细菌的生物被膜相比单一的细菌对于多种抗生素更具有抗性,近日,来自丹麦哥本哈根大学的研究者指出一种大蒜的成分可以有效地阻止细菌产生生物被膜,这就为我们治疗囊性纤维化病人带来了希望。研究者的相关研究论文刊登在了近日的国际杂志Antimicrobial Agents and Chemotherapy上。
早期研究中,研究者Givskov和其同事指出,在小鼠实验中,大蒜的粗提物可以抑制绿脓杆菌群体感应系统所控制的基因的表达,而且可以帮助小鼠快速清除绿脓杆菌。研究者的发现使得研究者有信心去分离并且鉴定出大蒜中纯的活性成分。
研究者发现大蒜中的这种活性成分是艾乔恩(Ajoene),Ajoene可以明显抑制绿脓杆菌控制的11个基因的表达,这些受群体感应系统控制的基因对于绿脓杆菌引发感染至关重要。研究者同时发现Ajoene可以降低绿脓杆菌鼠李糖脂(保护细菌不受白细胞的伤害)的产生,在妥布霉素中加入Ajoene可以杀灭将近90%的细菌。
研究者的研究是用天然的化合物以细菌群体感性系统为靶点来治疗细菌的感染,研究者Jakobsen表示,在囊性纤维化病人机体中,绿脓杆菌的感染可以直接导致支气管扩张,肺部纤维化以及呼吸衰竭甚至死亡。尽管我们当前集中进行抗生素联合治疗,可是囊性纤维化病人的存活时间也只有大约40年,而且这些病人机体伴随着复杂的细菌感染。目前研究者
Jakobsen的团队致力于研究Ajoene抵抗细菌生物被膜的研究,研究者希望找到一条基于Ajoene的治疗路径。
最后Jakobsen表示,大蒜药用已经数千年了,大蒜不仅具有潜在的抗菌能力,而且可以抗病毒、抗真菌、抗原生动物;而且对于强化心血管和免疫系统亦有益处。
(生物谷:T.Shen编译)
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.