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首页> 外文期刊>Infection and immunity >The Cyclic AMP-Dependent Protein Kinase A Network Regulates Development and Virulence in Aspergillus fumigatus
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The Cyclic AMP-Dependent Protein Kinase A Network Regulates Development and Virulence in Aspergillus fumigatus

机译：环AMP依赖蛋白激酶A网络调节烟曲霉的发展和毒力。

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Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. To determine the importance of the cyclic AMP (cAMP) signaling pathway for virulence, the pkaC1 gene encoding a protein kinase A (PKA) catalytic subunit was cloned and characterized. Deletion of pkaC1 led to reduced conidiation and growth. PKA activity was not detectable in ΔpkaC1, ΔgpaB, and ΔacyA mutant strains. gpaB and acyA encode a G protein α subunit involved in cAMP signal transduction and adenylate cyclase, respectively. Addition of cAMP led to PKA activity in crude extracts of both the ΔgpaB and ΔacyA strains but not in crude extracts of the ΔpkaC1 strain. These findings provide evidence that PKAC1 represents the predominant form of PKA under the conditions tested, and GPAB and ACYA are members of the cAMP signaling cascade. Analysis of a pksPp-lacZ gene fusion indicated that the expression of the pathogenicity determinant-encoding pksP gene was reduced in ΔpkaC1 mutant strains compared with the expression of the gene fusion in the parental strain. In a low-dose murine inhalation model, conidia of both the ΔpkaC1 and ΔgpaB mutant strains were almost avirulent. Taken together, these findings indicate that the cAMP-PKA signal transduction pathway is required for A. fumigatus pathogenicity.
机译：烟曲霉是免疫力低下宿主的重要病原体，可引起肺炎和侵入性传播疾病，死亡率很高。为了确定循环AMP（cAMP）信号通路对毒力的重要性，克隆并鉴定了编码蛋白激酶A（PKA）催化亚基的 pkaC1 基因。 pkaC1 的删除导致分生孢子的减少和生长。在Δ pkaC1 ，Δ gpaB 和Δ acyA 突变株中均未检测到PKA活性。 gpaB 和 acyA 分别编码参与cAMP信号转导和腺苷酸环化酶的G蛋白α亚基。 cAMP的添加导致Δ gpaB 和Δ acyA 菌株的粗提物中的PKA活性，而不是Δ pkaC1 菌株的粗提物中的PKA活性。 。这些发现提供了证据，即在所测试的条件下，PKAC1代表PKA的主要形式，而GPAB和ACYA是cAMP信号级联的成员。对 pksP p- lacZ 基因融合的分析表明，致病性决定子编码 pksP 基因的表达在Δ pkaC1中降低了突变菌株与亲本菌株中基因融合表达的比较。在小剂量小鼠吸入模型中，Δ pkaC1 和Δ gpaB 突变株的分生孢子几乎无毒。综上所述，这些发现表明 A需要cAMP-PKA信号转导途径。烟的致病性。

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