Background

The rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin utilization A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii.

Methods

Recombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii, and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice.

Results

Specific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii-induced damage upon administration of the two immunogens.

Conclusions

The combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains.

中文翻译：

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增强对鲍曼不动杆菌感染的免疫保护：Bap 和 BauA 在小鼠模型中的协同作用

背景

多重耐药鲍曼不动杆菌的兴起对医院环境构成严重威胁，导致死亡率上升并引起全球关注。生物膜相关蛋白 (Bap) 促进的生物膜形成和鲍曼不动杆菌素利用 A (BauA) 介导的铁吸收能力有助于多重耐药菌株的持久性和存活。在本研究中，我们旨在研究同时破坏 BauA 和 Bap 功能作为控制鲍曼不动杆菌的策略的潜力。

方法

表达、纯化重组 Bap 和 BauA，并单独或联合皮下给予 BALB/c 小鼠。随后，对小鼠进行腹膜内鲍曼不动杆菌攻击，并评估脾、肺和肝脏中的细菌负荷和组织损伤。评估血清样本以确定存活小鼠的抗体滴度。

结果

特异性IgG抗体显着升高。与单独的 BauA 或 Bap 相比，抗原的组合导致特异性 IgG 的滴度增强。抗体在七个月内保持稳定。与单独给药相比，Bap 和 BauA 的组合对鲍曼不动杆菌感染表现出优异的免疫保护作用，从而进一步减少了肝脏、脾脏和肺部的细菌负荷。组织病理学分析表明，施用两种免疫原后，可以成功保护组织免受鲍曼不动杆菌诱导的损伤。

结论

Bap 和 BauA 的组合有可能针对更广泛的鲍曼不动杆菌菌株，包括表达 Bap 或 BauA 的菌株，从而提高其针对多种菌株的功效。