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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / pharmacology
  • Antibiosis / genetics
  • Bacterial Proteins* / biosynthesis
  • Bacterial Proteins* / pharmacology
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Biosensing Techniques / methods
  • Escherichia coli / chemistry
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli / pathogenicity
  • Gene Expression Regulation, Bacterial / drug effects
  • Genes, Reporter
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / biosynthesis
  • Homoserine / analogs & derivatives*
  • Homoserine / pharmacology
  • Humans
  • Organisms, Genetically Modified / genetics*
  • Plasmids
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Pyocins* / biosynthesis
  • Pyocins* / pharmacology
  • Quorum Sensing / drug effects*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • Synthetic Biology / methods*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • N-(3-oxododecanoyl)homoserine lactone
  • Pyocins
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Homoserine
  • 4-Butyrolactone