Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
复制标题
DOI：
10.1038/s41598-020-66620-7
复制
发表时间：
2020-06-17
影响因子：
4.6
通讯作者：
Mukae，Hiroshi
中科院分区：
文献类型：
--
作者：
Ito，Yuya;Miyazaki，Taiga;Mukae，Hiroshi
Elm1 是一种丝氨酸/苏氨酸激酶，参与多种细胞功能，包括酿酒酵母的胞质分裂、形态发生和耐药性；然而，其在病原真菌中的作用尚未见报道。在这项研究中，我们在临床上重要的真菌病原体光滑念珠菌中创建了ELM1缺失、ELM1重建、ELM1过表达和ELM1激酶死亡菌株，并研究了Elm1在细胞形态、应激反应和毒力中的作用。 Theelm1Δ菌株表现出细长的形态和更厚的细胞壁，对细胞壁成分的分析表明，相对于野生型和ELM1过表达菌株，该菌株表现出显着增加的几丁质含量。尽管theelm1Δ菌株比其他两种菌株表现出更慢的生长，并且对高温和细胞壁损伤剂的敏感性增加，但它在大蜡螟感染模型中表现出更强的毒力。此外，Elm1 的缺失导致对琼脂板和上皮细胞的粘附增加，而这代表了艰难梭菌的重要毒力因子。光滑。此外，RNA测序显示，elm1Δ菌株中30个粘附样基因的表达水平升高。重要的是，所有这些功能都是由 Elm1 的激酶活性介导的。据我们所知，这是第一份描述 Elm1 在病原真菌中功能特征的报告。
Elm1 is a serine/threonine kinase involved in multiple cellular functions, including cytokinesis, morphogenesis, and drug resistance inSaccharomyces cerevisiae; however, its roles in pathogenic fungi have not been reported. In this study, we createdELM1-deletion,ELM1-reconstituted,ELM1-overexpression, andELM1-kinase-dead strains in the clinically important fungal pathogenCandida glabrataand investigated the roles of Elm1 in cell morphology, stress response, and virulence. Theelm1Δstrain showed elongated morphology and a thicker cell wall, with analyses of cell-wall components revealing that this strain exhibited significantly increased chitin content relative to that in the wild-type andELM1-overexpression strains. Although theelm1Δstrain exhibited slower growth than the other two strains, as well as increased sensitivity to high temperature and cell-wall-damaging agents, it showed increased virulence in aGalleria mellonella-infection model. Moreover, loss of Elm1 resulted in increased adhesion to agar plates and epithelial cells, which represent important virulence factors inC. glabrata. Furthermore, RNA sequencing revealed that expression levels of 30 adhesion-like genes were elevated in theelm1Δstrain. Importantly, all these functions were mediated by the kinase activity of Elm1. To our knowledge, this is the first report describing the functional characterization of Elm1 in pathogenic fungi.