2012年9月2日 讯 /生物谷BIOON/ --近日，来自加拿大蒙特利尔大学的研究者发现了一种可以使细菌“缴械投降”的方法，这种新型方法不是直接通过药物杀灭细菌，而是实现细菌自动缴械，然后机体通过自身免疫系统来摧毁细菌。研究者Christian解释道，为了更好地理解这种新型策略，你可以将有害细菌想象为黑武士达斯-维德，而抗毒力药物就可以拿去其身上的盔甲和光剑，使其缴械，然后被消灭。
在细菌中，毒力因子常常扮演着重要的致病角色，由致病菌引发的感染性疾病是人类的一大主要灾难，幸运的是在20世纪中期抗生素的发明，使大部分的致病细菌感染得到了有效地控制。
研究者的研究成果刊登在了国际杂志Chemistry & Biology上，文章中，研究团队发现了一种可以靶位细菌生物系统（IV型分泌系统）蛋白质的一种小分子物质，IV型分泌系统对于细菌发挥毒力必不可少。研究者Baron说道，我们可以以该致病分泌系统的蛋白VirB8为靶点进行攻击，从而来消除细菌的毒力，进而杀灭细菌。
这种新型疗法对于许多耐药细菌的治疗都非常重要，当然研究者还表示，这种抗毒力的药物还需要在临床试验中进一步证明其效用和价值。（生物谷Bioon.com）
编译自：A new way to disarm bacterial infections
doi:10.1016/j.chembiol.2012.07.007
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Identification of the Binding Site of Brucella VirB8 Interaction Inhibitors
Mark A. Smith1, Mathieu Coinçon1, Athanasios Paschos3, Benoit Jolicoeur2, Pierre Lavallée2, Jurgen Sygusch1, Christian Baron1, ,
Secretion systems translocate virulence factors of many bacterial pathogens, enabling their survival inside the host organism. Consequently, inhibition strongly attenuates pathogenicity and can be considered a target for novel antimicrobial drugs. The type IV secretion system (T4SS) of the intracellular pathogen Brucella is a prerequisite for its virulence, and in this work we targeted the interactions of the essential assembly factor protein, VirB8, using small-molecule inhibitors. High-throughput screening identified several potent and specific inhibitors, and the target-binding site of these inhibitors was identified by X-ray crystallography, in silico docking, and analysis of the derivates of the inhibitor B8I-2. VirB8 interaction inhibitors bind to a surface groove opposite to the dimerization interface, and by varying the binding-site residues, we were able to determine which residues are required for inhibitor activity. E115 and K182 were found to be especially important, and changes at R114, Y229, and L151 also reduced inhibitor efficiency.
