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

Autor: 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, Samuel Kilcher
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-39863-x
Popis: 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.
Databáze: Directory of Open Access Journals