Long-distance early endosome motility in Aspergillus fumigatus promotes normal hyphal growth behaviors in controlled microenvironments but is dispensable for virulence
Long-distance early endosome motility in Aspergillus fumigatus promotes normal hyphal growth behaviors in controlled microenvironments but is dispensable for virulence
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DOI：
10.1111/tra.12735
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发表时间：
2020-05-25
期刊：
影响因子：
4.5
通讯作者：
Egan, Martin John
中科院分区：
文献类型：
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作者：
Bieger, Baronger Dowell;Rogers, Audra Mae;Egan, Martin John
在丝状真菌中，早期内体通过基于微管的马达蛋白不断地运输到生长的菌丝尖端，并从生长的菌丝尖端运输，作为各种货物的长距离运输平台，包括mRNA，信号分子和其他搭便车的细胞器。虽然丝状真菌中早期内体运动的细胞机制相当好地表征，但该过程的更广泛的生理意义仍然不太清楚。我们着手确定烟曲霉（Aspergillus fumigatus）中长距离早期内体运输的重要性，烟曲霉是一种机会性人类致病真菌，可在免疫功能低下的个体中引起毁灭性的肺部感染。我们首先在A. fumigatus，然后产生了一种突变体，其中早期内体运动性通过靶向缺失编码FtsA的基因而受到严重干扰，FtsA是将早期内体与其马达蛋白连接的蛋白质复合物之一。使用基于微流体的方法，我们表明，接触诱导的菌丝分支行为受损的三角洲ftsA突变体，但FtsA介导的早期内体运动是无脊椎动物感染模型中的毒力。总的来说，我们的研究提供了一个重要的人类病原真菌早期内体运动的新见解。
In filamentous fungi, early endosomes are continuously trafficked to, and from, the growing hyphal tip by microtubule-based motor proteins, serving as platforms for the long-distance transport of diverse cargos including mRNA, signaling molecules, and other organelles which hitchhike on them. While the cellular machinery for early endosome motility in filamentous fungi is fairly well characterized, the broader physiological significance of this process remains less well understood. We set out to determine the importance of long-distance early endosome trafficking in Aspergillus fumigatus, an opportunistic human pathogenic fungus that can cause devastating pulmonary infections in immunocompromised individuals. We first characterized normal early endosome motile behavior in A. fumigatus, then generated a mutant in which early endosome motility is severely perturbed through targeted deletion of the gene encoding for FtsA, one of a complex of proteins that links early endosomes to their motor proteins. Using a microfluidics-based approach we show that contact-induced hyphal branching behaviors are impaired in Delta ftsA mutants, but that FtsA-mediated early endosome motility is dispensable for virulence in an invertebrate infection model. Overall, our study provides new insight into early endosome motility in an important human pathogenic fungus.