據(jù)美國物理學家組織網(wǎng)8月18日報道,新加坡的研究人員日前培育出一種經(jīng)過基因修改的大腸桿菌,,這種基因工程菌能夠識別并通過“自爆”的方式殺滅對人體有害的綠膿桿菌。相關(guān)論文8月16日在線發(fā)表在《分子系統(tǒng)生物學》(Molecular Systems Biology )雜志上,。
綠膿桿菌是一種常見細菌,,一般寄生在消化道或呼吸系統(tǒng),具有較強的耐藥性,,近年來已成為醫(yī)院內(nèi)感染的主要細菌,,有研究稱10%的院內(nèi)感染都與其相關(guān),如果被感染者抵抗力較弱甚至會產(chǎn)生致命后果,。傳統(tǒng)療法一般是使用大量的抗生素,,但沒有殺滅致病菌卻殃及有益細菌的事情經(jīng)常發(fā)生。
為了解決這一問題,,新加坡南洋理工大學的科學家闕路寶(Chueh Loo Poh)和馬修·沃克·張(Matthew Wook Chang)對大腸桿菌的DNA(脫氧核糖核酸)進行了修改,使其能夠探測到綠膿桿菌與同類進行交流時所釋放出的一種獨特分子信號LasR,。這種分子信號的出現(xiàn)意味著有大量綠膿桿菌的聚集,。此時,經(jīng)過修改的大腸桿菌就如同一顆“生物感應(yīng)炸彈”一樣會發(fā)生自爆并釋放出大量的綠膿菌素,。這種物質(zhì)對綠膿桿菌具有毒性,,因而起到將其殺滅的作用。實驗顯示,,當這兩種細菌處于單獨的環(huán)境中時,,經(jīng)過人工修改的大腸桿菌能殺滅99%的綠膿桿菌。
研究人員稱,,該研究的一個重要意義是,,為解決新型抗菌藥物匱乏的局面帶來了曙光。由于抗生素的濫用,,細菌的耐藥性不斷增強,,原先的抗菌藥物已經(jīng)越來越無法起到殺滅作用。但新藥研發(fā)周期較長,,對抗菌藥物而言,,在過去10年中真正投放到市場上的只有兩種。這種青黃不接的局面讓不少人深感擔憂,。
雖然這種基因工程菌在實驗中表現(xiàn)良好,,但仍然存有缺憾。研究人員稱,目前這種經(jīng)過修改的大腸桿菌還無法主動尋找目標,,在自爆前它們只能守株待兔地坐等致病菌路過,。他們希望能找到其他類似的細菌來替代大腸桿菌,如果能實現(xiàn)對目標的主動追蹤,,這種方法的殺滅率極有可能達到100%,。
下一步,研究人員將進行小鼠實驗以測試這種療法的有效性,,并確定這種療法對哺乳動物是否有副作用,。(生物谷 Bioon.com)
doi:10.1038/msb.2011.55
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Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen
Nazanin Saeidi, Choon Kit Wong, Tat-Ming Lo, Hung Xuan Nguyen, Hua Ling, Susanna Su Jan Leong, Chueh Loo Poh, Matthew Wook Chang
Synthetic biology aims to systematically design and construct novel biological systems that address energy, environment, and health issues. Herein, we describe the development of a synthetic genetic system, which comprises quorum sensing, killing, and lysing devices, that enables Escherichia coli to sense and kill a pathogenic Pseudomonas aeruginosa strain through the production and release of pyocin. The sensing, killing, and lysing devices were characterized to elucidate their detection, antimicrobial and pyocin release functionalities, which subsequently aided in the construction of the final system and the verification of its designed behavior. We demonstrated that our engineered E. coli sensed and killed planktonic P. aeruginosa, evidenced by 99% reduction in the viable cells. Moreover, we showed that our engineered E. coli inhibited the formation of P. aeruginosa biofilm by close to 90%, leading to much sparser and thinner biofilm matrices. These results suggest that E. coli carrying our synthetic genetic system may provide a novel synthetic biology-driven antimicrobial strategy that could potentially be applied to fighting P. aeruginosa and other infectious pathogens.