title: Reprogramming microbes to be pathogen-seeking killers.
abstract: 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 DNaseI 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.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459.
authors.forename: In Young
authors.initials: IY
authors.lastname: Hwang
authors.forename: Mui Hua
authors.initials: MH
authors.lastname: Tan
authors.forename: Elvin
authors.initials: E
authors.lastname: Koh
authors.forename: Chun Loong
authors.initials: CL
authors.lastname: Ho
authors.forename: Chueh Loo
authors.initials: CL
authors.lastname: Poh
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018441:Biofilms; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D053038:Quorum Sensing / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; C020411:microcin; D003850:Deoxyribonuclease I