細(xì)菌的生物被膜相比單一的細(xì)菌對于多種抗生素更具有抗性,,近日,來自丹麥哥本哈根大學(xué)的研究者指出一種大蒜的成分可以有效地阻止細(xì)菌產(chǎn)生生物被膜,,這就為我們治療囊性纖維化病人帶來了希望,。研究者的相關(guān)研究論文刊登在了近日的國際雜志Antimicrobial Agents and Chemotherapy上。
早期研究中,,研究者Givskov和其同事指出,,在小鼠實驗中,大蒜的粗提物可以抑制綠膿桿菌群體感應(yīng)系統(tǒng)所控制的基因的表達(dá),,而且可以幫助小鼠快速清除綠膿桿菌,。研究者的發(fā)現(xiàn)使得研究者有信心去分離并且鑒定出大蒜中純的活性成分。
研究者發(fā)現(xiàn)大蒜中的這種活性成分是艾喬恩(Ajoene),,Ajoene可以明顯抑制綠膿桿菌控制的11個基因的表達(dá),,這些受群體感應(yīng)系統(tǒng)控制的基因?qū)τ诰G膿桿菌引發(fā)感染至關(guān)重要。研究者同時發(fā)現(xiàn)Ajoene可以降低綠膿桿菌鼠李糖脂(保護(hù)細(xì)菌不受白細(xì)胞的傷害)的產(chǎn)生,,在妥布霉素中加入Ajoene可以殺滅將近90%的細(xì)菌,。
研究者的研究是用天然的化合物以細(xì)菌群體感性系統(tǒng)為靶點來治療細(xì)菌的感染,研究者Jakobsen表示,,在囊性纖維化病人機(jī)體中,,綠膿桿菌的感染可以直接導(dǎo)致支氣管擴(kuò)張,肺部纖維化以及呼吸衰竭甚至死亡。盡管我們當(dāng)前集中進(jìn)行抗生素聯(lián)合治療,,可是囊性纖維化病人的存活時間也只有大約40年,,而且這些病人機(jī)體伴隨著復(fù)雜的細(xì)菌感染。目前研究者
Jakobsen的團(tuán)隊致力于研究Ajoene抵抗細(xì)菌生物被膜的研究,,研究者希望找到一條基于Ajoene的治療路徑,。
最后Jakobsen表示,大蒜藥用已經(jīng)數(shù)千年了,,大蒜不僅具有潛在的抗菌能力,,而且可以抗病毒、抗真菌,、抗原生動物,;而且對于強(qiáng)化心血管和免疫系統(tǒng)亦有益處。
(生物谷:T.Shen編譯)
doi:10.1128/AAC.05919-11
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Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing
Tim Holm Jakobsena, Maria van Gennipa, Richard Kerry Phippsb, Meenakshi Sundaram Shanmughamc, Louise Dahl Christensena, Morten Alhedea, Mette Eline Skindersoed, Thomas Bovbjerg Rasmussene, Karlheinz Friedrichf, Friedrich Uthef, Peter Østrup Jenseng, Claus Moserg, Kristian Fog Nielsenb, Leo Eberlh, Thomas Ostenfeld Larsenb, David Tannerc, Niels Høibya,g, Thomas Bjarnsholta,g and Michael Givskova,i
In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.