Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G‐protein beta subunits (Gpb1, Gpb2 and Gpb3). The Gpb1‐encoding gene is up‐regulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations. Infection assays in mice indicated a phenotype with considerably reduced virulence and tissue invasiveness in the deletion mutants (Δgpb1) and decreased host inflammatory response. This finding could be attributed to the reduced filamentous growth in animal tissues compared with that of the wild‐type strain. Mutation in a regulatory subunit of cAMP‐dependent protein kinase A (PKA) subunit (PkaR1) resulted in similar phenotypes to Δgpb1. The defects exhibited by the Δgpb1 strain were genetically suppressed by pkaR1 overexpression, indicating that the PKA pathway is controlled by Gpb1 in M. circinelloides. Moreover, during growth under low oxygen levels, cAMP levels were much higher in the Δgpb1 than in the wild‐type strain, but similar to those in the ΔpkaR1 strain. These findings reveal that M. circinelloides possesses a signal transduction pathway through which the Gpb1 heterotrimeric G subunit and PkaR1 control mycelial growth in response to low oxygen levels.

中文翻译：

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异源三聚体 G 蛋白 β 亚基 Gpb1 通过蛋白激酶 A 途径控制低氧条件下的菌丝生长，并且对真菌毛霉菌 circinelloides 的毒力至关重要。

Mucor circinelloides是一种二态性机会致病菌，表达三个异源三聚体 G 蛋白 β 亚基（Gpb1、Gpb2 和 Gpb3）。与孢子或酵母阶段相比，Gpb1 编码基因在菌丝体生长过程中上调。gpb1缺失突变分析揭示了它与二态转变期间的充分发育和低氧浓度下菌丝生长的相关性。小鼠感染试验表明，缺失突变体（Δ gpb1) 和减少宿主炎症反应。这一发现可能归因于与野生型菌株相比，动物组织中的丝状生长减少。cAMP 依赖性蛋白激酶 A (PKA) 亚基 (PkaR1) 调节亚基的突变导致与 Δ gpb1相似的表型。Δ gpb1菌株表现出的缺陷被pkaR1过表达基因抑制，表明 PKA 途径受M. circinelloides 中的 Gpb1 控制。此外，在低氧水平下的生长过程中，Δ gpb1中的cAMP 水平远高于野生型菌株，但与 Δ pkaR1菌株中的相似。这些发现表明M. circinelloides具有信号转导通路，Gpb1 异源三聚体 G 亚基和 PkaR1 通过该通路控制菌丝体生长以响应低氧水平。