Environmental induction of white-opaque switching in Candida albicans.

Environmental induction of white-opaque switching in Candida albicans.
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DOI:
10.1371/journal.ppat.1000089
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发表时间:
2008-06-13
期刊:
影响因子:
6.7
通讯作者:
Morschhäuser J
Morschhäuser J
中科院分区:
医学1区
文献类型:
--
作者:
Ramírez-Zavala B;Reuss O;Park YN;Ohlsen K;Morschhäuser J

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在交配型基因座(MTL α或MTLα)处纯合的白色念珠菌菌株可以以低频率自发地从正常酵母细胞形态(白色)转变为细长细胞类型(不透明),这是真菌的交配能力形式。在这两种细胞类型之间可逆转换的能力也有助于C的致病性。白色念珠菌,因为白色和不透明细胞不同地适应特定的宿主小生境。我们发现,在WO-1菌株中,基因组发生了改变,但在其他测试菌株中没有,从白色到不透明相的转换也可以由环境条件诱导。在厌氧条件下短暂孵育白色细胞,使细胞程序化,从而转换为不透明相。白色-不透明转换的厌氧诱导由转录因子CZF 1控制,CZF 1在杂合MTL a/α细胞中调节嵌入的缺氧条件下的丝状生长。有趣的是,菌株WO-1的白色细胞通过小鼠肠(细胞可能暴露于厌氧条件的宿主生态位)的通道导致切换到不透明相的频率大幅增加。这些结果表明,白色不透明转换不仅是一个自发的过程,但结合基因组改变,也可以由环境信号诱导,这表明转换和交配的C。白色念珠菌可以在其人类宿主内的适当小生境中以高效率发生。条件致病真菌白色念珠菌的一些菌株可以可逆地从正常的酵母形态(白色)转变为称为不透明的细长细胞类型,这是C.白色念珠菌C.白色念珠菌菌株首先必须在交配型基因座处变成纯合的,以便能够转换到通常毒性较小的不透明相。由于白色不透明转换仅以低频率自发发生,因此不同菌株和交配类型的不透明细胞的相遇预计是极其罕见的事件,并且在自然界中菌株之间很少发生重组。我们发现,基因组的改变可能使白色不透明转换环境诱导在某些C。白色念珠菌菌株。在厌氧条件下瞬时孵育这样的菌株诱导质量转换的白色细胞的不透明相,这种诱导是由转录因子Czf 1 p介导的。最引人注目的是,白色细胞通过哺乳动物的肠道,在这种环境中细胞遇到厌氧条件,也刺激了向不透明相的转变。因此,部分C.白念珠菌可被诱导以响应于环境信号而切换到具有交配能力的不透明相,从而使它们有机会在适当的宿主小生境中进行有效的遗传交换。
Candida albicans strains that are homozygous at the mating type locus (MTL a or MTLα) can spontaneously switch at a low frequency from the normal yeast cell morphology (white) to an elongated cell type (opaque), which is the mating-competent form of the fungus. The ability to switch reversibly between these two cell types also contributes to the pathogenicity of C. albicans, as white and opaque cells are differently adapted to specific host niches. We found that in strain WO-1, a strain in which genomic alterations have occurred, but not in other tested strains, switching from the white to the opaque phase can also be induced by environmental conditions. Transient incubation of white cells under anaerobic conditions programmed the cells to switch en masse to the opaque phase. The anaerobic induction of white–opaque switching was controlled by the transcription factor CZF1, which in heterozygous MTL a/α cells regulates filamentous growth under embedded, hypoxic conditions. Intriguingly, passage of white cells of strain WO-1 through the mouse intestine, a host niche in which the cells are likely to be exposed to anaerobic conditions, resulted in a strongly increased frequency of switching to the opaque phase. These results demonstrate that white–opaque switching is not only a spontaneous process but, in combination with genomic alterations, can also be induced by environmental signals, suggesting that switching and mating of C. albicans may occur with high efficiency in appropriate niches within its human host. Some strains of the opportunistic fungal pathogen Candida albicans can reversibly switch from the normal yeast morphology (white) to an elongated cell type termed opaque, which is the mating-competent form of C. albicans. C. albicans strains first have to become homozygous at the mating type locus to be able to switch to the usually less virulent opaque phase. As white–opaque switching occurs spontaneously only at a low frequency, the encounter of opaque cells of different strains and mating types is expected to be an extremely rare event and little recombination between strains occurs in nature. We found that genomic alterations may render white–opaque switching environmentally inducible in certain C. albicans strains. A transient incubation of such a strain under anaerobic conditions induced mass switching of white cells to the opaque phase, and this induction was mediated by the transcription factor Czf1p. Most strikingly, passage of white cells through the mammalian intestine, an environment in which the cells encounter anaerobic conditions, also stimulated switching to the opaque phase. Therefore, some strains of C. albicans may be induced to switch to the mating-competent opaque phase in response to environmental signals, giving them an opportunity for efficient genetic exchange in appropriate host niches.
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