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Updated: May 28, 2025
A Delayed Inoculation Model of Chronic Pseudomonas aeruginosa Wound Infection
Published on: February 20, 2020
Intracellular Pseudomonas aeruginosa persist and evade antibiotic treatment in a wound infection model
Stéphane Pont1, Flore Nilly1, Laurence Berry1
1Laboratory of Pathogens and Host Immunity (LPHI), Université de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
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.
Insights
This study reveals that persistent Pseudomonas aeruginosa bacteria hide inside zebrafish cells, evading immunity and antibiotics. Dispersing these bacterial aggregates can restore antibiotic sensitivity, offering new treatment strategies for chronic infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Zebrafish Models
Background:
- Persistent bacterial infections pose significant challenges due to immune evasion and antibiotic resistance.
- Pseudomonas aeruginosa is a key pathogen in chronic conditions like cystic fibrosis and non-healing wounds.
Purpose of the Study:
- To establish a zebrafish embryo model for persistent bacterial infections.
- To investigate the mechanisms of immune evasion and antibiotic resistance by persistent P. aeruginosa.
- To explore novel therapeutic strategies for chronic P. aeruginosa infections.
Main Methods:
- Utilized wounded zebrafish embryos immersed in P. aeruginosa isolates from cystic fibrosis patients.
- Employed live and electron microscopy to visualize bacterial localization and aggregation within host cells.
- Assessed bacterial antibiotic resistance and the efficacy of anti-biofilm molecules in vivo.
Main Results:
- Successfully modeled persistent P. aeruginosa infection in zebrafish embryos, mimicking chronic skin infections.
- Observed P. aeruginosa residing intracellularly within macrophages, protected from host immunity.
- Demonstrated adaptive antibiotic resistance, with cell-permeable drugs showing higher efficiency.
- Showed partial re-sensitization to antibiotics upon dispersion of bacterial aggregates with anti-biofilm agents.
Conclusions:
- Intracellular localization protects persistent P. aeruginosa from host defenses and antibiotic treatment in vivo.
- Dispersing bacterial aggregates is a promising strategy to enhance antibiotic efficacy against chronic infections.
- The zebrafish embryo model offers high-resolution insights into persistent bacterial pathogenesis and treatment.
