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鲍曼不动杆菌 BamA 重组蛋白的交叉反应性和免疫治疗潜力。

Cross-reactivity and immunotherapeutic potential of BamA recombinant protein from Acinetobacter baumannii.

机构信息

Bio-Manguinhos, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Rio de Janeiro, RJ, Brazil; Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Rio de Janeiro, RJ, Brazil.

Bio-Manguinhos, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Rio de Janeiro, RJ, Brazil.

出版信息

Microbes Infect. 2021 May-Jun;23(4-5):104801. doi: 10.1016/j.micinf.2021.104801. Epub 2021 Feb 11.

Abstract

Acinetobacter baumannii is an important nosocomial pathogen. BamA is a protein that belongs to a complex responsible for organizing the proteins on the bacterial outer membrane. In this work, we aimed to evaluate murine immune responses to BamA recombinant protein (rAbBamA) from A. baumannii in an animal model of infection, and to assess cross-reactivity of this target for the development of anti-A. baumannii vaccines or diagnostics. Immunization of mice with rAbBamA elicited high antibody titers and antibody recognition of native A. baumannii BamA. Immunofluorescence also detected binding to the bacterial surface. After challenge, immunized mice demonstrated a 40% survival increase and better bacterial clearance in kidneys. Immunoblot of anti-rAbBamA against other medically relevant bacteria showed binding to proteins of approximately 35 kDa in Klebsiella pneumoniae and Escherichia coli lysates, primarily identified as OmpA and OmpC, respectively. Altogether, our data show that anti-rAbBamA antibodies provide a protective response against A. baumannii infection in mice. However, the response elicited by immunization with rAbBamA is not completely specific to A. baumannii. Although a broad-spectrum vaccine that protects against various pathogens is an appealing strategy, antibody reactivity against the human microbiota is undesired. In fact, immunization with rAbBamA produced noticeable effects on the gut microbiota. However, the changes elicited were small and non-specific, given that no significant changes in the abundance of Proteobacteria were observed. Overall, rAbBamA is a promising target, but specificity must be considered in the development of immunological tools against A. baumannii.

摘要

鲍曼不动杆菌是一种重要的医院获得性病原体。BamA 是一种蛋白质,属于负责组织细菌外膜上蛋白质的复合物。在这项工作中,我们旨在评估鲍曼不动杆菌 BamA 重组蛋白(rAbBamA)在感染动物模型中的鼠免疫反应,并评估该靶标对开发抗鲍曼不动杆菌疫苗或诊断方法的交叉反应性。用 rAbBamA 免疫小鼠可引起高抗体滴度和对天然鲍曼不动杆菌 BamA 的抗体识别。免疫荧光还检测到与细菌表面的结合。在挑战后,免疫小鼠的存活率增加了 40%,肾脏中的细菌清除率更好。抗 rAbBamA 的免疫印迹显示与肺炎克雷伯菌和大肠杆菌裂解物中的约 35 kDa 蛋白结合,分别主要鉴定为 OmpA 和 OmpC。总之,我们的数据表明,抗 rAbBamA 抗体可提供针对小鼠鲍曼不动杆菌感染的保护反应。然而,用 rAbBamA 免疫引起的反应并非完全特异于鲍曼不动杆菌。尽管针对各种病原体的广谱疫苗是一种有吸引力的策略,但针对人类微生物群的抗体反应是不理想的。事实上,用 rAbBamA 免疫会对肠道微生物群产生明显影响。然而,所引起的变化很小且非特异性,因为没有观察到变形菌门丰度的显著变化。总的来说,rAbBamA 是一个有前途的靶标,但在开发针对鲍曼不动杆菌的免疫工具时必须考虑特异性。

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