Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21158-63. doi: 10.1073/pnas.1112076109. Epub 2011 Dec 8.
Sexual reproduction can promote genetic diversity in eukaryotes, and yet many pathogenic fungi have been labeled as obligate asexual species. It is becoming increasingly clear, however, that cryptic sexual programs may exist in some species, and that efficient mating requires the necessary developmental switch to be triggered. In this study we investigate Candida tropicalis, an important human fungal pathogen that has been reported to be asexual. Significantly, we demonstrate that C. tropicalis uses a phenotypic switch to regulate a cryptic program of sexual mating. Thus, diploid a and α cells must undergo a developmental transition to the mating-competent form, and only then does efficient cell-cell conjugation take place resulting in the formation of stable a/α tetraploids. We show that both the phenotypic switch and sexual mating depend on the conserved transcriptional regulator Wor1, which is regulated by temperature in other fungal species. In contrast, C. tropicalis mating occurs efficiently at both 25 °C and 37 °C, suggesting that it could occur in the mammalian host and have direct consequences for the outcome of an infection. Transcriptional profiling further reveals that ≈ 400 genes are differentially expressed between the two phenotypic states, including the regulatory factor Wor1. Taken together, our results demonstrate that C. tropicalis has a unique sexual program, and that entry to this program is controlled via a Wor1-mediated, metastable switch. These observations have direct implications for the regulation and evolution of cryptic sexual programs in related fungal pathogens.
有性繁殖可以促进真核生物的遗传多样性，但许多致病性真菌被标记为专性无性物种。然而，越来越明显的是，一些物种可能存在隐性的有性生殖程序，而有效的交配需要触发必要的发育开关。在这项研究中，我们研究了热带假丝酵母（Candida tropicalis），一种重要的人类真菌病原体，据报道它是无性的。重要的是，我们证明了 C. tropicalis 使用表型转换来调节隐性的有性交配程序。因此，二倍体 a 和 α 细胞必须经历向有性交配能力的形式的发育转变，只有这样才能有效地进行细胞间融合，形成稳定的 a/α 四倍体。我们表明，表型转换和有性交配都依赖于保守的转录调节因子 Wor1，在其他真菌物种中，Wor1 受温度调节。相比之下，C. tropicalis 在 25°C 和 37°C 都能有效地进行交配，这表明它可能在哺乳动物宿主中发生，并对感染的结果产生直接影响。转录谱分析进一步显示，在两种表型状态之间有 ≈ 400 个基因差异表达，包括调节因子 Wor1。总之，我们的结果表明，C. tropicalis 有一个独特的有性生殖程序，而进入这个程序是通过 Wor1 介导的、亚稳态开关来控制的。这些观察结果对相关真菌病原体中隐性有性生殖程序的调节和进化具有直接影响。
