Sawa T, Ohara M, Kurahashi K, Twining S S, Frank D W, Doroques D B, Long T, Gropper M A, Wiener-Kronish J P
Departments of Anesthesia and Medicine, Cardiovascular Research Institute, The University of California, San Francisco, California 94143, USA.
Infect Immun. 1998 Jul;66(7):3242-9. doi: 10.1128/IAI.66.7.3242-3249.1998.
The role of quorum sensing by Pseudomonas aeruginosa in producing cytotoxicity has not been fully investigated. Strains of P. aeruginosa have been characterized as having an invasive or a cytotoxic phenotype (S. M. J. Fleiszig et al., Infect. Immun. 65:579-586, 1997). We noted that the application of a large inoculum of the invasive strain 6294 caused cytotoxicity of cultured epithelial cells. To investigate this dose-related cytotoxicity, we compared the behavior of 6294 to that of another invasive strain, PAO1, and determined whether the cytotoxicity could be related to quorum sensing. Both invasive strains, 6294 and PAO1, appear to have quorum-sensing systems that were operative when large doses of bacteria were applied to cultured lung epithelial cells or instilled into the lungs of animals. Nonetheless, only 6294 was cytotoxic. Cytotoxicity induced by 6294 correlated with increased elastase production. These experiments suggest that there are multiple mechanisms for the induction of cytotoxicity, pathology, and mortality in vivo. However, in vivo cytotoxicity and mortality, but not pathology, could be predicted by quantitative in vitro cellular damage experiments utilizing a range of bacteria-to-cell ratios. It appears that quorum sensing may inversely correlate with virulence in that strains that produced PAI [N-(3-oxododecanoyl) homoserine lactone] also appeared to attract more polymorphonuclear leukocytes in vivo and were possibly eliminated more quickly. In addition, exoproduct production in bacteriological medium in vitro may differ significantly from exoproduct expression from infections in vivo or during cocultivation of bacteria with tissue culture cells.
铜绿假单胞菌群体感应在产生细胞毒性方面的作用尚未得到充分研究。铜绿假单胞菌菌株已被鉴定为具有侵袭性或细胞毒性表型（S.M.J.弗莱西格等人，《感染与免疫》65:579 - 586，1997年）。我们注意到，接种大量侵袭性菌株6294会导致培养的上皮细胞产生细胞毒性。为了研究这种剂量相关的细胞毒性，我们将6294的行为与另一种侵袭性菌株PAO1的行为进行了比较，并确定细胞毒性是否与群体感应有关。当将大量细菌应用于培养的肺上皮细胞或注入动物肺部时，侵袭性菌株6294和PAO1似乎都具有可运作的群体感应系统。尽管如此，只有6294具有细胞毒性。6294诱导的细胞毒性与弹性蛋白酶产量增加相关。这些实验表明，体内诱导细胞毒性、病理变化和死亡率存在多种机制。然而，利用一系列细菌与细胞比例进行的定量体外细胞损伤实验可以预测体内细胞毒性和死亡率，但不能预测病理变化。群体感应似乎可能与毒力呈负相关，因为产生PAI[N -（3 - 氧代十二烷酰基）高丝氨酸内酯]的菌株在体内似乎也吸引了更多的多形核白细胞，并且可能被更快地清除。此外，体外细菌培养基中的外产物产生可能与体内感染或细菌与组织培养细胞共培养期间的外产物表达有显著差异。
