Geers T A, Baker N R
J Antimicrob Chemother. 1987 May;19(5):569-78. doi: 10.1093/jac/19.5.569.
Hamster tracheal organ cultures were used to evaluate the ability of two aminoglycoside and two beta-lactam antibiotics to protect the epithelium from damage due to Pseudomonas aeruginosa infection. Hamster tracheal explants were infected with strains of P. aeruginosa for 4 h and washed to remove nonadherent organisms. The explants were incubated for an additional 18 h in fresh minimal essential medium containing inhibitory or subinhibitory concentrations of antibiotics. The explants were examined by scanning electron microscopy and bacterial elastase and exotoxin A production was detected by ELISA and a western blot assay respectively. Concentrations of aminoglycosides below the MIC for the infecting strain protected the epithelium from damage and inhibited the production of exotoxin and elastase. The beta-lactam antibiotics were not protective and epithelial damage was observed at antibiotic levels equal to or higher than the MIC for that strain. The beta-lactam treated cultures continued to release elastase and exotoxin A at antibiotic concentrations equivalent to or higher than the MIC for that strain. Thus subinhibitory levels of aminoglycoside antibiotics could protect the infected epithelium from damage by inhibiting the release of toxic substances from the invading bacteria. In contrast, bacteria exposed to beta-lactam antibiotics may continue to release extracellular toxins which can damage the tissue.
采用仓鼠气管器官培养法评估两种氨基糖苷类抗生素和两种β-内酰胺类抗生素保护上皮细胞免受铜绿假单胞菌感染损伤的能力。将仓鼠气管外植体用铜绿假单胞菌菌株感染4小时，然后冲洗以去除未黏附的细菌。将外植体在含有抑制性或亚抑制性浓度抗生素的新鲜最低限度基本培养基中再孵育18小时。通过扫描电子显微镜检查外植体，并分别通过酶联免疫吸附测定法（ELISA）和蛋白质印迹法检测细菌弹性蛋白酶和外毒素A的产生。低于感染菌株最低抑菌浓度（MIC）的氨基糖苷类抗生素浓度可保护上皮细胞免受损伤，并抑制外毒素和弹性蛋白酶的产生。β-内酰胺类抗生素没有保护作用，在等于或高于该菌株MIC的抗生素水平下观察到上皮损伤。用β-内酰胺类抗生素处理的培养物在等于或高于该菌株MIC的抗生素浓度下继续释放弹性蛋白酶和外毒素A。因此，亚抑制水平的氨基糖苷类抗生素可通过抑制入侵细菌释放有毒物质来保护受感染的上皮细胞免受损伤。相比之下，暴露于β-内酰胺类抗生素的细菌可能会继续释放可损伤组织的细胞外毒素。
