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评估三聚体自转运蛋白 Ata 作为治疗鲍曼不动杆菌感染的疫苗候选物。

Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections.

机构信息

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Infect Immun. 2012 Oct;80(10):3381-8. doi: 10.1128/IAI.06096-11. Epub 2012 Jul 23.

Abstract

Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of A. baumannii, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of A. baumannii to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against A. baumannii ATCC 17978 and showed low to moderate killing activity against four heterologous A. baumannii strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested A. baumannii isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of A. baumannii ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections.

摘要

鲍曼不动杆菌是一种多药耐药(MDR)的医院获得性病原体,需要免疫治疗的替代方法。我们之前鉴定了鲍曼不动杆菌的一种表面自转运蛋白 Ata,它与多种细胞外基质/基底膜蛋白结合,是完全毒力、生物膜形成和鲍曼不动杆菌与 IV 型胶原蛋白黏附所必需的。我们在这里显示 Ata 与 IV 型胶原蛋白的结合被针对 Ata 的抗体所抑制。此外,在补体和多形核细胞(PMN)存在的情况下,针对 Ata 的抗体对 ATCC 17978 型鲍曼不动杆菌具有高度调理作用,并对四种异源鲍曼不动杆菌菌株表现出低至中度杀伤活性,而在没有 PMN 的情况下,针对 Ata 的抗体有效地促进了所有测试的鲍曼不动杆菌分离株的补体依赖性杀菌杀伤。在免疫功能正常和免疫功能低下的小鼠肺炎感染模型中,我们发现与正常兔血清相比,针对 Ata 的抗血清显著降低了感染小鼠肺部 ATCC 17978 型和两种 MDR 菌株的水平。Ata 产生抗黏附、杀菌、调理吞噬和保护抗体的能力验证了其作为针对 MDR 鲍曼不动杆菌感染的抗原靶标的潜在用途。

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