Intracellular Pseudomonas aeruginosa persist and evade antibiotic treatment in a wound infection model.

Persistent bacterial infections evade host immunity and resist antibiotic treatments through various mechanisms that are difficult to evaluate in a living host. Pseudomonas aeruginosa is a main cause of chronic infections in patients with cystic fibrosis (CF) and wounds. Here, by immersing wounded z...

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Main Authors: Stéphane Pont, Flore Nilly, Laurence Berry, Anne Bonhoure, Morgan A Alford, Mélissande Louis, Pauline Nogaret, Manjeet Bains, Olivier Lesouhaitier, Robert E W Hancock, Patrick Plésiat, Anne-Béatrice Blanc-Potard
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-02-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012922
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Summary:Persistent bacterial infections evade host immunity and resist antibiotic treatments through various mechanisms that are difficult to evaluate in a living host. Pseudomonas aeruginosa is a main cause of chronic infections in patients with cystic fibrosis (CF) and wounds. Here, by immersing wounded zebrafish embryos in a suspension of P. aeruginosa isolates from CF patients, we established a model of persistent infection that mimics a murine chronic skin infection model. Live and electron microscopy revealed persisting aggregated P. aeruginosa inside zebrafish cells, including macrophages, at unprecedented resolution. Persistent P. aeruginosa exhibited adaptive resistance to several antibiotics, host cell permeable drugs being the most efficient. Moreover, persistent bacteria could be partly re-sensitized to antibiotics upon addition of anti-biofilm molecules that dispersed the bacterial aggregates in vivo. Collectively, this study demonstrates that an intracellular location protects persistent P. aeruginosa in vivo in wounded zebrafish embryos from host innate immunity and antibiotics, and provides new insights into efficient treatments against chronic infections.
ISSN:1553-7366
1553-7374