Xu Xingye, Liu Tao, Yang Jian, Chen Lihong, Liu Bo, Wei Candong, Wang Lingling, Jin Qi
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 6, Rongjing East Street, BDA, Beijing, 100176, China.
BMC Genomics. 2017 Aug 4;18(1):577. doi: 10.1186/s12864-017-3977-y.
Dermatophytes, the most common cause of fungal infections, affect millions of individuals worldwide. They pose a major threat to public health because of the severity and longevity of infections caused by dermatophytes and their refractivity to therapy. Trichophyton rubrum (T. rubrum), the most common dermatophyte species, is a promising model organism for dermatophyte research. Post-translational modifications (PTMs) have been shown to be essential for many biological processes, particularly in the regulation of key cellular processes that contribute to pathogenicity. Although PTMs have important roles, little is known about their roles in T. rubrum and other dermatophytes. Succinylation is a new PTM that has recently been identified. In this study, we assessed the proteome-wide succinylation profile of T. rubrum. This study sought to systematically identify the succinylated sites and proteins in T. rubrum and to reveal the roles of succinylated proteins in various cellular processes as well as the differences in the succinylation profiles in different growth stages of the T. rubrum life cycle.
A total of 569 succinylated lysine sites were identified in 284 proteins. These succinylated proteins are involved in various cellular processes, such as metabolism, translation and epigenetic regulation. Additionally, 24 proteins related to pathogenicity were found to be succinylated. Comparison of the succinylome at the conidia and mycelia stages revealed that most of the succinylated proteins and sites were growth-stage specific. In addition, the succinylation modifications on histone and ribosomal proteins were significantly different between these two growth stages. Moreover, the sequence features surrounding the succinylated sites were different in the two stages, thus indicating the specific recognition of succinyltransferases in each growth phase.
In this study, we explored the first T. rubrum succinylome, which is also the first PTM analysis of dermatophytes reported to date. These results revealed the major roles of the succinylated proteins involved in T. rubrum and the differences in the succinylomes between the two major growth stages. These findings should improve understanding of the physiological and pathogenic properties of dermatophytes and facilitate future development of novel drugs and therapeutics for treating superficial fungal infections.
皮肤癣菌是真菌感染最常见的病因,影响着全球数百万人。由于皮肤癣菌引起的感染严重且持久,以及它们对治疗的耐药性,它们对公众健康构成了重大威胁。红色毛癣菌(T. rubrum)是最常见的皮肤癣菌物种,是皮肤癣菌研究中一种很有前景的模式生物。翻译后修饰(PTM)已被证明对许多生物学过程至关重要,特别是在调控有助于致病性的关键细胞过程中。尽管PTM具有重要作用,但关于它们在红色毛癣菌和其他皮肤癣菌中的作用却知之甚少。琥珀酰化是最近才被发现的一种新的PTM。在本研究中,我们评估了红色毛癣菌全蛋白质组的琥珀酰化谱。本研究旨在系统地鉴定红色毛癣菌中的琥珀酰化位点和蛋白质,揭示琥珀酰化蛋白质在各种细胞过程中的作用,以及红色毛癣菌生命周期不同生长阶段琥珀酰化谱的差异。
在284种蛋白质中总共鉴定出569个琥珀酰化赖氨酸位点。这些琥珀酰化蛋白质参与各种细胞过程,如代谢、翻译和表观遗传调控。此外,发现24种与致病性相关的蛋白质被琥珀酰化。分生孢子和菌丝体阶段琥珀酰化蛋白质组的比较表明,大多数琥珀酰化蛋白质和位点具有生长阶段特异性。此外,这两个生长阶段之间组蛋白和核糖体蛋白上的琥珀酰化修饰存在显著差异。而且,两个阶段中琥珀酰化位点周围的序列特征不同,从而表明每个生长阶段中琥珀酰转移酶的特异性识别。
在本研究中,我们探索了首个红色毛癣菌琥珀酰化蛋白质组,这也是迄今为止报道的首个皮肤癣菌的PTM分析。这些结果揭示了参与红色毛癣菌的琥珀酰化蛋白质的主要作用以及两个主要生长阶段之间琥珀酰化蛋白质组的差异。这些发现应有助于增进对皮肤癣菌生理和致病特性的理解,并促进未来治疗浅表真菌感染的新型药物和疗法的开发。