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bioRxiv · 10.1101/2025.07.30.667455

Human cell-derived extracellular vesicles exhibit anti-biofilm effects against Pseudomonas aeruginosa

Solomon, T. J.·Byrne, C. M.·Boledovic, S. S.·Flumen, E. J.·Pirolli, N. H.·Powsner, E. H.·Jay, S. M.
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Abstract

The need for new antimicrobial approaches is one of the most pressing issues in modern medicine. A particular pathogen of concern is multidrug resistant Pseudomonas aeruginosa, which is implicated in over 1 million deaths worldwide yearly. One potential class of novel antimicrobials is extracellular vesicles (EVs), which have been found to have intrinsic antimicrobial and anti-virulence properties. Here, the antimicrobial activity of EVs on P. aeruginosa was explored in the context of biofilms of hyper-virulent strain PA14. We identified the human monocyte cell line THP-1 as a promising source of EVs for this application, inducing reduced PA14 biofilm formation in a dose-dependent manner. THP-1 EVs were not found to affect P. aeruginosa growth planktonically within the biofilm assay or in shaken culture. Additionally, we demonstrate that anti-biofilm effects were conserved with similar efficacy across THP-1 monocyte and differentiated THP-1 macrophage-derived EVs. Further, EVs from induced pluripotent stem cell-derived mesenchymal stem/stromal cells (iMSCs) also reduced PA14 biofilm formation to a similar extent as THP-1 EVs, while EVs from human embryonic kidney cells (HEK293T) had a similar effect to its media control. This work indicates that human cell-derived EVs from several sources possess biological and/or physical properties that reduce PA14 biofilm formation.

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Solomon, T. J., Byrne, C. M., Boledovic, S. S., Flumen, E. J., Pirolli, N. H., Powsner, E. H., Jay, S. M.. 2025-07-30. Human cell-derived extracellular vesicles exhibit anti-biofilm effects against Pseudomonas aeruginosa. https://doi.org/10.1101/2025.07.30.667455

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