Bioengineering bacteriophages to enhance the sensitivity of phage amplification-based paper fluidic detection of bacteria

Biosens Bioelectron. 2016 Aug 15:82:14-9. doi: 10.1016/j.bios.2016.03.047. Epub 2016 Mar 22.

Abstract

Bacteriophage (phage) amplification is an attractive method for the detection of bacteria due to a narrow phage-host specificity, short amplification times, and the phages' ability to differentiate between viable and non-viable bacterial cells. The next step in phage-based bacteria detection is leveraging bioengineered phages to create low-cost, rapid, and easy-to-use detection platforms such as lateral flow assays. Our work establishes the proof-of-concept for the use of bioengineered T7 phage strains to increase the sensitivity of phage amplification-based lateral flow assays. We have demonstrated a greater than 10-fold increase in sensitivity using a phage-based protein reporter, maltose-binding protein, over the detection of replicated T7 phage viron itself, and a greater then 100-fold increase in sensitivity using a phage-based enzymatic reporter, alkaline phosphatase. This increase in sensitivity enabled us to detect 10(3)CFU/mL of Escherichia coli in broth after 7h, and by adding a filter concentration step, the ability to detect a regulatory relevant E. coli concentration of 100CFU/100mL in inoculated river water after 9h, where the current standard requires days for results. The combination of the paper fluidic format with phage-based detection provides a platform for the development of novel diagnostics that are sensitive, rapid, and easy to use.

Keywords: Bacteriophage; Biosensor, water quality; E. coli; Genetic engineering; Lateral flow assay; Synthetic biology.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Bacterial Proteins / genetics
  • Bacteriophage T7 / genetics*
  • Bioengineering / methods*
  • Biosensing Techniques / methods*
  • Environmental Monitoring / methods*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification*
  • Escherichia coli / virology*
  • Genetic Engineering / methods
  • Limit of Detection
  • Maltose-Binding Proteins / genetics
  • Rivers / microbiology*
  • Up-Regulation

Substances

  • Bacterial Proteins
  • Maltose-Binding Proteins
  • Alkaline Phosphatase