Department of Biology, Shahed University, Tehran, Iran.
Applied Microbiology Research Center, Systems biology and poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Immunol Lett. 2023 Oct;262:18-26. doi: 10.1016/j.imlet.2023.08.004. Epub 2023 Aug 29.
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.
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.
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.
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.
多重耐药鲍曼不动杆菌的出现对医院环境构成了严重威胁，导致死亡率上升，并引起了全球关注。生物膜相关蛋白（Bap）促进生物膜的形成，鲍曼不动杆菌利用铁的能力由鲍曼不动杆菌利用铁的 A（BauA）介导，这有助于多药耐药株的持续存在和生存。在这项研究中，我们旨在研究同时破坏 BauA 和 Bap 功能的潜力，作为控制鲍曼不动杆菌的一种策略。
重组 Bap 和 BauA 被表达、纯化，并分别和联合皮下给予 BALB/c 小鼠。随后，用鲍曼不动杆菌对小鼠进行腹腔内攻击，并评估脾脏、肺和肝脏中的细菌负荷和组织损伤。评估存活小鼠的血清样本以确定抗体滴度。
特异性 IgG 抗体显著增加。与 BauA 或 Bap 单独相比，抗原的组合导致特异性 IgGs 的滴度增加。抗体在七个月的时间内保持稳定。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更好的免疫保护作用，导致肝脏、脾脏和肺部的细菌负荷进一步降低。组织病理学分析表明，两种免疫原给药后，组织成功地免受鲍曼不动杆菌诱导的损伤。
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，从而提高其对多种菌株的疗效。
