Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, Iowa, USA.
Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, Iowa, USA
mSphere. 2020 Sep 23;5(5):e00918-20. doi: 10.1128/mSphere.00918-20.
, a pervasive opportunistic pathogen, undergoes a unique phenotypic transition from a "white" phenotype to an "opaque" phenotype. The switch to opaque impacts gene expression, cell morphology, wall structure, metabolism, biofilm formation, mating, virulence, and colonization of the skin and gastrointestinal (GI) tract. Although the regulation of switching is complex, a paradigm has evolved from a number of studies, in which, in its simplest form, the transcription factors Efg1 and Wor1 play central roles. When is upregulated under physiological conditions, it represses , an activator of white-to-opaque switching, and the cell expresses the white phenotype; when is downregulated, is derepressed and activates expression of the opaque phenotype. Deletion of either or supports this yin-yang model of regulation. Here, we demonstrate that this simple model is insufficient, since strains in which and are simultaneously deleted can still be induced to switch from white to opaque. Opaque cells of double mutants ( ) are enlarged and elongate, form an enlarged vacuole, upregulate under the control of an opaque-specific promoter, form opaque cell wall pimples, express the opaque phenotype in lower GI colonization, and, if homozygous, form conjugation tubes in response to pheromone and mate. These results can be explained if the basic and simplified model is expanded to include a -independent alternative opaque pathway repressed by The switch from white to opaque in was discovered 33 years ago, but it is still unclear how it is regulated. A regulatory paradigm has emerged in which two transacting factors, Efg1 and Wor1, play central roles, Efg1 as a repressor of , which encodes an activator of the transition to the opaque phenotype. However, we show here that if both and are deleted simultaneously, bona fide opaque cells can still be induced These results are not compatible with the simple paradigm, suggesting that an alternative opaque pathway (AOP) exists, which can activate expression of opaque and, like , is repressed by .
白色念珠菌是一种普遍存在的机会性病原体，它会经历从“白色”表型到“不透明”表型的独特表型转变。这种转变会影响基因表达、细胞形态、细胞壁结构、代谢、生物膜形成、交配、毒力以及皮肤和胃肠道（GI）的定植。尽管开关的调控非常复杂，但已经从许多研究中发展出了一个范例，在这个范例中，转录因子 Efg1 和 Wor1 发挥着核心作用。当 在生理条件下被上调时，它会抑制 ，而 是白色到不透明转变的激活剂，细胞会表达白色表型；当 被下调时， 会被解除抑制并激活不透明表型的表达。缺失 或 都支持这种阴阳调控模式。在这里，我们证明这个简单的模型是不够的，因为同时缺失 或 的菌株仍然可以被诱导从白色转变为不透明。双突变体（ ）的不透明细胞会增大和伸长，形成一个增大的液泡，在一个不透明特异性启动子的控制下上调 ，形成不透明细胞壁粉刺，在下胃肠道定植中表现出不透明表型，如果 是纯合的，会响应信息素形成交配管并交配。如果将基本和简化的模型扩展到包括 独立的、受 抑制的替代不透明途径，那么这些结果就可以得到解释。白色念珠菌从白色到不透明的转变是在 33 年前发现的，但它的调控机制仍不清楚。一个调控范例已经出现，其中两个反式作用因子 Efg1 和 Wor1 发挥核心作用，Efg1 作为 编码的抑制剂， 编码的是向不透明表型转变的激活剂。然而，我们在这里表明，如果同时缺失 或 ，仍然可以诱导真正的不透明细胞。这些结果与简单的范例不一致，表明存在替代不透明途径（AOP），它可以激活不透明的表达，并且像 一样，受到 的抑制。
