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Pré-Publication, Document De Travail Année : 2024

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

Stephane Pont
  • Fonction : Auteur
Flore Nilly
  • Fonction : Auteur
Laurence Berry
  • Fonction : Auteur
Anne Bonhoure
  • Fonction : Auteur
Morgan Alford
  • Fonction : Auteur
Melissande Louis
  • Fonction : Auteur
Pauline Nogaret
  • Fonction : Auteur
Olivier Lesouhaitier
Robert E.W. Hancock
  • Fonction : Auteur
Patrick Plesiat

Résumé

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 P. aeruginosa in vivo from host innate immunity and antibiotics, and provides new insights into efficient treatments against chronic infections.

Dates et versions

hal-04589686 , version 1 (27-05-2024)

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Stephane Pont, Flore Nilly, Laurence Berry, Anne Bonhoure, Morgan Alford, et al.. Intracellular Pseudomonas aeruginosa persist and evade antibiotic treatment in a wound infection model. 2024. ⟨hal-04589686⟩
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