Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1
Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1
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DOI：
10.1128/ec.5.1.103-111.2006
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Mühlschlegel, FA
中科院分区：
文献类型：
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作者：
Mogensen, EG;Janbon, G;Mühlschlegel, FA
新型隐球菌是人类的一种真菌病原体，在免疫功能低下的患者中引起致命的脑膜炎。它的毒力主要取决于其细胞壁周围的多糖胶囊的形成。在其一生中，新形态C.要面对并应对二氧化碳浓度的剧烈变化；从其自然栖息地（CO2浓度为0.033%）到感染宿主（CO2浓度为5%）的转变所引发的一个重要形态变化是诱导荚膜生物合成。在细胞中，二氧化碳在碳酸酐酶加速的自发反应中水合成碳酸氢盐。在这里，我们发现新生C.含有两个β -类碳酸酐酶，Can1和Can2。我们进一步证明，CAN2（但不是CAN）在自然环境中大量表达，并且对C. neoformans在二氧化碳浓度有限的环境中生长至关重要。结构研究表明Can2在溶液中形成同型二聚体。我们的数据显示Can2是主要的碳酸酐酶，并提示碳酸氢盐在新生C.生长过程中的生理作用。碳酸氢盐直接激活新形态c的Cac1腺苷酸环化酶所需的胶囊合成。我们发现这种特定的激活在生理pH值下是最佳的。
Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO2) to infected hosts (5% CO2) is the induction of capsule biosynthesis. In cells, CO2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two beta-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN], is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and suggest a physiological role for bicarbonate during C. neoformans growth. Bicarbonate directly activates the C. neoformans Cac1 adenylyl cyclase required for capsule synthesis. We show that this specific activation is optimal at physiological pH.