二氧化碳（CO2）不僅是植物光合作用的重要底物和細(xì)胞呼吸代謝的終產(chǎn)物,，也是一種重要的信號(hào)分子,，參與多種生物過(guò)程的調(diào)節(jié)。比如,，CO2是吸血性雌蚊尋找合適目標(biāo)的主要信號(hào)分子,，高濃度CO2能促進(jìn)動(dòng)物生殖細(xì)胞的成熟和游動(dòng)，甚至影響小型動(dòng)物（如果蠅和線(xiàn)蟲(chóng)）的壽命,。白色念珠菌既是人體重要的病原真菌,，也是健康人群體內(nèi)常見(jiàn)的共生菌。人體內(nèi)CO2濃度遠(yuǎn)遠(yuǎn)高于空氣中CO2濃度,，研究表明,，CO2在病原真菌白色念珠菌形態(tài)轉(zhuǎn)換和感染宿主過(guò)程中起重要的調(diào)控作用。高濃度CO2促進(jìn)菌絲生長(zhǎng)和灰菌（opaque）形成,，從而促進(jìn)白色念珠菌在體內(nèi)定植,。這種應(yīng)答作用是該菌與宿主相互作用及其長(zhǎng)期適應(yīng)性進(jìn)化的結(jié)果。盡管CO2在生物進(jìn)化和細(xì)胞生命活動(dòng)中起非常重要的作用,，目前對(duì)于CO2感應(yīng)的分子機(jī)制的了解還非常有限,。
最近，中科院微生物所真菌學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室黃廣華課題組研究發(fā)現(xiàn)轉(zhuǎn)錄因子Flo8在白色念珠菌感應(yīng)CO2過(guò)程中起關(guān)鍵的調(diào)控作用,。Flo 8含有一個(gè)真核生物中保守的LisH結(jié)構(gòu)域,，不僅調(diào)節(jié)CO2誘導(dǎo)的白色念珠菌“酵母-菌絲形態(tài)”轉(zhuǎn)換，也控制了“白菌-灰菌”之間的轉(zhuǎn)換,。該研究首次發(fā)現(xiàn)Flo8對(duì)于CO2誘導(dǎo)的菌絲生長(zhǎng)和灰菌形成都是必需的,。過(guò)表達(dá)FLO8基因則增強(qiáng)了白色念珠菌細(xì)胞感應(yīng)CO2的敏感性。進(jìn)一步研究證明,，白念株菌中兩條信號(hào)途徑參與了CO2感應(yīng),，即保守的cAMP/PKA通路和另一條未知途徑。這兩條通路最終匯合于轉(zhuǎn)錄因子Flo8,。Flo8再通過(guò)轉(zhuǎn)錄因子Efg1和細(xì)胞周期調(diào)控因子Hgc1等下游分子調(diào)控菌絲生長(zhǎng),；通過(guò)轉(zhuǎn)錄因子Wor1和Wor2調(diào)控“白菌-灰菌”形態(tài)的轉(zhuǎn)換。該研究不僅提供了同一種外界環(huán)境因子（CO2）如何調(diào)控兩個(gè)截然不同的生理過(guò)程（“酵母-菌絲形態(tài)”和“白菌-灰菌”轉(zhuǎn)換）的一個(gè)范例，也為病原真菌致病機(jī)理和高等生物CO2感應(yīng)研究提供了線(xiàn)索,。相關(guān)研究得到了英國(guó)肯特大學(xué)部分合作者的支持,。
該項(xiàng)研究成果已在線(xiàn)發(fā)表在Molecular Biology of the Cell上。（生物谷Bioon.com）
doi:10.1091/mbc.E12-02-0094
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The transcription factor Flo8 mediates CO2 sensing in the human fungal pathogen Candida albicans
Han Du1, Guobo Guan1, Jing Xie1,2, Fabien Cottier3, Yuan Sun1, Wei Jia1, Fritz A. Mühlschlegel3,4, and Guanghua Huang1,*
Physiological levels of CO2 have a profound impact on prominent biological attributes of the major fungal pathogen of humans, Candida albicans. Elevated CO2 induces filamentous growth and promotes white-to-opaque switching. However, the underlying molecular mechanisms of CO2 sensing in C. albicans are insufficiently understood. Here we have identified the transcription factor Flo8 as a key regulator of CO2 induced morphogenesis in C. albicans by screening a gene null mutant library. We show that Flo8 is required for CO2 induced white-to-opaque switching as well as filamentous growth. Ectopic expression of FLO8 hypersensitizes C. albicans cells to the elevated CO2 levels. Furthermore we demonstrate that CO2 signaling in C. albicans involves two pathways: the already reported cAMP/PKA and another major unidentified. The two pathways converge on the transcription factor Flo8, which is the master regulator of CO2 sensing in C. albicans and plays a critical role in regulation of white/opaque switching and filamentous growth. Our findings provide new insights into the understanding of CO2 sensing in pathogenic fungi which has important implications for higher organisms.
