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

Area of Science:

• Microbiology
• Virology
• Pharmacology

Background:

• Bacteriophages (phages) are viruses that infect bacteria.
• Phages are increasingly recognized for interactions beyond their bacterial hosts.
• Phage therapy involves administering high doses of phages to treat bacterial infections.

Purpose of the Study:

• To investigate the interaction of bacteriophages with mammalian cells.
• To determine the mechanisms and factors influencing phage internalization into non-bacterial cells.
• To assess the implications of these interactions on phage pharmacokinetics and therapy.

Main Methods:

• Live tissue culture cell imaging was employed to observe phage-cell interactions.
• Microfluidic devices were used to validate phage uptake under physiological conditions.
• A pharmacokinetic model was developed incorporating experimental findings.

Main Results:

• Cell type, phage size, and morphology significantly influence phage internalization.
• Phages adhere to mammalian tissues and are internalized via macropinocytosis.
• Functional phages accumulate intracellularly, potentially acting as a "sink" for circulating phages.

Conclusions:

• Phage interactions with mammalian cells, particularly internalization, are significant.
• Intracellular phage accumulation affects phage pharmacokinetics.
• Understanding these interactions is vital for enhancing phage therapy efficacy and safety.