1. Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine.
- Author
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Meile S, Du J, Staubli S, Grossmann S, Koliwer-Brandl H, Piffaretti P, Leitner L, Matter CI, Baggenstos J, Hunold L, Milek S, Guebeli C, Kozomara-Hocke M, Neumeier V, Botteon A, Klumpp J, Marschall J, McCallin S, Zbinden R, Kessler TM, Loessner MJ, Dunne M, and Kilcher S
- Subjects
- Humans, Escherichia coli genetics, Klebsiella genetics, Enterococcus genetics, Anti-Bacterial Agents pharmacology, Bacteriophages genetics, Urinary Tract Infections microbiology
- 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 ≥10
3 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., (© 2023. The Author(s).)- Published
- 2023
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