Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2021

Phage adsorption and inactivation by the Eukaryotic cell could have repercussions for the efficacy of phage therapy. (#7)

Marion C Bichet 1 , Jeremy J Barr 1
  1. School of Biological sciences, Monash University, Clayton, Victoria, Australia

For over 100 years, bacteriophages have been thought of as viruses that strictly interact with their bacterial hosts. But it is becoming increasingly apparent that bacteriophages also interact with eukaryotic cells, and in the context of phage therapy, these interactions can have major impacts on the health and immune response of a patient. Yet the cellular mechanisms for phage binding, uptake and transport within eukaryotic cells remain unknown. In the Bichet et al. 2021 research article, we investigate how eukaryotic cells engulf, traffic and process phages and what their cellular responses are. To this end, we used real-time microscopy to visualise the entry of phages within cells and we quantified the number of phages that remain active when in contact with the cells using two quantification methods, plaque assay and ddPCR. We were able to demonstrate rapid phage adsorption to cells within less than thirty seconds, which resulted in the inactivation of 90% of phages adsorbed. We further show that cells preferentially uptake smaller phages particles (<100 nm) rather than larger ones (>150 nm) and that the rate of uptake is highly dependent on the cell type. In the context of phage therapy, where large doses of phage monocultures are administered to a patient to combat bacterial infection, the stability and persistence of phages within the body are critical. Here, we demonstrate that eukaryotic cells rapidly adsorb and inactivate phages. Thus, the cell layers of the human body represent a potential sink for circulating phages, which could impact innate immune responses and the efficacy of phage therapy.

  1. Bichet et al. 2021, "Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy", iScience; https://doi.org/10.1016/j.isci.2021.102287