Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2023-12-19 DOI:10.1007/s12275-023-00096-8

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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.

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转录因子 Tec1 和 Tec2 通过线粒体氧化代谢的增加在卢氏粘菌的茎髓生长和病毒性中发挥关键作用

摘要粘孢子菌病是由粘孢子菌目真菌引起的一种致命且难以治疗的真菌感染。黏菌目成员之一的卢氏黏菌通常被用作了解疾病发病机制的模型。然而，人们对粘菌目真菌的头状花序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. lusitanicus 的头状茎发育和毒力中的作用。与子囊菌属和担子菌属基因组中只有一个Tec同源物不同，在粘菌属基因组中发现了两个Tec同源物，即Tec1和Tec2，只有Phycomyces blakesleeanus基因组中只有一个Tec同源物。lusitanicus 的菌丝生长、线粒体含量和活性、根瘤铁蛋白合成酶编码基因 rfs 的表达以及对线虫和蜡蛾幼虫的毒力均有所增加，但 cAMP 水平和蛋白激酶 A（PKA）活性却有所下降。此外，tec1 和 tec2 基因表达株需要足够的线粒体代谢来促进毒力表型。异三聚体 G beta 亚基 1 编码基因缺失株（Δgpb1）增加了 cAMP-PKA 活性，下调了两个 tec 基因，降低了毒力和芽孢发育，但 tec1 和 tec2 的过表达恢复了这些缺陷。在 PKA 的推定磷酸化位点上过量表达 Tec1（S332A）和 Tec2（S168A）的等位基因突变变体可提高 Δgpb1 的毒力和菌丝生长。这些发现表明，Tec 同源物通过增强线粒体代谢和根瘤铁蛋白积累来促进菌丝发育和毒力，为合理控制 M. lusitanicus 的毒力表型提供了新的信息。

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