Welkos S L, Friedlander A M
Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701-5011.
Microb Pathog. 1988 Jan;4(1):53-69. doi: 10.1016/0882-4010(88)90048-4.
The pathogenesis of lethal infection by the nonecapsulated, toxigenic Sterne strain of Bacillus anthracis and the genetic basis of resistance were characterized in mice. Lethal doses of Sterne spores produced disease in susceptible mice similar to that caused by toxigenic and encapsulated B. anthracis. At the inoculation site, the mice developed an edematous exudate with large concentrations of bacilli and toxin. In the susceptible A/J strain, lethal infection was accompanied by systemic invasion and serum anthrax toxin levels increased in parallel with systemic bacterial concentrations and with the mortality rate. Host resistance to Sterne infection was associated with the ability to synthesize the complement component 5 (C5). All Sterne-resistant mouse strains had a functional gene (Hc) encoding C5, whereas susceptible mice were deficient in C5. A/J mice could be passively protected from lethal challenge by C5-positive serum but not by serum from C5-negative congenic mice. Also resistance was linked to production of C5 in individual backcross (97%) and F2 (98%) mice. The distribution pattern for recombinant inbred mice was consistent with a major role in host resistance of Hc or a closely linked locus, although other genes probably contribute. This mouse model will be useful in characterizing the pathogenesis of anthrax and testing the safety and efficacy of new anthrax vaccines.
对小鼠体内无荚膜、产毒素的炭疽芽孢杆菌Sterne菌株致死性感染的发病机制及抗性的遗传基础进行了研究。致死剂量的Sterne芽孢在易感小鼠中引发的疾病与产毒素的有荚膜炭疽芽孢杆菌所引起的疾病相似。在接种部位，小鼠出现水肿性渗出物，其中含有大量杆菌和毒素。在易感的A/J品系中，致死性感染伴随着全身侵袭，血清炭疽毒素水平与全身细菌浓度及死亡率平行升高。宿主对Sterne感染的抗性与合成补体成分5（C5）的能力有关。所有抗Sterne感染的小鼠品系都有一个编码C5的功能性基因（Hc），而易感小鼠缺乏C5。A/J小鼠可通过C5阳性血清被动保护免受致死性攻击，但不能通过C5阴性同基因小鼠的血清获得保护。此外，抗性与单个回交（97%）和F2（98%）小鼠中C5的产生有关。重组近交系小鼠的分布模式与Hc或紧密连锁基因座在宿主抗性中起主要作用一致，尽管可能还有其他基因起作用。这个小鼠模型将有助于阐明炭疽的发病机制，并测试新型炭疽疫苗的安全性和有效性。
