生物谷报道:美国科学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细菌的生物薄膜。这一方法可望用于食品和医疗等行业的器械消毒。
细菌生物薄膜是生长于生物器官或物体表面的细菌群落。许多人类疾病与细菌生物薄膜有关,食品加工设备或医疗器械内部的细菌生物薄膜会成为长期传染源。细菌生物薄膜的表层膜由多种蛋白质、多糖和核酸构成,能大幅减弱抗生素对细菌的袭击。要有效对抗细菌生物薄膜,必须能同时杀死细菌并毁坏表层保护膜。
美国麻省理工学院和波士顿大学的科学家在试验中,使用侵袭细菌的病毒——噬菌体来清除生物细菌薄膜。他们对袭击大肠杆菌的T7噬菌体进行基因改造,使其分泌一种能毁坏表层保护膜的酶。
研究人员在塑料物品表面培育大肠杆菌生物薄膜,用改造后的T7噬菌体处理。结果显示,噬菌体能杀死生物薄膜中99.997%的细菌,杀菌能力比未经基因改造的噬菌体高出百倍。有关论文发表在新一期美国《国家科学院学报》上。
根据美国对噬菌体应用的规定,这一成果尚不能直接用于人类药物。它可望用于食品和医疗行业的器械消毒,也可用于预防和治疗家畜疾病。(援引新华网)
原始出处:
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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