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The stuA gene controls development, adaptation, stress tolerance, and virulence of the dermatophyte Trichophyton rubrum
Microbiological Research ( IF 6.1 ) Pub Date : 2020-09-18 , DOI: 10.1016/j.micres.2020.126592
Elza A.S. Lang , Tamires A. Bitencourt , Nalu T.A. Peres , Lucia Lopes , Larissa G. Silva , Rodrigo A. Cazzaniga , Antonio Rossi , Nilce M. Martinez-Rossi

The APSES family, comprising of the transcriptional regulators Asm1p, Phd1p, Sok2p, Efg1p, and StuA, is found exclusively in fungi and has been reported to control several cellular processes in these organisms. However, its function in dermatophytes has not yet been completely understood. Here, we generated two null mutant strains by deleting the stuA gene in the dermatophyte Trichophyton rubrum, the most common clinical isolate obtained from human skin and nail mycoses. The functional characterization of the knocked-out strains revealed the involvement of stuA in germination, morphogenesis of conidia and hyphae, pigmentation, stress responses, and virulence. Although the mutant strains could grow under several nutritional conditions, growth on the keratin medium, human nails, and skin was impaired. The co-culture of stuA mutants with human keratinocytes revealed enhanced development. Moreover, a stuA mutant grown on the keratin substrate showed a marked decrease in the transcript numbers of the hydrophobin encoding gene (hypA), suggesting the involvement of stuA in the molecular mechanisms underlying mechanosensing during the fungi-host interaction. In addition, bioinformatics analyses revealed the potential involvement of StuA in different biological processes such as oxidation-reduction, phosphorylation, proteolysis, transcription/translation regulation, and carbohydrate metabolism. Cumulatively, the present study suggested that StuA is a crosstalk mediator of many pathways and is an integral component of the infection process, implying that it could be a potential target for antifungal therapy.



中文翻译:

STUA基因控制发展,适应,抗逆性和毒力的皮肤癣菌红色毛癣菌

仅在真菌中发现了由转录调节因子A sm1p,P hd1p,S ok2p,E fg1p和S tuA组成的APSES家族,据报道可控制这些生物体中的几个细胞过程。然而,其在皮肤真菌中的功能尚未被完全理解。在这里,我们删除了皮肤癣菌毛癣菌中stuA基因,从而产生了两个无效的突变菌株,后者是从人类皮肤和指甲真菌病中获得的最常见的临床分离株。敲除菌株的功能表征揭示了stuA的参与萌发,分生孢子和菌丝的形态发生,色素沉着,应激反应和毒力。尽管突变菌株可以在几种营养条件下生长,但在角蛋白培养基,人指甲和皮肤上的生长受到损害。stuA突变体与人角质形成细胞的共培养揭示了增强的发育。此外,生长在角蛋白底物上的stuA突变体显示疏水蛋白编码基因(hypA)的转录本数量显着减少,表明stuA的参与真菌与宿主相互作用过程中机械传感的分子机制 此外,生物信息学分析显示StuA可能参与了不同的生物过程,例如氧化还原,磷酸化,蛋白水解,转录/翻译调节和碳水化合物代谢。累计地,本研究表明StuA是许多途径的串扰介体,并且是感染过程的组成部分,这暗示它可能是抗真菌治疗的潜在靶标。

更新日期:2020-09-20
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