title: Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen.
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.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Saeidi
authors.forename: Choon Kit
authors.initials: CK
authors.lastname: Wong
authors.forename: Tat-Ming
authors.initials: TM
authors.lastname: Lo
authors.forename: Hung Xuan
authors.initials: HX
authors.lastname: Nguyen
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Susanna Su Jan
authors.initials: SS
authors.lastname: Leong
authors.forename: Chueh Loo
authors.initials: CL
authors.lastname: Poh
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000494:pharmacology; D000898:Antibiosis / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015374:Biosensing Techniques / Q000379:methods; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000096:biosynthesis; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D030781:Organisms, Genetically Modified / Q000235:genetics*; D010957:Plasmids; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D011709:Pyocins / Q000096:biosynthesis / Q000494:pharmacology; D053038:Quorum Sensing / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D058615:Synthetic Biology / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C109860:N-(3-oxododecanoyl)homoserine lactone; D011709:Pyocins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D006714:Homoserine; D015107:4-Butyrolactone