High throughput platform technology for rapid target identification in personalized phage therapy

Fereshteh Bayat, Arwa Hilal, Mathura Thirugnanasampanthar, Denise Tremblay, Carlos D. M. Filipe, Sylvain Moineau, Tohid F. Didar () and Zeinab Hosseinidoust ()
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Fereshteh Bayat: McMaster University, Hamilton
Arwa Hilal: McMaster University, Hamilton
Mathura Thirugnanasampanthar: McMaster University, Hamilton
Denise Tremblay: Faculté des sciences et de génie, Université Laval
Carlos D. M. Filipe: McMaster University, Hamilton
Sylvain Moineau: Faculté des sciences et de génie, Université Laval
Tohid F. Didar: McMaster University, Hamilton
Zeinab Hosseinidoust: McMaster University, Hamilton

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract As bacteriophages continue to gain regulatory approval for personalized human therapy against antibiotic-resistant infections, there is a need for transformative technologies for rapid target identification through multiple, large, decentralized therapeutic phages biobanks. Here, we design a high throughput phage screening platform comprised of a portable library of individual shelf-stable, ready-to-use phages, in all-inclusive solid tablets. Each tablet encapsulates one phage along with luciferin and luciferase enzyme stabilized in a sugar matrix comprised of pullulan and trehalose capable of directly detecting phage-mediated adenosine triphosphate (ATP) release through ATP bioluminescence reaction upon bacterial cell burst. The tablet composition also enhances desiccation tolerance of all components, which should allow easier and cheaper international transportation of phages and as a result, increased accessibility to therapeutic phages. We demonstrate high throughput screening by identifying target phages for select multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli, and Staphylococcus aureus with targets identified within 30-120 min.

Date: 2024
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DOI: 10.1038/s41467-024-49710-2

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