Journal
ACS SYNTHETIC BIOLOGY
Volume 3, Issue 4, Pages 228-237Publisher
AMER CHEMICAL SOC
DOI: 10.1021/sb400077j
Keywords
synthetic biology; quorum sensing; Pseudomonas aeruginosa; directed motility; biofilrn; antimicrobial peptide
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Funding
- National Medial Research Council of Singapore [CBRG11nov109]
- U.S. Defense Threat Reduction Agency [HDTRA1-13-0037]
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Recent examples of new genetic circuits that enable cells to acquire biosynthetic capabilities, such as specific pathogen killing, present an attractive therapeutic application of synthetic biology. Herein, we demonstrate a novel genetic circuit that reprograms Escherichia coli to specifically recognize, migrate toward, and eradicate both dispersed and biofilm-encased pathogenic Pseudomonas aeruginosa cells. The reprogrammed E. coli degraded the mature biofilm matrix and killed the latent cells encapsulated within by expressing and secreting the antimicrobial peptide microcin S and the nuclease DNasel upon the detection of quorum sensing molecules naturally secreted by P. aeruginosa. Furthermore, the reprogrammed E. coli exhibited directed motility toward the pathogen through regulated expression of CheZ in response to the quorum sensing molecules. By integrating the pathogen-directed motility with the dual antimicrobial activity in E. coli, we achieved signifincantly improved killing activity against planktonic and mature biofilm cells due to target localization, thus creating an active pathogen seeking killer E. coli.
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