Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.
PLoS One. 2012;7(6):e39624. doi: 10.1371/journal.pone.0039624. Epub 2012 Jun 27.
The human opportunistic pathogen Candida albicans undergoes a reversible morphological transition between the yeast and hyphal states in response to a variety of signals. One such environmental trigger is growth within a semisolid matrix such as agar medium. This growth condition is of interest because it may mimic the growth of C. albicans in contact with host tissue during infection. During growth within a semisolid matrix, hyphal growth is positively regulated by the transcriptional regulator Czf1p and negatively by a second key transcriptional regulator, Efg1p. Genetic studies indicate that Czf1p, a member of the zinc-cluster family of transcriptional regulators, exerts its function by opposing the inhibitory influence of Efg1p on matrix-induced filamentous growth. We examined the importance of the two known activities of Czf1p, DNA-binding and interaction with Efg1p. We found that the two activities were separable by mutation allowing us to demonstrate that the DNA-binding activity of Czf1p was essential for its role as a positive regulator of morphogenesis. Surprisingly, however, interactions with Efg1p appeared to be largely dispensable. Our studies provide the first evidence of a key role for the DNA-binding activity of Czf1p in the morphological yeast-to-hyphal transition triggered by matrix-embedded growth.
人类机会致病菌白色念珠菌在响应各种信号时,会在酵母和菌丝两种形态之间发生可逆的形态转变。其中一种环境触发因素是在半固体基质(如琼脂培养基)中生长。这种生长条件很有趣,因为它可能模拟了白色念珠菌在感染过程中与宿主组织接触时的生长方式。在半固体基质中生长时,菌丝生长受到转录调节因子 Czf1p 的正向调控,而受到另一个关键转录调节因子 Efg1p 的负向调控。遗传研究表明,锌指家族转录调节因子的成员 Czf1p 通过拮抗 Efg1p 对基质诱导丝状生长的抑制作用来发挥其功能。我们研究了 Czf1p 的两种已知活性(DNA 结合和与 Efg1p 的相互作用)的重要性。我们发现,通过突变可以将这两种活性分离,这使我们能够证明 Czf1p 的 DNA 结合活性对于其作为形态发生正向调节剂的作用至关重要。然而,令人惊讶的是,与 Efg1p 的相互作用似乎在很大程度上是可有可无的。我们的研究首次提供了证据,证明 Czf1p 的 DNA 结合活性在基质嵌入生长触发的形态酵母到菌丝的转变中起着关键作用。