蛋白质翻译后修饰在水产病原菌致病机制中的研究进展

    The role of post-translational modifications in aquatic bacterial pathogens

    • 摘要:
      意义 细菌感染不仅严重威胁人类健康,也对水产养殖业造成重大损失。解析水产病原菌的分子致病机制是制定精准防控策略的核心环节。随着蛋白质组学和质谱技术的发展,蛋白质翻译后修饰(PTMs)逐渐被发现是调控病原菌致病过程的重要分子机制。因此,系统总结PTMs在水产病原菌致病机制中的研究进展,有助于深化对细菌感染机制的理解并为防治提供新思路。
      进展 研究表明,磷酸化、乙酰化、琥珀酰化及糖基化等PTMs广泛存在于水产病原菌中,通过调控蛋白质构象、活性及相互作用,影响其致病过程。在毒力调控方面,类核相关蛋白的乙酰化、琥珀酰化修饰可改变其DNA结合能力,进而调控毒力基因的沉默或激活;双组分系统(TCS)和群体感应(QS)信号通路的关键组分则通过磷酸化、乙酰化等修饰介导信号转导;转录因子的PTMs影响其稳定性及与DNA的结合能力以调控毒力因子的转录;而毒力因子本身的PTMs则直接调控其活性和感染能力。在病原宿主互作层面,PTMs不仅参与病原菌的代谢重编程与环境适应性调节,其表面结构蛋白及鞭毛的糖基化修饰会影响宿主免疫识别与细菌免疫逃逸;此外,宿主细胞能主动介导病原菌效应蛋白的PTMs,改变其亚细胞定位和功能,从而促进感染进程。不同类型PTMs之间常存在复杂的串扰关系,它们可在同一蛋白或同一位点上协同或拮抗作用,形成动态的修饰调控网络,这为病原菌适应宿主微环境并增强其感染力提供了重要的分子基础。
      展望 PTMs在水产病原菌致病机制中发挥关键作用,但当前研究仍局限于少数修饰类型和少数菌种。未来应拓展研究范围,结合多组学和感染模型揭示动态调控网络,并深入探索修饰间串扰机制。系统研究PTMs不仅有助于阐明病原菌致病机制,也可为水产病害防控提供特异性新靶点与理论依据。

       

      Abstract:
      Significance Bacterial infections pose a severe threat to human health and cause significant economic losses in aquaculture. Deciphering the molecular pathogenic mechanisms of aquatic bacterial pathogens is crucial for developing precise prevention and control strategies. With advancements in proteomics and mass spectrometry, post-translational modifications (PTMs) have emerged as pivotal molecular mechanisms regulating the pathogenic processes of these bacteria. Therefore, systematically summarizing research progress on PTMs in aquatic bacterial pathogenesis will deepen our understanding of infection mechanisms and provide novel insights for developing control measures.
      Progress Studies demonstrate that PTMs such as phosphorylation, acetylation, succinylation, and glycosylation are widespread in aquatic bacterial pathogens. These modifications influence pathogenesis by modulating protein conformation, activity, and interactions. In virulence regulation: Acetylation and succinylation of nucleoid-associated proteins (NAPs) alter their DNA-binding capacity, thereby regulating the silencing or activation of virulence genes. Key components of Two-Component Systems (TCS) and Quorum Sensing (QS) pathways undergo PTMs to mediate signal transduction. PTMs on transcription factors affect their stability and DNA-binding ability, modulating the transcription of virulence factors. Modifications on virulence factors themselves directly regulate their activity and infectivity. In pathogen-host interaction: PTMs participate in metabolic reprogramming and environmental adaptation of the pathogen. Glycosylation modifications of surface structural proteins and flagella impact host immune recognition and bacterial immune evasion. Notably, host cells can actively mediate PTMs on bacterial effector proteins, altering their subcellular localization and function to promote infection. Furthermore, complex crosstalk exists between different PTM types. They can act synergistically or antagonistically on the same protein or residue, forming dynamic regulatory networks that provide a molecular basis for pathogen adaptation to the host microenvironment and enhanced infectivity.
      Perspect While PTMs play critical roles in the pathogenesis of aquatic bacterial pathogens, current research remains largely confined to a limited number of modification types and bacterial species. Future studies should broaden the scope to include diverse PTMs and pathogens, integrate multi-omics approaches with relevant infection models to reveal dynamic regulatory networks, and deeply explore the mechanisms of PTM crosstalk. Systematic investigation of PTMs will not only elucidate bacterial pathogenic mechanisms but also offer novel targets and a theoretical foundation for controlling aquatic bacterial diseases.

       

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