title: Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models.
abstract: Bacteria can be genetically engineered to kill specific pathogens or inhibit their virulence. We previously developed a synthetic genetic system that allows a laboratory strain of Escherichia coli to sense and kill Pseudomonas aeruginosa in vitro. Here, we generate a modified version of the system, including a gene encoding an anti-biofilm enzyme, and use the probiotic strain Escherichia coli Nissle 1917 as host. The engineered probiotic shows in vivo prophylactic and therapeutic activity against P. aeruginosa during gut infection in two animal models (Caenorhabditis elegans and mice). These findings support the further development of engineered microorganisms with potential prophylactic and therapeutic activities against gut infections.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
authors.forename: In Young
authors.initials: IY
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Elvin
authors.initials: E
authors.lastname: Koh
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Adison
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: March
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.affiliation: NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.|Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore S 119074, Singapore.
authors.forename: Yung Seng
authors.identifier: 0000-0002-1253-0557
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.|NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics*; D005260:Female; D005759:Gastroenteritis / Q000382:microbiology / Q000628:therapy*; D005818:Genetic Engineering / Q000379:methods; D051379:Mice; D008813:Mice, Inbred ICR; D000074041:Microorganisms, Genetically-Modified; D019936:Probiotics / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000382:microbiology / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D014774:Virulence