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Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine

Author

Listed:
  • Susanne Meile

    (Institute of Food Nutrition and Health)

  • Jiemin Du

    (Institute of Food Nutrition and Health)

  • Samuel Staubli

    (Institute of Food Nutrition and Health)

  • Sebastian Grossmann

    (Institute of Food Nutrition and Health)

  • Hendrik Koliwer-Brandl

    (University of Zurich)

  • Pietro Piffaretti

    (Institute of Food Nutrition and Health)

  • Lorenz Leitner

    (Balgrist University Hospital, University of Zurich)

  • Cassandra I. Matter

    (Institute of Food Nutrition and Health)

  • Jasmin Baggenstos

    (Institute of Food Nutrition and Health)

  • Laura Hunold

    (Institute of Food Nutrition and Health)

  • Sonja Milek

    (Balgrist University Hospital, University of Zurich)

  • Christian Guebeli

    (Institute of Food Nutrition and Health)

  • Marko Kozomara-Hocke

    (University Hospital Zurich)

  • Vera Neumeier

    (Balgrist University Hospital, University of Zurich)

  • Angela Botteon

    (Institute of Food Nutrition and Health)

  • Jochen Klumpp

    (Institute of Food Nutrition and Health)

  • Jonas Marschall

    (Washington University School of Medicine)

  • Shawna McCallin

    (Balgrist University Hospital, University of Zurich)

  • Reinhard Zbinden

    (University of Zurich)

  • Thomas M. Kessler

    (Balgrist University Hospital, University of Zurich)

  • Martin J. Loessner

    (Institute of Food Nutrition and Health)

  • Matthew Dunne

    (Institute of Food Nutrition and Health)

  • Samuel Kilcher

    (Institute of Food Nutrition and Health)

Abstract

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥103 CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application.

Suggested Citation

  • Susanne Meile & Jiemin Du & Samuel Staubli & Sebastian Grossmann & Hendrik Koliwer-Brandl & Pietro Piffaretti & Lorenz Leitner & Cassandra I. Matter & Jasmin Baggenstos & Laura Hunold & Sonja Milek & , 2023. "Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39863-x
    DOI: 10.1038/s41467-023-39863-x
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    as
    1. Jiemin Du & Susanne Meile & Jasmin Baggenstos & Tobias Jäggi & Pietro Piffaretti & Laura Hunold & Cassandra I. Matter & Lorenz Leitner & Thomas M. Kessler & Martin J. Loessner & Samuel Kilcher & Matth, 2023. "Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
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    Cited by:

    1. Bogna J. Smug & Krzysztof Szczepaniak & Eduardo P. C. Rocha & Stanislaw Dunin-Horkawicz & Rafał J. Mostowy, 2023. "Ongoing shuffling of protein fragments diversifies core viral functions linked to interactions with bacterial hosts," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jiemin Du & Susanne Meile & Jasmin Baggenstos & Tobias Jäggi & Pietro Piffaretti & Laura Hunold & Cassandra I. Matter & Lorenz Leitner & Thomas M. Kessler & Martin J. Loessner & Samuel Kilcher & Matth, 2023. "Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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