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Toxin-Deficient Mutants of Bacillus anthracis Are Lethal in a Murine Model for Pulmonary Anthrax

机译:炭疽杆菌毒素缺乏突变体在肺炭疽鼠模型中具有致死性。

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Bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. The capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. We show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to those of the parent strain. Mutants lacking one or more of the structural genes for the toxin proteins, i.e., protective antigen, lethal factor, and edema factor, disseminated from the lung to the spleen at rates similar to that of the virulent parental strain. The 50% lethal dose (LD50) and mean time to death (MTD) of the mutants did not differ significantly from those of the parent. The LD50s or MTDs were also unaffected relative to those of the parent strain when mice were inoculated intravenously with vegetative cells. Nonetheless, histopathological examination of tissues revealed subtle but distinct differences in infections by the parent compared to some toxin mutants, suggesting that the host response is affected by toxin proteins synthesized during infection.
机译:炭疽杆菌的病原体 Bacillus anthracis 产生至少三种主要毒力因子:致命毒素,浮肿毒素和胶囊。在小鼠吸入性炭疽的传播和致死性方面,胶囊绝对是必需的,但毒素在感染过程中的作用尚不清楚。我们在鼠模型中显示,当特定毒素无效突变体的孢子被引入肺部时,其传播和致死性与亲本菌株相当。缺乏一种或多种毒素蛋白结构基因的突变体,即保护性抗原,致死因子和浮肿因子,以与有毒的亲代菌株相似的速率从肺中扩散到脾脏。突变体的50%致死剂量(LD 50 )和平均致死时间(MTD)与亲本无明显差异。相对于亲本菌株的LD 50 s或MTDs,在给小鼠静脉内接种营养细胞后也没有受到影响。尽管如此,组织的组织病理学检查显示,与某些毒素突变体相比,亲本的感染有细微但明显的差异,这表明宿主反应受到感染过程中合成的毒素蛋白的影响。

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