近日，國(guó)際著名雜志PLoS Pathogens在線刊登了英國(guó)研究人員的最新研究成果“Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System,，”,，文章中，作者揭示了致病菌感染人體和農(nóng)作物的新機(jī)制,，為后期開發(fā)新型抗生素治療感染性疾病提供了一定的參考,。
近年來,，隨著致病細(xì)菌對(duì)抗生素耐藥性的升高,，不管是在人類中還是在農(nóng)業(yè)上，都亟待需要一些創(chuàng)新型的方法來應(yīng)對(duì)細(xì)菌的感染,；英國(guó)皇后瑪麗學(xué)院的研究者最近研究了細(xì)菌的二型分泌系統(tǒng)（Type II secretion system）,，該系統(tǒng)是大腸桿菌和霍亂弧菌等致病菌的毒性因子分泌系統(tǒng)，細(xì)菌可以利用該系統(tǒng)將毒素輸送至感染者體內(nèi),，從而給病人帶來嚴(yán)重的難以治愈的疾病,。
領(lǐng)導(dǎo)此項(xiàng)研究的是Richard Pickersgill教授，他表示：“細(xì)菌的分泌系統(tǒng)可以運(yùn)送毒性因子到病人的組織中,，如果我們知道這些分泌系統(tǒng)是如何工作的,，我們就可以想辦法阻斷這種運(yùn)輸途徑，破壞細(xì)菌的分泌系統(tǒng),，從而減少細(xì)菌的感染,。”
為了進(jìn)行成功的感染,，革蘭氏陰性菌必須通過細(xì)胞內(nèi)膜和外膜將毒性因子注入到宿主的組織中，Richard Pickersgill教授指出,，細(xì)菌的毒性因子是通過外膜膜孔來運(yùn)輸?shù)?，這些膜孔是由很多蛋白亞單位構(gòu)成的，這些蛋白亞單位也是通過一種蛋白質(zhì)進(jìn)行引導(dǎo)從而定位的,。引導(dǎo)蛋白與諸多蛋白亞單位相互作用,，最終形成外膜的膜孔，如果引導(dǎo)蛋白缺失了,，在細(xì)菌中,，只會(huì)形成內(nèi)膜膜孔，不會(huì)形成外膜膜孔,，這樣就會(huì)導(dǎo)致細(xì)菌的分泌系統(tǒng)失去作用,，崩潰掉。Richard Pickersgill教授還補(bǔ)充說：“如果我們可以成功的干擾引導(dǎo)蛋白使它失去作用,，這樣,，細(xì)菌就不能建立完善的分泌體系，就會(huì)大大阻止疾病的發(fā)生了,。”
大腸桿菌和霍亂弧菌同樣可以利用二型分泌系統(tǒng)來感染食物,，造成食物腐敗，比如Dickeya dadantii,；近年來,，由于全球氣候變化引起的濕熱天氣，尤其是在英國(guó),，因?yàn)闈駸崽鞖饩壒?，?xì)菌感染農(nóng)作物造成的農(nóng)作物腐敗的現(xiàn)象越來越多。
Richard Pickersgill教授領(lǐng)導(dǎo)的研究組希望他們的研究結(jié)果能夠給制藥公司提供一些理論基礎(chǔ),，供醫(yī)藥公司來開發(fā)新的抗生素,，同樣給農(nóng)業(yè)科學(xué)家也能夠提供一定的建議，采取新的措施來阻止細(xì)菌感染農(nóng)作物,。（生物谷: T.Shen編譯）
doi:10.1371/journal.ppat.1002531
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Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System
Shuang Gu1#, Saima Rehman1#, Xiaohui Wang2, Vladimir E. Shevchik2*, Richard W. Pickersgill1*
Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this process is poorly understood and its structural basis is unknown. Here we report the crystal structure of the pilotin of the T2SS that comprises an arrangement of four α-helices profoundly different from previously solved pilotins from the T3SS and T4P and known four α-helix bundles. The architecture can be described as the insertion of one α-helical hairpin into a second open α-helical hairpin with bent final helix. NMR, CD and fluorescence spectroscopy show that the pilotin binds tightly to 18 residues close to the C-terminus of the secretin. These residues, unstructured before binding to the pilotin, become helical on binding. Data collected from crystals of the complex suggests how the secretin peptide binds to the pilotin and further experiments confirm the importance of these C-terminal residues in vivo.
