Woods D E, Lam J S, Paranchych W, Speert D P, Campbell M, Godfrey A J
Department of Microbiology and Infectious Diseases, University of Calgary, Canada.
Can J Microbiol. 1997 Jun;43(6):541-51. doi: 10.1139/m97-077.
The potential pathogenicity of a microorganism is a major concern for Health Canada evaluators, who will be processing new biotechnology products under the Canadian Environmental Protection Act. Potential pathogenicity is generally predicted by the results of animal pathogenicity studies. In an attempt to define surrogate data for an animal model, this study was initiated. Pseudomonas aeruginosa isolates from clinical and environmental sources were screened for their pilus type, serotype, lipopolysaccharide type, ability to evade host responses, and production of toxin A, exoenzyme S, elastase, phospholipase C, and total protease. The 50% lethal dose (LD50) of the same isolates was determined in the neutropenic mouse model of infection. An attempted correlation was drawn between each (or combinations) of the virulence determinants and the LD50. Stepwise linear regression showed that the presence of high levels of exoenzyme S in association with elastase or phospholipase C, or to a minor extent toxin A, was correlated with low numbers of bacteria required to elicit an LD50. No correlation between any of the other factors examined and virulence was detected. The data suggest that an in vitro high level of exoenzyme S production could be used as surrogate information for neutropenic mouse modelling; however, the levels of all of the extracellular enzymes should be considered when making such an assessment.
微生物的潜在致病性是加拿大卫生部评估人员主要关注的问题，他们将根据《加拿大环境保护法》对新的生物技术产品进行评估。潜在致病性通常通过动物致病性研究的结果来预测。为了确定动物模型的替代数据，开展了本研究。对从临床和环境来源分离出的铜绿假单胞菌进行筛选，检测其菌毛类型、血清型、脂多糖类型、逃避宿主反应的能力以及毒素A、外毒素S、弹性蛋白酶、磷脂酶C和总蛋白酶的产生情况。在中性粒细胞减少的小鼠感染模型中测定相同分离株的50%致死剂量（LD50）。尝试在每个毒力决定因素（或其组合）与LD50之间建立相关性。逐步线性回归表明，高水平的外毒素S与弹性蛋白酶或磷脂酶C同时存在，或在较小程度上与毒素A同时存在，与引发LD50所需的细菌数量少相关。未检测到所检查的任何其他因素与毒力之间存在相关性。数据表明，体外高水平产生外毒素S可作为中性粒细胞减少小鼠建模的替代信息；然而，在进行此类评估时应考虑所有细胞外酶的水平。
