2012年12月2日 訊 /生物谷BIOON/ --近日,，刊登在國(guó)際雜志Antimicrobial Agents and Chemotherapy上刊登的一篇研究報(bào)告“Efficacy of Liposomal Bismuth-Ethanedithiol Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection”中,，來(lái)自勞倫森大學(xué)的研究者揭示了裝有妥布霉素的鉍-乙二硫醇脂質(zhì)體治療綠膿桿菌感染的小鼠的療效。
在本項(xiàng)研究中,，研究者Abdelwahab Omri說(shuō)，我們目的是想要研究當(dāng)鉍-乙二硫醇混合物加入到裝載有妥布霉素的脂質(zhì)體（LipoBiEDT-TOB）中,，其對(duì)于綠膿桿菌群體感應(yīng)信號(hào)分子N-?；呓z氨酸內(nèi)酯以及毒力因子釋放的影響和作用。
其中N-?；呓z氨酸內(nèi)酯信號(hào)分子可以由生物傳感器來(lái)進(jìn)行監(jiān)測(cè),，細(xì)菌毒力因子的釋放可以由分光光度計(jì)進(jìn)行測(cè)量評(píng)估。受細(xì)菌感染的小鼠模型可以用于評(píng)估脂質(zhì)體成分在降低細(xì)菌數(shù)量上的作用,。小鼠肺部及腎臟中妥布霉素的活性可以通過(guò)微生物測(cè)定實(shí)驗(yàn)來(lái)進(jìn)行評(píng)估,。
實(shí)驗(yàn)結(jié)果表明，LipoBiEDT-TOB可以有效破壞細(xì)菌的群體感應(yīng)信號(hào)分子,，而且可以明顯降低脂肪酶,、殼多糖酶以及蛋白水解酶的產(chǎn)生。而且對(duì)小鼠進(jìn)行三次處理后,，細(xì)菌計(jì)數(shù)CFU的結(jié)果明顯降低了,。
最后研究者表示，這種新型脂質(zhì)體可以有效降低綠膿桿菌群體感應(yīng)系統(tǒng)信號(hào)分子以及毒力因子的產(chǎn)生,，可以明顯肺部纖維化囊腫病人慢性感染的治療效果,。這就為開(kāi)發(fā)治療細(xì)菌感染的新型療法提供了幫助,。（生物谷Bioon.com）
doi:10.1128/AAC.01634-12
PMC:
PMID:
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.
