Molecular Microbiology and Immunology Department, Brown University, Providence, RI 02912, USA.
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2510-5. doi: 10.1073/pnas.1017234108. Epub 2011 Jan 24.
The opportunistic pathogen Candida albicans undergoes a parasexual mating cycle in which cells must switch from the conventional "white" form to the alternative "opaque" form to become mating competent. Pheromones secreted by opaque cells induce the formation of polarized mating projections and result in cell-cell conjugation. In contrast, white cells are unable to undergo mating, but can still respond to pheromone by expression of adhesion genes that promote biofilm formation. In this study, we have analyzed the dual ability of pheromones to activate mating by opaque cells and biofilm formation by white cells. We first show that there is considerable plasticity in interactions between the α pheromone and its receptor, Ste2, by analysis of analogs of the α pheromone. Significantly, substituted forms of α pheromone can induce a response in opaque cells and this is sufficient to drive same-sex a-a cell fusion and homothallic mating. In addition, pheromone analogs were able to induce adhesion and biofilm formation in white cells of C. albicans. Because of the observed plasticity in pheromone signaling, we subsequently tested putative pheromones from multiple Candida species and identified nonnative ligands that can induce self-mating and biofilm responses in C. albicans. Our findings demonstrate that environmental signals can initiate C. albicans parasexual reproduction and biofilm formation, and highlight the role of the pheromone-signaling apparatus in mediating these functions.
机会性病原体白色念珠菌经历了一种有性生殖的交配周期，在此过程中，细胞必须从常规的“白色”形式转变为替代的“不透明”形式，才能具有交配能力。不透明细胞分泌的信息素诱导极化交配突起的形成，并导致细胞-细胞融合。相比之下，白色细胞无法进行交配，但仍能通过表达促进生物膜形成的粘附基因对信息素做出反应。在这项研究中，我们分析了信息素对不透明细胞激活交配和白色细胞形成生物膜的双重能力。我们首先通过对α信息素类似物的分析，表明α信息素与其受体 Ste2 之间的相互作用具有相当大的可塑性。值得注意的是，α信息素的取代形式可以诱导不透明细胞的反应，这足以驱动同型 a-a 细胞融合和同种交配。此外，信息素类似物能够诱导白色念珠菌白色细胞的粘附和生物膜形成。由于观察到信息素信号的可塑性，我们随后测试了来自多种念珠菌物种的假定信息素，并鉴定出能够在白色念珠菌中诱导自我交配和生物膜反应的非天然配体。我们的研究结果表明，环境信号可以启动白色念珠菌的有性生殖和生物膜形成，并强调了信息素信号装置在介导这些功能中的作用。
