Cao Mingya, Wang Siyu, Zhou Shengke, Yan Min, Zou Yu, Cui Yuan, Lou Xinyu, Gao Yichang, Chen Ying, Han Zijing, Qian Yi, Chen Jingying, Li Xia
Joint National Laboratory for Antibody Drug Engineering, School of Medicine, Henan University, Kaifeng, China.
The First Affiliated Hospital of Henan University, Henan University, Kaifeng, China.
mSphere. 2025 Jan 28;10(1):e0072124. doi: 10.1128/msphere.00721-24. Epub 2024 Dec 19.
(), a gram-negative, black-pigmented anaerobe, is a major etiological agent and a leading cause of periodontitis. Fimbriae protein Mfa1 is a key virulence factor of and plays a crucial role in bacterial adhesion, colonization, biofilm formation, and persistent inflammation, making it a promising therapeutic target. However, the role of anti-Mfa1 antibodies and the underlying protective mechanisms remain largely unexplored. Here, we developed and characterized the monoclonal antibodies (mAbs) targeting the Mfa1 protein of . Function analysis showed that anti-Mfa1 mAbs mediated bacterial agglutination and inhibited adhesion to saliva-coated hydroxyapatite and host cells. Notably, anti-Mfa1 mAbs significantly reduced bacterial burden and alveolar bone loss in a -induced experimental periodontitis model. These results show that anti-Mfa1 mAbs can be beneficial in alleviating infections, and provide important insights for the development of adequate adjuvant treatment regimens for Mfa1-targeted therapeutics.
Fimbriae (pili) play an important role in bacterial adhesion, invasion of host cells and tissues, and formation of biofilms. Studies have shown that two types of fimbriae of , FimA and Mfa1, are important for colonization and infection through their binding to host tissues and other bacteria. While anti-FimA antibodies have been shown to improve periodontitis, the effect of anti-Mfa1 antibodies on infection and periodontitis was previously unknown. In this study, we report for the first time that anti-Mfa1 monoclonal antibodies can reduce infection and improve periodontitis. These findings suggest that Mfa1 represents a promising therapeutic target, and the development of anti-Mfa1 mAbs holds a potential as essential diagnostic and adjunctive therapeutic tools for managing -related diseases.
()是一种革兰氏阴性、产黑色素的厌氧菌,是牙周炎的主要病原体和主要病因。菌毛蛋白Mfa1是()的关键毒力因子,在细菌粘附、定植、生物膜形成和持续性炎症中起关键作用,使其成为一个有前景的治疗靶点。然而,抗Mfa1抗体的作用及潜在的保护机制在很大程度上仍未被探索。在此,我们开发并鉴定了靶向()Mfa1蛋白的单克隆抗体(mAb)。功能分析表明,抗Mfa1 mAb介导细菌凝集,并抑制()对唾液包被的羟基磷灰石和宿主细胞的粘附。值得注意的是,抗Mfa1 mAb在()诱导的实验性牙周炎模型中显著降低了细菌负荷和牙槽骨丧失。这些结果表明,抗Mfa1 mAb有助于减轻()感染,并为开发针对Mfa1的治疗药物的适当辅助治疗方案提供了重要见解。
菌毛(纤毛)在细菌粘附、宿主细胞和组织的侵袭以及生物膜形成中起重要作用。研究表明,()的两种菌毛FimA和Mfa1通过与宿主组织和其他细菌结合,对定植和感染很重要。虽然抗FimA抗体已被证明可改善牙周炎,但抗Mfa1抗体对()感染和牙周炎的影响此前尚不清楚。在本研究中,我们首次报道抗Mfa1单克隆抗体可减少()感染并改善牙周炎。这些发现表明,Mfa1是一个有前景的治疗靶点,抗Mfa1 mAb的开发有望成为管理与()相关疾病的重要诊断和辅助治疗工具。