2012年9月2日 訊 /生物谷BIOON/ --近日,，來自加拿大蒙特利爾大學(xué)的研究者發(fā)現(xiàn)了一種可以使細(xì)菌“繳械投降”的方法,，這種新型方法不是直接通過藥物殺滅細(xì)菌，而是實(shí)現(xiàn)細(xì)菌自動(dòng)繳械,，然后機(jī)體通過自身免疫系統(tǒng)來摧毀細(xì)菌,。研究者Christian解釋道，為了更好地理解這種新型策略,，你可以將有害細(xì)菌想象為黑武士達(dá)斯-維德,，而抗毒力藥物就可以拿去其身上的盔甲和光劍，使其繳械,，然后被消滅,。
在細(xì)菌中，毒力因子常常扮演著重要的致病角色,，由致病菌引發(fā)的感染性疾病是人類的一大主要災(zāi)難,，幸運(yùn)的是在20世紀(jì)中期抗生素的發(fā)明，使大部分的致病細(xì)菌感染得到了有效地控制。
研究者的研究成果刊登在了國際雜志Chemistry & Biology上,，文章中，研究團(tuán)隊(duì)發(fā)現(xiàn)了一種可以靶位細(xì)菌生物系統(tǒng)（IV型分泌系統(tǒng)）蛋白質(zhì)的一種小分子物質(zhì),，IV型分泌系統(tǒng)對(duì)于細(xì)菌發(fā)揮毒力必不可少,。研究者Baron說道，我們可以以該致病分泌系統(tǒng)的蛋白VirB8為靶點(diǎn)進(jìn)行攻擊,，從而來消除細(xì)菌的毒力,，進(jìn)而殺滅細(xì)菌。
這種新型療法對(duì)于許多耐藥細(xì)菌的治療都非常重要,，當(dāng)然研究者還表示,，這種抗毒力的藥物還需要在臨床試驗(yàn)中進(jìn)一步證明其效用和價(jià)值。（生物谷Bioon.com）
編譯自：A new way to disarm bacterial infections
doi:10.1016/j.chembiol.2012.07.007
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PMID:
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
