金黄色葡萄球菌毒素-抗毒素系统的生存适应与致病机制研究进展

doi:10.3969/j.issn.1674-8115.2026.07.002

摘要/Abstract

摘要：

毒素-抗毒素系统（toxin-antitoxin systems，TAS）广泛存在于细菌与古菌中，通常由抑制细菌生长的毒素及中和毒素毒性的抗毒素组成，是调控细菌生长代谢及致病过程的关键分子枢纽。金黄色葡萄球菌（Staphylococcus aureus，简称金葡菌）是临床重要病原菌，可引起从皮肤软组织感染至脓毒症、心内膜炎等多种疾病。研究显示，TAS在金葡菌抵抗外界压力、产生抗生素耐受、形成持留菌以及生物被膜发育等进程中发挥着重要作用，但相关分子机制尚未完全明确。深入阐明相关分子机制，是理解金葡菌致病特性以及开发新型抗菌策略的关键所在。该文综述了TAS的分型特征及其在金葡菌适应性生存与毒力调控方面的功能，重点探讨了TAS介导的持留菌形成、抗生素耐受及生物被膜发育机制。在营养缺乏或面临抗生素压力时，TAS通过干扰DNA复制、抑制蛋白质合成等核心代谢通路，诱导细菌进入代谢休眠状态，进而导致表型耐受以及持留菌的形成，帮助金葡菌实现适应性生存。该系统还能够通过全局调控网络影响毒力因子的表达，部分TAS编码的毒素具备直接破坏真核细胞膜的能力，可导致宿主细胞裂解，促进细菌的侵袭和扩散。此外，由Ⅶ型分泌系统介导的毒素分泌，还能为金葡菌在微生物群落中赋予竞争优势。该文系统梳理了金葡菌中不同类型TAS的结构特征与作用模式，旨在深化对金葡菌致病机制的认识，同时为开发以TAS为靶点的新型抗菌策略提供理论参考与研究方向。

关键词: 金黄色葡萄球菌, 毒素-抗毒素系统, 持留菌, 生物被膜, 细菌致病

Abstract:

Toxin-antitoxin systems (TAS) are widely distributed in bacteria and archaea, typically consisting of a toxin that inhibits bacterial growth and a cognate antitoxin that neutralizes its toxicity. These systems have been recognized as key regulators of bacterial growth, metabolism, and pathogenesis. Staphylococcus aureus (S. aureus) is an important clinical pathogen that can cause a wide range of diseases, ranging from skin and soft tissue infections to sepsis and endocarditis. Studies have shown that TAS play important roles in stress resistance, persister cell formation, and biofilm development in S. aureus. Elucidating the underlying molecular mechanisms is essential for understanding the pathogenic characteristics of S. aureus and for developing novel antibacterial strategies. Here, This review summarizes the classification and structural features of TAS in S. aureus and discuss their functions in adaptive survival and virulence regulation. It focuses on how, under nutrient limitation or antibiotic pressure, TAS interfere with DNA replication and protein synthesis to induce a metabolically dormant state, thereby contributing to phenotypic tolerance and persister cell formation. This review further describes how TAS modulate virulence factor expression through global regulatory networks and how certain TAS-encoded toxins directly damage eukaryotic membranes to promote bacterial invasion and dissemination. Additionally, it highlights the contribution of the type Ⅶ secretion system to toxin export, which provides a competitive advantage to S. aureus within polymicrobial communities. This review systematically summarizes the structural characteristics and functional modes of different types of TAS in S. aureus, aiming to deepen the understanding of its pathogenic mechanisms and to provide theoretical references and research directions for the development of novel TAS-targeted antibacterial strategies.

Key words: Staphylococcus aureus, toxin-antitoxin system, persister cell, biofilm, pathogenicity

中图分类号:

R378.11

谢忻妮, 吕言, 李敏, 王亚楠. 金黄色葡萄球菌毒素-抗毒素系统的生存适应与致病机制研究进展[J]. 上海交通大学学报（医学版）, 2026, 46(7): 839-846.

Xie Xinni, Lü Yan, Li Min, Wang Yanan. Research progress in adaptive survival and pathogenic mechanisms of toxin-antitoxin systems in Staphylococcus aureus[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(7): 839-846.

图/表 3

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Type	Toxin	Antitoxin	Characteristic	Representative TAS in S. aureus
Ⅰ	mRNA	Antisense RNA	The toxin is a small peptide encoded by an mRNA. A complementary antisense RNA antitoxin inhibits toxin translation through base pairing	sprG1/sprF1^[18], sprA1/sprA2^[19]
Ⅱ	Protein	Protein	Both toxin and antitoxin are proteins. The antitoxin neutralizes the toxin through direct protein-protein interaction	MazEF^[20], YefM-YoeB^[21], HigBA^[22]
Ⅲ	Protein	RNA	A protein toxin is inactivated by an RNA antitoxin that binds to it, inducing conformational inactivation ^[23]	TenpIN^[24]
Ⅳ	Protein	Protein	The protein antitoxin inhibits the toxin indirectly by blocking its interaction with the cellular target rather than by direct binding	Not reported
Ⅴ	Protein	Protein	The antitoxin acts as an RNase that specifically cleaves the toxin mRNA, thereby preventing toxin synthesis	Not reported
Ⅵ	Protein	Protein	The antitoxin promotes protease-mediated degradation of the toxin protein through direct interaction	Not reported
Ⅶ	Protein	Protein	The antitoxin inactivates the toxin by facilitating its post-translational modification	Not reported
Ⅷ	RNA	RNA	An RNA antitoxin inhibits either transcription of the toxin gene or neutralizes the toxin RNA through direct binding	Not reported

Type	Toxin	Antitoxin	Characteristic	Representative TAS in S. aureus
Ⅰ	mRNA	Antisense RNA	The toxin is a small peptide encoded by an mRNA. A complementary antisense RNA antitoxin inhibits toxin translation through base pairing	sprG1/sprF1^[18], sprA1/sprA2^[19]
Ⅱ	Protein	Protein	Both toxin and antitoxin are proteins. The antitoxin neutralizes the toxin through direct protein-protein interaction	MazEF^[20], YefM-YoeB^[21], HigBA^[22]
Ⅲ	Protein	RNA	A protein toxin is inactivated by an RNA antitoxin that binds to it, inducing conformational inactivation ^[23]	TenpIN^[24]
Ⅳ	Protein	Protein	The protein antitoxin inhibits the toxin indirectly by blocking its interaction with the cellular target rather than by direct binding	Not reported
Ⅴ	Protein	Protein	The antitoxin acts as an RNase that specifically cleaves the toxin mRNA, thereby preventing toxin synthesis	Not reported
Ⅵ	Protein	Protein	The antitoxin promotes protease-mediated degradation of the toxin protein through direct interaction	Not reported
Ⅶ	Protein	Protein	The antitoxin inactivates the toxin by facilitating its post-translational modification	Not reported
Ⅷ	RNA	RNA	An RNA antitoxin inhibits either transcription of the toxin gene or neutralizes the toxin RNA through direct binding	Not reported