Abstract

Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.

中文翻译：

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转录因子 Tec1 和 Tec2 通过增加线粒体氧化代谢在 Lusitanicus 菌丝生长和毒力中发挥关键作用

摘要

毛霉菌病是一种致命且难以治疗的真菌感染，由毛霉目真菌引起。 毛霉毛霉目成员，通常用作了解疾病发病机制的模型。然而，人们对毛霉目菌丝生长和毒力的转录控制知之甚少。本研究旨在探讨属于TEA/ATTS转录因子家族的Tec蛋白在M的菌丝发育和毒力中的作用。卢西塔尼库斯。与子囊菌和担子菌的基因组中只有一个 Tec 同源物不同，在毛霉目基因组中，除了Phycomyces blakesleeanusPhycomyces blakesleeanus的基因组中发现了两个 Tec 同源物 Tec1 和 Tec2。 a>。M的毒力表型提供新信息。卢西塔尼库斯 的毒力和菌丝生长。这些研究结果表明，Tec同源物通过增强线粒体代谢和根铁蛋白积累来促进菌丝体发育和毒力，为合理控制gpb1 过度表达修复了这些缺陷。在假定的 PKA 磷酸化位点中过度表达 Tec1(S332A) 和 Tec2(S168A) 等位基因突变体可增加 Δ tec2 和 tec1 基因，降低毒力和菌丝发育，但 tec) 增加了 cAMP-PKA 活性，下调了两者gpb1- 过表达菌株需要足够的线粒体代谢才能促进毒力表型。异源三聚体 G beta 亚基 1 编码基因删除菌株 (Δtec2- 和 tec1的表达以及毒力线虫和蜡蛾幼虫，但降低了 cAMP 水平和蛋白激酶 A (PKA) 活性。此外，rfs 增加菌丝生长、线粒体含量和活性、根铁蛋白合成酶编码基因 中过度表达M。 lusitanicus 在 tec2 和 tec1，只有一个 Tec 同系物。