The ability to appropriately respond to environmental conditions is critical for the survival of simple microbes and for development of complex multicellular organisms. Sensing and responding to a given environmental condition requires the integration of numerous signals through one or more signal transduction pathways. This leads to changes in gene expression, and potentially post-translational modifications, that favour growth in the given environment. In the fungus Candida albicans, an important opportunistic pathogen, environmental pH has profound effects on morphology and proper adaptation to extracellular pH is critical for pathogenesis. Here, we demonstrate that the Rim101/PacC pH-sensing pathway acts in parallel to Crz1, via calcineurin, to adapt to alkaline pH. We also show that the Rim101 pathway acts in parallel to Crz2, independent of calcineurin, to adapt to high lithium concentrations and to repress filamentation at acidic pH. Our studies also revealed a novel requirement for Crz1, Crz2 and calcineurin for growth at acidic pH. From these studies, we propose that the Crz1 homologue Crz2 is calcineurin-independent, but like Crz1, acts in parallel to promote specific Rim101-dependent processes. These results establish and begin to dissect the complex interactions between important signal transduction pathways in C. albicans, which are critical for virulence.

译文

对环境条件做出适当反应的能力对于简单微生物的生存和复杂多细胞生物的发育至关重要。感测和响应给定的环境条件需要通过一个或多个信号转导途径整合众多信号。这会导致基因表达的变化,以及潜在的翻译后修饰,从而有利于在给定环境中生长。在重要的机会性病原体白色念珠菌中,环境pH对形态有深远的影响,对细胞外pH的适当适应对发病机理至关重要。在这里,我们证明了Rim101/PacC pH感应途径通过钙调神经磷酸酶与Crz1平行作用,以适应碱性pH。我们还表明,Rim101途径与Crz2平行,独立于钙调神经磷酸酶,以适应高锂浓度并抑制酸性pH下的丝化。我们的研究还揭示了Crz1,Crz2和钙调神经磷酸酶在酸性pH下生长的新需求。从这些研究中,我们建议Crz1同源物Crz2不依赖钙调神经磷酸酶,但与Crz1一样,平行作用以促进特定的Rim101-dependent过程。这些结果建立并开始剖析白色念珠菌重要信号转导途径之间的复杂相互作用,这对毒力至关重要。

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