Divergent Protein Kinase A isoforms co-ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus.
Divergent Protein Kinase A isoforms co-ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus.
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DOI：
10.1111/j.1365-2958.2010.07509.x
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发表时间：
2011-02
影响因子：
3.6
通讯作者：
Rhodes JC
中科院分区：
文献类型：
--
作者：
Fuller KK;Richie DL;Feng X;Krishnan K;Stephens TJ;Wikenheiser-Brokamp KA;Askew DS;Rhodes JC
烟曲霉的基因组编码cAMP依赖性蛋白激酶（PKA）的催化亚基的两种同种型。尽管I类亚型PkaC1的缺失导致毒力减弱，但II类亚基PkaC2的功能以前未被研究。在这份报告中，我们证明了这两种亚型的行动一致，以支持各种生理过程，促进这种病原体的毒力。而pkaC1和pkaC2单缺失突变体显示野生型分生孢子萌发，双缺失突变体在响应于环境营养的萌发延迟。此外，PkaC1和PkaC2相互作用，通过碳水化合物分解代谢途径正向调节通量，因此ΔpkaC1ΔpkaC2突变体无法在低葡萄糖浓度下生长。重要的是，在ΔpkaC1ΔpkaC2菌株中观察到的发芽能力降低和无法利用葡萄糖与突变体无法在小鼠模型中建立感染相关。相反，pkaC2的过表达既促进葡萄糖上的体外生长，又将与ΔpkaC1相关的真菌负荷和死亡率恢复到野生型生物体的水平。总而言之，这些数据证明了pkaC 2的功能能力，并强调了PKA介导的代谢控制在A的致病潜力中的重要性。烟熏。
The genome of Aspergillus fumigatus encodes two isoforms of the catalytic subunit of the cAMP-dependent Protein Kinase (PKA). Although deletion of the class I isoform, pkaC1, leads to an attenuation of virulence, the function of the class II subunit, PkaC2, was previously uninvestigated. In this report, we demonstrate that both isoforms act in concert to support various physiologic processes that promote the virulence of this pathogen. Whereas pkaC1 and pkaC2 single-deletion mutants display wild-type conidial germination, a double-deletion mutant is delayed in germination in response to environmental nutrients. Furthermore, PkaC1 and PkaC2 interact to positively regulate flux through the carbohydrate catabolic pathway and, consequently, the ΔpkaC1ΔpkaC2 mutant is unable to grow on low glucose concentrations. Importantly, the reduced germinative capacity and inability to utilize glucose observed for the ΔpkaC1ΔpkaC2 strain correlated with an inability of the mutant to establish infection in a murine model. Conversely, overexpression of pkaC2 both promotes the in vitro growth on glucose, and restores the fungal burden and mortality associated with the ΔpkaC1 to that of the wild-type organism. Taken together, these data demonstrate the functional capacity of pkaC2 and emphasize the importance of PKA-mediated metabolic control in the pathogenic potential of A. fumigatus.
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影响因子：
3.6
作者：
Chen, Daliang;Janganan, Thamarai K;Chen, Gongyou;Marques, Everaldo R;Kress, Marcia R;Goldman, Gustavo H;Walmsley, Adrian R;Borges-Walmsley, M Ines
通讯作者：
Borges-Walmsley, M Ines
影响因子：
3.6
作者：
d'Enfert, C;Bonini, BM;Terenzi, HF
通讯作者：
Terenzi, HF
影响因子：
--
作者：
Hicks, JK;D'Souza, CA;Heitman, J
通讯作者：
Heitman, J
影响因子：
11.6
作者：
Adachi, K;Hamer, JE
通讯作者：
Hamer, JE
影响因子：
10.5
作者：
GOLD, S;DUNCAN, G;KRONSTAD, J
通讯作者：
KRONSTAD, J