2012年12月2日 讯 /生物谷BIOON/ --近日，刊登在国际杂志Antimicrobial Agents and Chemotherapy上刊登的一篇研究报告“Efficacy of Liposomal Bismuth-Ethanedithiol Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection”中，来自劳伦森大学的研究者揭示了装有妥布霉素的铋-乙二硫醇脂质体治疗绿脓杆菌感染的小鼠的疗效。
在本项研究中，研究者Abdelwahab Omri说，我们目的是想要研究当铋-乙二硫醇混合物加入到装载有妥布霉素的脂质体（LipoBiEDT-TOB）中，其对于绿脓杆菌群体感应信号分子N-酰基高丝氨酸内酯以及毒力因子释放的影响和作用。
其中N-酰基高丝氨酸内酯信号分子可以由生物传感器来进行监测，细菌毒力因子的释放可以由分光光度计进行测量评估。受细菌感染的小鼠模型可以用于评估脂质体成分在降低细菌数量上的作用。小鼠肺部及肾脏中妥布霉素的活性可以通过微生物测定实验来进行评估。
实验结果表明，LipoBiEDT-TOB可以有效破坏细菌的群体感应信号分子，而且可以明显降低脂肪酶、壳多糖酶以及蛋白水解酶的产生。而且对小鼠进行三次处理后，细菌计数CFU的结果明显降低了。
最后研究者表示，这种新型脂质体可以有效降低绿脓杆菌群体感应系统信号分子以及毒力因子的产生，可以明显肺部纤维化囊肿病人慢性感染的治疗效果。这就为开发治疗细菌感染的新型疗法提供了帮助。（生物谷Bioon.com）
doi:10.1128/AAC.01634-12
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Efficacy of Liposomal Bismuth-Ethanedithiol Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection
Moayad Alhariri and Abdelwahab Omri#
We sought to investigate alterations in quorum-sensing signal molecule N-acyl homoserine lactone secretion and in the release of Pseudomonas aeruginosa virulence factors as well as in vivo antimicrobial activity of Bismuth-Ethanedithiol Incorporated in a Liposome-Loaded Tobramycin Formulation (LipoBiEDT-TOB) administered to rats chronically infected with P. aeruginosa. Quorum-sensing signal molecule N-acyl homoserine lactone was monitored by a biosensor organism. P. aeruginosa virulence factors were assessed spectrophotometrically. Agar beads model of chronic Pseudomonas lung infection in rats were used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorum-sensing signal molecules N-3-oxo-dodeccanoylhomoserine lactone and N-butanoylhomoserine lactone as well as significantly (P<0.05) reduced lipase, chitinase and protease productions. Twenty four hours after 3 treatments, the CFU counts in lungs treated with LipoBiEDT-TOB were of 3 log10CFU/lungs comparatively to 7.4 and 4.7 log10/lungs respectively in untreated and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 μg/lungs while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 μg/kidneys, but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.
