Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy

Marion C. Bichet, Wai Hoe Chin, William Richards, Yu Wei Lin, Laura Avellaneda-Franco, Catherine A. Hernandez, Arianna Oddo, Oleksandr Chernyavskiy, Volker Hilsenstein, Adrian Neild, Jian Li, Nicolas Hans Voelcker, Ruzeen Patwa, Jeremy J. Barr

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Abstract

It is increasingly apparent that bacteriophages, viruses that infect bacteria and more commonly referred to as simply phages, have tropisms outside their bacterial hosts. Using live tissue culture cell imaging, we demonstrate that cell type, phage size, and morphology play a major role in phage internalization. Uptake was validated under physiological conditions using a microfluidic device. Phages adhered to mammalian tissues, with adherent phages being subsequently internalized by macropinocytosis, with functional phages accumulating intracellularly. We incorporated these results into a pharmacokinetic model demonstrating the potential impact of phage accumulation by cell layers, which represents a potential sink for circulating phages in the body. During phage therapy, high doses of phages are directly administered to a patient in order to treat a bacterial infection, thereby facilitating broad interactions between phages and mammalian cells. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.

Original languageEnglish
Article number102287
Number of pages32
JournaliScience
Volume24
Issue number4
DOIs
Publication statusPublished - 23 Apr 2021

Keywords

  • Immunology
  • Microbiology
  • Virology

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