara M.;Saville, Stephen P.
白色念珠菌是一种机会性真菌病原体，对人类健康的威胁日益普遍。白色念珠菌以几种形态生长，锁定在酵母或丝状形态中的突变菌株在播散性白念珠菌病小鼠模型中的毒力有所减弱。因此，改变形状的能力对毒力很重要。转录抑制因子Nrg1p和Tup1p是白念珠菌形态正常调节所必需的。缺乏NRG1或Tup1的菌株在酵母生长条件下呈结构性假菌丝，在播散模型中显示出减弱的毒力。为了剖析菌丝和假菌丝在感染过程中的相对重要性，我们使用了可以通过控制NRG1或Tup1的表达来外部操纵形态转换的菌株。值得注意的是，菌丝形态的接种物保持了致病能力。虽然通过耗尽Tup1诱导假菌丝形态确实导致毒力减弱，但这并不是由于逃避血流的能力缺陷所致。相反，我们观察到伪菌丝细胞从组织中清除的效率比菌丝(毒力)或酵母形式(无毒)细胞高得多，这表明不同形态的白色念珠菌在感染期间与宿主细胞有不同的相互作用。
The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health. Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we used strains in which the morphological transition could be externally manipulated through controlled expression of NRG1 or TUP1. Remarkably, hyphal form inocula retain the capacity to cause disease. Whilst induction of a pseudohyphal morphology through depletion of TUP1 did result in attenuated virulence, this was not due to a defect in the ability to escape the bloodstream. Instead, we observed that pseudohyphal cells are cleared from tissues much more efficiently than either hyphal (virulent) or yeast form (avirulent) cells, indicating that different C. albicans morphologies have distinct interactions with host cells during an infection.