金黄色葡萄球菌壁磷壁酸致病与免疫的分子机制研究进展

Role of Staphylococcus aureus wall teichoic acids in pathogenicity and host immune response

摘要:

金黄色葡萄球菌(Staphylococcus aureus)壁磷壁酸(wall teichoic acids, WTAs)是多元醇经由磷酸二酯键共价连接组成的细胞壁表面阴离子糖类聚合物，参与调节细胞壁的稳态并介导细菌毒力。金黄色葡萄球菌WTAs与宿主细胞表面特定的受体结合，可诱导天然免疫和获得性免疫应答。此外，金黄色葡萄球菌WTAs还参与调控毒力基因的表达，有助于细菌的定殖感染，在基因工程靶标治疗和噬菌体药物治疗方面具有广泛的应用前景。本文对金黄色葡萄球菌WTAs的合成进行了概述，综述了WTAs对宿主免疫应答的调控作用，以及在细菌对宿主侵袭与定殖中的致病机制，并归纳WTAs的耐药分子机制和作为药物治疗靶标的研究现状。这些研究为揭示WTAs的致病与免疫分子机制提供研究思路，为预防和治疗金黄色葡萄球菌的感染提供新的策略。

关键词:壁磷壁酸;金黄色葡萄球菌;糖基化修饰;免疫细胞;免疫调节;药物靶标

Abstract:

Staphylococcus aureus wall teichoic acids (WTAs) are the anionic glycopolymers containing phosphodiester-linked polyol units and contribute to the cell wall homeostasis, virulence, and pathogenicity of S. aureus after glycosylation. As the key targets of receptor binding sites and crucial antigenic epitopes in the host, S. aureus WTAs induce not only the secretion of pro-inflammatory cytokines in the innate immune system but also specific antibody response in the adaptive immune system. Furthermore, the WTAs promote S. aureus colonization by regulating the expression of virulence genes, thus demonstrating a great prospect as the targets in genetic engineering and phage therapy. We overview the biosynthesis of S. aureus WTAs, elaborate on the WTA-induced immunomodulation of host, and introduce the roles of WTAs in the invasion and colonization of S. aureus. Further, we summarize the mechanisms of the drug resistance of S. aureus WTAs and the research progress in the application of S. aureus WTAs as the targets in the development of novel therapies. This review aims to provide reference for deciphering the molecular mechanism of the pathogenicity of S. aureus WTAs and the corresponding host responses, as well as the development of preventative and therapeutic approaches against S. aureus-mediated diseases.

Key words:wall teichoic acid;Staphylococcus aureus;glycosylation;immune cell;immunomodulation;drug target