PUBLICATION

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

Authors
Pont, S., Nilly, F., Berry, L., Bonhoure, A., Alford, M.A., Louis, M., Nogaret, P., Bains, M., Lesouhaitier, O., Hancock, R.E.W., Plésiat, P., Blanc-Potard, A.B.
ID
ZDB-PUB-250214-15
Date
2025
Source
PLoS pathogens   21: e1012922 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Anti-Bacterial Agents*/pharmacology
  • Anti-Bacterial Agents*/therapeutic use
  • Biofilms/drug effects
  • Cystic Fibrosis/drug therapy
  • Cystic Fibrosis/microbiology
  • Disease Models, Animal*
  • Humans
  • Persistent Infection/microbiology
  • Pseudomonas Infections*/drug therapy
  • Pseudomonas Infections*/immunology
  • Pseudomonas Infections*/microbiology
  • Pseudomonas aeruginosa*/drug effects
  • Wound Infection*/drug therapy
  • Wound Infection*/microbiology
  • Zebrafish*/microbiology
PubMed
39946497 Full text @ PLoS Pathog.
Abstract
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.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping