不同品系小鼠对炭疽芽胞杆菌弱毒株芽胞的敏感性研究

通过比较四种品系小鼠对炭疽芽胞杆菌（Bacillus anthracis）（简称炭疽杆菌）弱毒株芽胞的敏感性，确定炭疽杆菌弱毒株芽胞攻毒合适的动物模型。采用炭疽杆菌弱毒株A16Q1（pXO1-、pXO2+）和A16PI2（pXO1+、pXO2-）的芽胞对四种品系小鼠（DBA/2、KM、ICR和BALB/c）进行腹腔攻毒，记录小鼠死亡时间，计算LD₅₀、绘制存活曲线并统计分析。运用较敏感的KM小鼠研究不同canSNP基因型毒素缺陷株（含pXO2拷贝数不同）芽胞的毒力差异。利用更为敏感的DBA/2小鼠评价S-层蛋白BA3338对荚膜缺陷株芽胞毒力的影响。结果表明，在四种品系小鼠中，毒素缺陷株芽胞的毒力均高于荚膜缺陷株芽胞的毒力。DBA/2小鼠对炭疽杆菌弱毒株芽胞的剂量依赖关系最好，最为敏感，其次是KM小鼠，而ICR小鼠和BALB/c小鼠对炭疽杆菌弱毒株芽胞不敏感。确定了DBA/2小鼠和KM小鼠在炭疽杆菌弱毒株芽胞研究中的适用性。使用KM小鼠评价了不同canSNP基因型炭疽杆菌芽胞的毒力差异，结果表明，不同canSNP基因型炭疽杆菌由于所含pXO2质粒拷贝数的差异导致芽胞的毒力不同。使用DBA/2小鼠评价了S-层蛋白BA3338缺失对炭疽杆菌芽胞毒力的影响，表明BA3338基因的缺失导致炭疽杆菌芽胞毒力降低。

Susceptibilities of Different Mice Strains to the Attenuated Spores Bacillus anthracis

This study aims to compare the susceptibility of four mice strains to the attenuated spores of Bacillus anthracis, and determine a suitable animal model for the attenuated spore challenge. The spores of two B. anthracis attenuated strains A16Q1 (pXO1-, pXO2+) and A16PI2 (pXO1+, pXO2-) were used to challenge four mice strains (DBA/2, KM, ICR and BALB/c) by intraperitoneal injection, and the times of mice death were recorded. Then, completed to statistical analysis, calculated LD₅₀, and drew survival curve. Relatively sensitive KM mice were used to study the virulence difference of different canSNP genotypes encapsulated and toxin auxotrophs spores (harboring different copy of pXO2). More sensitive DBA/2 mice were used to evaluate the effect of S-layer protein BA3338 on the virulence of the capsule-deficient spores. The results showed that the virulence of encapsulated and toxin auxotrophs B. anthracis spores were stronger than those of nonencapsulated toxin-producing strains for those four mice strains. DBA/2 mice had the best dose-dependent relationship to the B. anthracis attenuated spores and were the most sensitive, followed by KM mice, whereas ICR and BALB/c were quite insensitive to challenge. In this study, the applicability of DBA/2 mice and KM mice in the study of B. anthracis attenuated spores were determined. Using KM mice that are sensitive to encapsulated strain to evaluate the virulence difference of different canSNP genotypes. The results indicated that different canSNP genotypic B. anthracis containing the difference of pXO2 plasmid copy number conduced to different virulence of spore. DBA/2 mice were used to evaluate the effect of the S-layer protein BA3338 defect on the virulence of B. anthracis, indicated that the defect of BA3338 gene may lead to a decline in the virulence of B. anthracis.