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

Susanne Meile, Jiemin Du, Samuel Staubli, Sebastian Grossmann, Hendrik Koliwer-Brandl, Pietro Piffaretti, Lorenz Leitner, Cassandra I. Matter, Jasmin Baggenstos, Laura Hunold, Sonja Milek, Christian Guebeli, Marko Kozomara-Hocke, Vera Neumeier, Angela Botteon, Jochen Klumpp, Jonas Marschall, Shawna McCallin, Reinhard Zbinden, Thomas M. Kessler, Martin J. Loessner, Matthew Dunne () and Samuel Kilcher ()
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39863-x

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