據(jù)美國(guó)物理學(xué)家組織網(wǎng)8月18日?qǐng)?bào)道,，新加坡的研究人員日前培育出一種經(jīng)過(guò)基因修改的大腸桿菌,，這種基因工程菌能夠識(shí)別并通過(guò)“自爆”的方式殺滅對(duì)人體有害的綠膿桿菌。相關(guān)論文8月16日在線(xiàn)發(fā)表在《分子系統(tǒng)生物學(xué)》（Molecular Systems Biology ）雜志上,。
綠膿桿菌是一種常見(jiàn)細(xì)菌,，一般寄生在消化道或呼吸系統(tǒng)，具有較強(qiáng)的耐藥性,，近年來(lái)已成為醫(yī)院內(nèi)感染的主要細(xì)菌,，有研究稱(chēng)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?xí)a(chǎn)生致命后果,。傳統(tǒng)療法一般是使用大量的抗生素,，但沒(méi)有殺滅致病菌卻殃及有益細(xì)菌的事情經(jīng)常發(fā)生。
為了解決這一問(wèn)題,，新加坡南洋理工大學(xué)的科學(xué)家闕路寶（Chueh Loo Poh）和馬修·沃克·張（Matthew Wook Chang）對(duì)大腸桿菌的DNA（脫氧核糖核酸）進(jìn)行了修改,，使其能夠探測(cè)到綠膿桿菌與同類(lèi)進(jìn)行交流時(shí)所釋放出的一種獨(dú)特分子信號(hào)LasR。這種分子信號(hào)的出現(xiàn)意味著有大量綠膿桿菌的聚集,。此時(shí),，經(jīng)過(guò)修改的大腸桿菌就如同一顆“生物感應(yīng)炸彈”一樣會(huì)發(fā)生自爆并釋放出大量的綠膿菌素。這種物質(zhì)對(duì)綠膿桿菌具有毒性,，因而起到將其殺滅的作用,。實(shí)驗(yàn)顯示，當(dāng)這兩種細(xì)菌處于單獨(dú)的環(huán)境中時(shí),，經(jīng)過(guò)人工修改的大腸桿菌能殺滅99%的綠膿桿菌,。
研究人員稱(chēng)，該研究的一個(gè)重要意義是,，為解決新型抗菌藥物匱乏的局面帶來(lái)了曙光,。由于抗生素的濫用，細(xì)菌的耐藥性不斷增強(qiáng),，原先的抗菌藥物已經(jīng)越來(lái)越無(wú)法起到殺滅作用,。但新藥研發(fā)周期較長(zhǎng)，對(duì)抗菌藥物而言,，在過(guò)去10年中真正投放到市場(chǎng)上的只有兩種,。這種青黃不接的局面讓不少人深感擔(dān)憂(yōu)。
雖然這種基因工程菌在實(shí)驗(yàn)中表現(xiàn)良好,，但仍然存有缺憾,。研究人員稱(chēng)，目前這種經(jīng)過(guò)修改的大腸桿菌還無(wú)法主動(dòng)尋找目標(biāo),，在自爆前它們只能守株待兔地坐等致病菌路過(guò),。他們希望能找到其他類(lèi)似的細(xì)菌來(lái)替代大腸桿菌,，如果能實(shí)現(xiàn)對(duì)目標(biāo)的主動(dòng)追蹤，這種方法的殺滅率極有可能達(dá)到100%,。
下一步,，研究人員將進(jìn)行小鼠實(shí)驗(yàn)以測(cè)試這種療法的有效性，并確定這種療法對(duì)哺乳動(dòng)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.
