金黄色葡萄球菌凝集因子A单克隆抗体的抑制活性研究。

IF 4.7 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-10-08 Epub Date: 2025-09-08 DOI:10.1128/mbio.02197-25
Biswarup Banerjee, Carla Emolo, Miaomiao Shi, Abrar Abdullah Al Fardan, Tonu Pius, Muhammad Shafiul Azam, Molly McAdow, Olaf Schneewind, Dominique Missiakas
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引用次数: 0

摘要

金黄色葡萄球菌感染是人类败血症的常见原因,是一种死亡率高且无特异性干预的疾病。在侵袭性疾病中,细菌表面显示的聚集因子A (ClfA)在促进金黄色葡萄球菌复制中起关键作用。几十年的研究已经指出了ClfA参与的一系列广泛的配体。这些相互作用的总和支持这种病原体在血液中生存和复制的独特能力。其中一种配体是纤维蛋白。ClfA作为金黄色葡萄球菌的关键凝集因子,促进纤维蛋白电缆中细菌的屏蔽和它们从吞噬细胞的物理逃逸。在这里,我们比较了小鼠免疫后引发的一系列针对ClfA配体结合域的单克隆抗体。我们分析这些抗体的能力,以中和ClfA相互作用和促进葡萄球菌在全血中的摄取。我们发现,虽然所有抗体都促进了调理吞噬细胞的摄取,但只有那些也抑制ClfA与配体相互作用的抗体才能减少金黄色葡萄球菌血流攻击后动物的细菌负担。以抗体为基础的对抗细菌病原体的方法已经模拟了产生毒素或被包裹的病原体,其相关保护可以减少到使用组织培养细胞测量抗体中和或补体固定活性。这些方法对金黄色葡萄球菌无效,增加了抗体价值的不确定性。在这里,我们使用一系列针对凝集因子a的小鼠单克隆抗体,这是一种允许金黄色葡萄球菌在血液中茁壮成长的表面蛋白,以查询如何利用抗体来对抗具有强大毒力因子的病原体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibitory activities of monoclonal antibodies against Staphylococcus aureus clumping factor A.

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. Clumping factor A (ClfA) displayed on the bacterial surface plays a key role in promoting S. aureus replication during invasive disease. Decades of research have pointed to a wide array of ligands engaged by ClfA. The sum of these interactions supports the unique ability of this pathogen to survive and replicate in the blood stream. One such ligand is fibrin. ClfA acts as the key agglutinating factor of S. aureus by promoting the shielding of bacteria in fibrin cables and their physical escape from phagocytes. Here, we compare a series of monoclonal antibodies elicited against the ligand binding domain of ClfA following immunization of mice. We analyze these antibodies for their ability to neutralize ClfA interactions and to promote the uptake of staphylococci in whole blood. We find that while all the antibodies promoted opsonophagocytic uptake, only those that also inhibited ClfA interactions with ligands reduced bacterial burdens in animals following blood stream challenge with S. aureus.IMPORTANCEAntibody-based approaches to fight bacterial pathogens have been modeled on toxin-producing or encapsulated pathogens for which correlates of protection can be reduced to measuring antibody neutralization or complement-fixing activities using tissue-cultured cells. Such approaches have failed against Staphylococcus aureus raising uncertainty about the value of antibodies. Here, we use a series of mouse monoclonal antibodies directed against clumping factor A, a surface protein that allows S. aureus to thrive in the blood stream, to query how antibodies may be exploited against a pathogen endowed with a formidable array of virulence factors.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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