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

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2025-07-15 DOI:10.1038/s41587-025-02736-3

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

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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 antibody‒PSA 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 antibody‒PSA 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.

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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

耐甲氧西林金黄色葡萄球菌（MRSA）已成为全球最致命的细菌之一，由于抗生素耐药性。本研究将金黄色葡萄球菌壁磷壁酸单克隆抗体抗原结合片段与聚唾液酸交联，形成抗体- psa偶联物，可有效靶向并诱导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。我们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。在治疗MRSA引起的小鼠慢性肺部感染和慢性骨髓炎方面，系统给药抗体- psa偶联物显示出高效率和安全性。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。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

期刊介绍： Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.