cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans.
cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans.
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DOI：
10.1111/mmi.13588
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发表时间：
2017-03
影响因子：
3.6
通讯作者：
Konopka JB
中科院分区：
文献类型：
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作者：
Parrino SM;Si H;Naseem S;Groudan K;Gardin J;Konopka JB
真菌病原体白色念珠菌可以从出芽过渡到菌丝生长，从而促进生物膜的形成和侵入性生长到组织中。刺激腺苷酸环化酶形成cAMP可诱导菌丝形态发生。缺乏腺苷酸环化酶（cyr1Δ）的细胞不能形成菌丝，这表明cAMP信号传导对菌丝生长至关重要。然而，cyr1Δ突变体也生长缓慢且形态发生缺陷，这使得人们不清楚菌丝诱导剂是否必须刺激cAMP，或者是否需要正常基础水平的cAMP来维持菌丝生长所需的细胞健康。有趣的是，补充低水平cAMP的cyr1Δ细胞使它们能够响应诱导剂n -乙酰氨基葡萄糖（GlcNAc）形成菌丝，这表明基础水平的cAMP足以刺激。此外，我们分离出生长速度更快的cyr1Δ伪逆转菌株，即使缺乏cAMP也能诱导形成菌丝。假逆转菌株不是由CO2诱导的，这与CO2直接刺激腺苷酸环化酶的报道一致。突变分析表明，假逆转录菌株的菌丝诱导不依赖于RAS1，但依赖于蛋白激酶a下游的EFG1转录因子。因此，camp无关的信号有助于菌丝反应的诱导。cAMP信号通路诱导从出芽到菌丝形态发生的转换，促进人类真菌白色念珠菌生物膜的形成和侵袭性生长。在这项研究中，我们发现了在没有腺苷酸环化酶的情况下可以形成菌丝的假逆转菌株，这表明camp非依赖性途径也有助于这种形态转换。
The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase (cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth. Interestingly, supplementation of cyr1Δ cells with low levels of cAMP enabled them to form hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a basal level of cAMP is sufficient for stimulation. Furthermore, we isolated faster-growing cyr1Δ pseudorevertant strains that can be induced to form hyphae even though they lack cAMP. The pseudorevertant strains were not induced by CO2, consistent with reports that CO2 directly stimulates adenylyl cyclase. Mutational analysis showed that induction of hyphae in a pseudorevertant strain was independent of RAS1, but was dependent on the EFG1 transcription factor that acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to the induction of hyphal responses. The cAMP signaling pathway induces a switch from budding to hyphal morphogenesis that promotes biofilm formation and invasive growth by the human fungal pathogen Candida albicans. In this study we identified pseudorevertant strains that can form hyphae in the absence of adenylyl cyclase, which indicates that cAMP-independent pathways also contribute to this morphological switch.