McArthur Jason D, West Nicholas P, Cole Jason N, Jungnitz Heidrun, Guzmán Carlos A, Chin James, Lehrbach Philip R, Djordjevic Steven P, Walker Mark J
Department of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
FEMS Microbiol Lett. 2003 Apr 11;221(1):7-16. doi: 10.1016/S0378-1097(03)00162-9.
We have constructed an aromatic amino acid auxotrophic mutant of Bordetella bronchiseptica, harbouring mutations in aroA and trpE to investigate the use of such a strain as a live-attenuated vaccine. B. bronchiseptica aroA trpE was unable to grow in minimal medium without aromatic supplementation. Compared to the parental wild-type strain, the mutant displayed significantly reduced abilities to invade and survive within the mouse macrophage-like cell line J774A.1 in vitro and in the murine respiratory tract following experimental intranasal infection. Mice vaccinated with B. bronchiseptica aroA trpE displayed significant dose-dependent increases in B. bronchiseptica-specific antibody responses, and exhibited increases in the number of B. bronchiseptica-reactive spleen cells in lymphoproliferation assays. Immunised animals were protected against lung colonisation after challenge with the wild-type parental strain. With such a broad host range displayed by B. bronchiseptica, the attenuated strain constructed in this study may not only be used for the prevention of B. bronchiseptica-associated disease, but also for the potential delivery of heterologous antigen.
我们构建了支气管败血波氏杆菌的芳香族氨基酸营养缺陷型突变体,该突变体在aroA和trpE基因上存在突变,以研究这种菌株作为减毒活疫苗的用途。支气管败血波氏杆菌aroA trpE突变体在不添加芳香族氨基酸的基本培养基中无法生长。与亲本野生型菌株相比,该突变体在体外以及实验性鼻内感染后的小鼠呼吸道中,在小鼠巨噬细胞样细胞系J774A.1内侵袭和存活的能力显著降低。用支气管败血波氏杆菌aroA trpE疫苗接种的小鼠,其支气管败血波氏杆菌特异性抗体反应呈显著的剂量依赖性增加,并且在淋巴细胞增殖试验中,支气管败血波氏杆菌反应性脾细胞数量增加。免疫动物在用野生型亲本菌株攻击后可免受肺部定植。鉴于支气管败血波氏杆菌具有如此广泛的宿主范围,本研究构建的减毒株不仅可用于预防支气管败血波氏杆菌相关疾病,还可用于潜在的异源抗原递送。