Woods D E, Cryz S J, Friedman R L, Iglewski B H
Infect Immun. 1982 Jun;36(3):1223-8. doi: 10.1128/iai.36.3.1223-1228.1982.
A chronic pulmonary infection model in rats was employed to assess the role of individual Pseudomonas aeruginosa exoproducts in disease due to this organism. Groups of rats were inoculated transtracheally with agar beads in which were embedded approximately 10(4) colony-forming units of P. aerugijnosa PAO and the PAO derivatives PR1, T1, E64, and a mixture of T1 and E64 in equal numbers (10(4)). Eight animals from each group were sacrificed at 3, 9, and 30 days after challenge, and their lungs were examined for histopathological changes, bacterial numbers, and the presence of P. aeruginosa exoproducts. The Tox- mutant T1 and the PR1 mutant, which produces enzymatically inactive toxin A, were both found to be less virulent in the rat lung model than was the toxigenic parental strain PAO. Pathological changes seen in animals infected with these mutants were restricted to intra- and peribronchial inflammation, whereas the toxigenic parental strain caused parenchymal changes, including a dense mononuclear-cell infiltration in the alveolar spaces in addition to intra- and peribronchial inflammation. Additionally, mutant E64, which produces a temperature-sensitive elastase, was also found to be less virulent in the rat lung model than was the parental strain. These data demonstrate that both active toxin A and elastase are required for maximum virulence of P. aeruginosa in this model.
采用大鼠慢性肺部感染模型来评估铜绿假单胞菌各外毒素产物在该菌所致疾病中的作用。将大鼠分组，经气管接种含有约10⁴个铜绿假单胞菌PAO及PAO衍生物PR1、T1、E64的琼脂珠，以及等量（10⁴）的T1和E64混合物。在攻毒后3天、9天和30天，每组处死8只动物，检查其肺部的组织病理学变化、细菌数量以及铜绿假单胞菌外毒素产物的存在情况。发现产生无酶活性毒素A的Tox⁻突变体T1和PR1突变体在大鼠肺部模型中的毒力均低于产毒亲代菌株PAO。感染这些突变体的动物所出现的病理变化仅限于支气管内和支气管周围炎症，而产毒亲代菌株则引起实质变化，除支气管内和支气管周围炎症外，还包括肺泡腔内密集的单核细胞浸润。此外，发现产生温度敏感型弹性蛋白酶的突变体E64在大鼠肺部模型中的毒力也低于亲代菌株。这些数据表明，在该模型中，活性毒素A和弹性蛋白酶都是铜绿假单胞菌发挥最大毒力所必需的。
