Steinman L, Weiss A, Adelman N, Lim M, Zuniga R, Oehlert J, Hewlett E, Falkow S
Proc Natl Acad Sci U S A. 1985 Dec;82(24):8733-6. doi: 10.1073/pnas.82.24.8733.
A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.
一种由百日咳免疫诱导的脑病小鼠模型已被描述；它具有一些与某些严重反应极为相似的特征，包括癫痫发作以及类似休克的状态并导致死亡，这些严重反应在接种百日咳博德特氏菌（百日咳）疫苗后偶尔会出现。对脑病的易感性与主要组织相容性复合体的基因相关，并且也与对牛血清白蛋白抗体反应水平的遗传调控有关。在本研究中，我们调查了哪种细菌决定因素导致了脑病。有两条证据表明百日咳毒素是活性细菌成分。对具有单个受影响毒力因子的百日咳博德特氏菌单点突变体进行了测试。产生缺陷型百日咳毒素的突变体诱导脑病的能力大大降低，而缺乏溶血素和腺苷酸环化酶的无毒突变体在小鼠模型中的活性与有毒菌株相同。对纯化的百日咳毒素加牛血清白蛋白进行了测试，发现其可诱导致命性脑病，这表明该毒素是百日咳博德特氏菌中导致脑病的关键成分。
