浙江大学医学院王本课题组取得一项新突破。他们的最新研究揭示了诱导细菌钙化对耐甲氧西林金黄色葡萄球菌的系统治疗和免疫调节。该研究于2025年7月15日发表于国际一流学术期刊《自然—生物技术》杂志上。

在本研究中，该课题组将金黄色葡萄球菌壁磷壁酸单克隆抗体的抗原结合片段与聚唾液酸交联，形成抗体PSA偶联物，能有效靶向并诱导MRSA表面钙化。这个过程通过阻碍MRSA的能量代谢和多种必要的代谢途径来消除细菌。课题组研究人员发现细菌钙化导致体内巨噬细胞和单核细胞中钙保护蛋白S100A8/S100A9的表达增加，并能刺激巨噬细胞激活至炎症状态，从而促进细菌根除，作为免疫调节剂。全身性给药PSA偶联物对MRSA诱导的小鼠慢性肺部感染和慢性骨髓炎具有较高的疗效和安全性。本研究为耐药菌及相关难治性致病性感染的治疗提供了一种有前景的治疗方法。

据了解，耐甲氧西林金黄色葡萄球菌（MRSA）由于抗生素耐药性已成为全球最致命的细菌之一。

附：英文原文

Title: Inducing bacterial calcification for systematic treatment and immunomodulation against methicillin-resistant Staphylococcus aureus

Author: Zhang, Wanying, Liu, Liang, Zhang, Qingyan, Lu, Huidan, Li, Anyao, Huang, Yuqiao, Zhang, Wenting, Li, Hanhui, Lu, Xiaoyan, Ming, Xinliang, Yang, Ze, Shou, Hao, Wang, Yilin, Xia, Jingyan, Xu, Feng, Wang, Ben

Issue&Volume: 2025-07-15

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the deadliest bacteria globally due to antibiotic resistance. In this study, we crosslinked antigen-binding fragments of monoclonal antibodies against the wall-teichoic acid of S. aureus with polysialic acid to form an antibodyPSA conjugate, which can effectively target and induce calcification on the surface of MRSA. This process eliminates bacteria by hindering the energy metabolism and multiple essential metabolic pathways of MRSA. We found that bacterial calcification leads to increased expression of calprotectin, S100A8/S100A9, in macrophages and monocytes in vivo and can stimulate the activation of macrophages to an inflammatory state, thereby promoting bacterial eradication as an immunomodulator. Systemic administration of the antibodyPSA conjugate demonstrates high efficacy and safety for treating chronic lung infections and chronic osteomyelitis caused by MRSA in mice. This study offers a promising therapy for treating drug-resistant bacteria and related refractory pathogenic infections.

DOI: 10.1038/s41587-025-02736-3

Source: https://www.nature.com/articles/s41587-025-02736-3