Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases
Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases
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DOI：
10.1111/j.1365-2958.2011.07946.x
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发表时间：
2012-02-01
影响因子：
3.6
通讯作者：
Wagener, Johannes
中科院分区：
文献类型：
--
作者：
Dichtl, Karl;Helmschrott, Christoph;Wagener, Johannes
真菌细胞壁是一种保守的、高度动态的结构，对真菌病原菌的毒力和生存力至关重要，是抗真菌药物的重要靶点。细胞壁完整性（CWI）信号通路调节细胞壁的形状和生物合成。在这项工作中，我们确定，本地化和功能特点的四个假定的CWI应力传感器的烟曲霉，空气中的机会人类病原体和侵袭性曲霉病的原因。我们表明，Wsc1是专门需要的棘白菌素抗真菌药的耐药性。MidA对于高温耐受性和对细胞壁干扰剂刚果红和荧光钙白色的抗性是特别需要的。Wsc 1、Wsc 3和MidA另外具有重叠的功能，并且是径向生长和分生孢子所必需的。我们还分析了三个Rho GTPases的作用，这些酶在其他真菌中与CWI信号传导有关。我们发现，Rho1是必不可少的，条件性下调rho1或删除rho2或rho4的结果在严重受损的CWI。我们的数据表明酵母和霉菌的CWI应力传感器之间的显着功能差异。
The fungal cell wall, a conserved and highly dynamic structure, is essential for virulence and viability of fungal pathogens and is an important antifungal drug target. The cell wall integrity (CWI) signalling pathway regulates shape and biosynthesis of the cell wall. In this work we identified, localized and functionally characterized four putative CWI stress sensors of Aspergillus fumigatus, an airborne opportunistic human pathogen and the cause of invasive aspergillosis. We show that Wsc1 is specifically required for resistance to echinocandin antifungals. MidA is specifically required for elevated temperature tolerance and resistance to the cell wall perturbing agents congo red and calcofluor white. Wsc1, Wsc3 and MidA additionally have overlapping functions and are redundantly required for radial growth and conidiation. We have also analysed the roles of three Rho GTPases that have been implicated in CWI signalling in other fungi. We show that Rho1 is essential and that conditional downregulation of rho1 or deletion of rho2 or rho4 results in severely impaired CWI. Our data indicate significant functional differences between the CWI stress sensors of yeasts and moulds.