Tail-engineered phage P2 enables delivery of antimicrobials into multiple gut pathogens

Jidapha Fa-Arun, Yang Wei Huan, Elise Darmon, Baojun Wang

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Bacteriophages can be reprogrammed to deliver antimicrobials for therapeutic and biocontrol purposes and are a promising alternative treatment to antimicrobial-resistant bacteria. Here, we developed a bacteriophage P4 cosmid system for the delivery of a Cas9 antimicrobial into clinically relevant human gut pathogens Shigella flexneri and Escherichia coli O157:H7. Our P4 cosmid design produces a high titer of cosmid-transducing units without contamination by a helper phage. Further, we demonstrate that genetic engineering of the phage tail fiber improves the transduction efficiency of cosmid DNA in S. flexneri M90T as well as allows recognition of a nonnative host, E. coli O157:H7. We show that the transducing units with the chimeric tails enhanced the overall Cas9-mediated killing of both pathogens. This study demonstrates the potential of our P4 cas9 cosmid system as a DNA sequence-specific antimicrobial against clinically relevant gut pathogenic bacteria.
Original languageEnglish
Pages (from-to)596-607
Number of pages12
JournalACS Synthetic Biology
Volume12
Issue number2
Early online date2 Feb 2023
DOIs
Publication statusPublished - 17 Feb 2023

Keywords / Materials (for Non-textual outputs)

  • bacteriophage P2/P4
  • phage-based delivery vector
  • cas9 antimicrobial
  • tail fiber engineering
  • escherichia coli O157:H7
  • shigella flexneri

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