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利用工程微生物来感知和消除人类病原体铜绿假单胞菌。

Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen.

机构信息

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.

出版信息

Mol Syst Biol. 2011 Aug 16;7:521. doi: 10.1038/msb.2011.55.

Abstract

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.

摘要

合成生物学旨在系统地设计和构建新的生物系统,以解决能源、环境和健康问题。在此,我们描述了一种合成遗传系统的开发,该系统包括群体感应、杀伤和裂解装置,使大肠杆菌能够通过产生和释放噬菌体来感应和杀死致病性铜绿假单胞菌菌株。我们对感应、杀伤和裂解装置进行了表征,以阐明它们的检测、抗菌和噬菌体释放功能,这随后有助于构建最终系统并验证其设计行为。我们证明,我们工程化的大肠杆菌能够感应并杀死浮游态铜绿假单胞菌,活细胞减少了 99%。此外,我们还表明,我们工程化的大肠杆菌抑制了铜绿假单胞菌生物膜的形成,接近 90%,导致生物膜基质更加稀疏和变薄。这些结果表明,携带我们合成遗传系统的大肠杆菌可能提供一种新的合成生物学驱动的抗菌策略,可能应用于对抗铜绿假单胞菌和其他感染性病原体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fd/3202794/8144fb7fe24a/msb201155-f1.jpg

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