Zimmerman Shawn M, Dyke Jeremy S, Jelesijevic Tomislav P, Michel Frank, Lafontaine Eric R, Hogan Robert J
Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
Infect Immun. 2017 Jul 19;85(8). doi: 10.1128/IAI.00102-17. Print 2017 Aug.
, a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. The organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic Gram-negative bacteria. In the present study, we investigated one of these autotransporters, BatA, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed , elicits production of antibodies during infection, and contributes to pathogenicity in a mouse aerosol challenge model. A mutation in the gene of wild-type strain ATCC 23344 was found to be particularly attenuating, as BALB/c mice infected with the equivalent of 80 median lethal doses cleared the organism. This finding prompted us to test the hypothesis that vaccination with the mutant strain elicits protective immunity against subsequent infection with wild-type bacteria. We discovered that not only does vaccination provide high levels of protection against lethal aerosol challenge with ATCC 23344, it also protects against infection with multiple isolates of the closely related organism and causative agent of melioidosis, Passive-transfer experiments also revealed that the protective immunity afforded by vaccination with the mutant strain is predominantly mediated by IgG antibodies binding to antigens expressed exclusively Collectively, our data demonstrate that BatA is a target for developing medical countermeasures and that vaccination with a mutant lacking expression of the protein provides a platform to gain insights regarding mechanisms of protective immunity against and , including antigen discovery.
鼻疽杆菌是一种兼性胞内细菌，属于一级生物威胁因子，可引发致命的人畜共患病鼻疽。该生物体拥有多个编码自转运蛋白的基因，这些蛋白是重要的毒力因子，也是开发针对革兰氏阴性病原菌对策的靶点。在本研究中，我们对其中一种自转运蛋白BatA进行了研究，结果表明它具有脂解活性，有助于在细胞内存活，在感染过程中表达，能引发抗体产生，并在小鼠气溶胶攻击模型中对致病性有影响。野生型菌株ATCC 23344的该基因发生突变后毒力显著减弱，因为感染相当于80个半数致死剂量的BALB/c小鼠能够清除该生物体。这一发现促使我们检验以下假设：用该突变株进行疫苗接种可引发针对随后野生型细菌感染的保护性免疫。我们发现，疫苗接种不仅能提供高水平的保护，抵御ATCC 23344的致命气溶胶攻击，还能预防感染密切相关生物体的多个分离株以及类鼻疽病的病原体。被动转移实验还表明，用该突变株进行疫苗接种所提供的保护性免疫主要由与仅在……表达的抗原结合的IgG抗体介导。总体而言，我们的数据表明BatA是开发医学对策的一个靶点，用缺乏该蛋白表达的突变株进行疫苗接种提供了一个平台，有助于深入了解针对鼻疽杆菌和类鼻疽杆菌的保护性免疫机制，包括抗原发现。
