生物谷報(bào)道:美國(guó)科學(xué)家利用生物合成方法改造病毒,然后用改造后的病毒成功清除了含有有害細(xì)菌的生物薄膜,。這一方法可望用于食品和醫(yī)療等行業(yè)的器械消毒,。
細(xì)菌生物薄膜是生長(zhǎng)于生物器官或物體表面的細(xì)菌群落。許多人類(lèi)疾病與細(xì)菌生物薄膜有關(guān),,食品加工設(shè)備或醫(yī)療器械內(nèi)部的細(xì)菌生物薄膜會(huì)成為長(zhǎng)期傳染源,。細(xì)菌生物薄膜的表層膜由多種蛋白質(zhì)、多糖和核酸構(gòu)成,,能大幅減弱抗生素對(duì)細(xì)菌的襲擊,。要有效對(duì)抗細(xì)菌生物薄膜,必須能同時(shí)殺死細(xì)菌并毀壞表層保護(hù)膜,。
美國(guó)麻省理工學(xué)院和波士頓大學(xué)的科學(xué)家在試驗(yàn)中,,使用侵襲細(xì)菌的病毒——噬菌體來(lái)清除生物細(xì)菌薄膜。他們對(duì)襲擊大腸桿菌的T7噬菌體進(jìn)行基因改造,,使其分泌一種能毀壞表層保護(hù)膜的酶,。
研究人員在塑料物品表面培育大腸桿菌生物薄膜,用改造后的T7噬菌體處理,。結(jié)果顯示,,噬菌體能殺死生物薄膜中99.997%的細(xì)菌,殺菌能力比未經(jīng)基因改造的噬菌體高出百倍,。有關(guān)論文發(fā)表在新一期美國(guó)《國(guó)家科學(xué)院學(xué)報(bào)》上,。
根據(jù)美國(guó)對(duì)噬菌體應(yīng)用的規(guī)定,,這一成果尚不能直接用于人類(lèi)藥物。它可望用于食品和醫(yī)療行業(yè)的器械消毒,,也可用于預(yù)防和治療家畜疾病,。(援引新華網(wǎng))
原始出處:
Published online before print June 25, 2007, 10.1073/pnas.0704624104
PNAS | July 3, 2007 | vol. 104 | no. 27 | 11197-11202
Dispersing biofilms with engineered enzymatic bacteriophage
Timothy K. Lu*,, and James J. Collins,
*Harvard–MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Room E25–519, Cambridge, MA 02139; and Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215
Communicated by Hans Kornberg, Boston University, Boston, MA, May 17, 2007 (received for review April 20, 2007)
Synthetic biology involves the engineering of biological organisms by using modular and generalizable designs with the ultimate goal of developing useful solutions to real-world problems. One such problem involves bacterial biofilms, which are crucial in the pathogenesis of many clinically important infections and are difficult to eradicate because they exhibit resistance to antimicrobial treatments and removal by host immune systems. To address this issue, we engineered bacteriophage to express a biofilm-degrading enzyme during infection to simultaneously attack the bacterial cells in the biofilm and the biofilm matrix, which is composed of extracellular polymeric substances. We show that the efficacy of biofilm removal by this two-pronged enzymatic bacteriophage strategy is significantly greater than that of nonenzymatic bacteriophage treatment. Our engineered enzymatic phage substantially reduced bacterial biofilm cell counts by 4.5 orders of magnitude (99.997% removal), which was about two orders of magnitude better than that of nonenzymatic phage. This work demonstrates the feasibility and benefits of using engineered enzymatic bacteriophage to reduce bacterial biofilms and the applicability of synthetic biology to an important medical and industrial problem.
phage therapy | synthetic biology
Fig. 1. Two-pronged attack strategy for biofilm removal with enzymatically active DspB-expressing T7DspB phage. Initial infection of E. coli biofilm results in rapid multiplication of phage and expression of DspB. Both phage and DspB are released upon lysis, leading to subsequent infection as well as degradation of the crucial biofilm EPS component, -1,6-N-acetyl-D-glucosamine (22).
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