Valsecchi Isabel, Sarikaya-Bayram Özlem, Wong Sak Hoi Joanne, Muszkieta Laetitia, Gibbons John, Prevost Marie-Christine, Mallet Adeline, Krijnse-Locker Jacomina, Ibrahim-Granet Oumaima, Mouyna Isabelle, Carr Paul, Bromley Michael, Aimanianda Vishukumar, Yu Jae-Hyuk, Rokas Antonis, Braus Gerhard H, Saveanu Cosmin, Bayram Özgür, Latgé Jean Paul
Unité des Aspergillus, Institut Pasteur, Paris 75015, France.
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
Mol Microbiol. 2017 Sep;105(6):880-900. doi: 10.1111/mmi.13744. Epub 2017 Jul 21.
Aspergillus fumigatus, a ubiquitous human fungal pathogen, produces asexual spores (conidia), which are the main mode of propagation, survival and infection of this human pathogen. In this study, we present the molecular characterization of a novel regulator of conidiogenesis and conidial survival called MybA because the predicted protein contains a Myb DNA binding motif. Cellular localization of the MybA::Gfp fusion and immunoprecipitation of the MybA::Gfp or MybA::3xHa protein showed that MybA is localized to the nucleus. RNA sequencing data and a uidA reporter assay indicated that the MybA protein functions upstream of wetA, vosA and velB, the key regulators involved in conidial maturation. The deletion of mybA resulted in a very significant reduction in the number and viability of conidia. As a consequence, the ΔmybA strain has a reduced virulence in an experimental murine model of aspergillosis. RNA-sequencing and biochemical studies of the ΔmybA strain suggested that MybA protein controls the expression of enzymes involved in trehalose biosynthesis as well as other cell wall and membrane-associated proteins and ROS scavenging enzymes. In summary, MybA protein is a new key regulator of conidiogenesis and conidial maturation and survival, and plays a crucial role in propagation and virulence of A. fumigatus.
烟曲霉是一种常见的人类真菌病原体，可产生无性孢子（分生孢子），这是该人类病原体的主要传播、存活和感染方式。在本研究中，我们展示了一种名为MybA的新型分生孢子形成和分生孢子存活调节因子的分子特征，因为预测的蛋白质含有一个Myb DNA结合基序。MybA::Gfp融合蛋白的细胞定位以及MybA::Gfp或MybA::3xHa蛋白的免疫沉淀表明MybA定位于细胞核。RNA测序数据和uidA报告基因检测表明，MybA蛋白在wetA、vosA和velB（参与分生孢子成熟的关键调节因子）的上游发挥作用。mybA的缺失导致分生孢子的数量和活力显著减少。因此，ΔmybA菌株在实验性小鼠曲霉病模型中的毒力降低。对ΔmybA菌株的RNA测序和生化研究表明，MybA蛋白控制参与海藻糖生物合成的酶以及其他细胞壁和膜相关蛋白和ROS清除酶的表达。总之，MybA蛋白是分生孢子形成、分生孢子成熟和存活的新关键调节因子，在烟曲霉的传播和毒力中起关键作用。
