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Updated: Sep 16, 2025
Modeling Persistent Pseudomonas aeruginosa Infection in Wounded Zebrafish Larvae
Published on: June 13, 2025
Modeling Pseudomonas aeruginosa-Staphylococcus aureus interactions in zebrafish to assess the host inflammatory
Floriane Costes1, Flore Nilly1, Aurélia Rousset2
1Laboratory of Pathogens and Host Immunity (LPHI), CNRS, Inserm, Université de Montpellier, Montpellier, 34095, France.
Abstract:
Investigating the interplay between polymicrobial colonization and host response in the context of chronic infections is a complex issue. The interaction between Staphylococcus aureus and Pseudomonas aeruginosa, which frequently co-infect patients with chronic diseases like cystic fibrosis (CF), can be either competitive or coexistent. How these interaction states can influence the host response remains an open question for which relevant infection models are needed. In this study, we investigated co-infections by P. aeruginosa and S. aureus in zebrafish (Danio rerio), a non-mammalian model well established for the study of the host innate immune response. Using a wound infection method and a trio of strains co-isolated from a CF patient, we provide an in vivo co-infection model that recapitulates the competitive and coexistent bacterial interactions observed in vitro. The inflammatory response, monitored through the expression of specific cytokines at the infection site or in the whole larvae, was stronger with P. aeruginosa than S. aureus in the context of mono-infection. Upon co-infection, a competitive or coexistent interaction between P. aeruginosa and S. aureus appeared to slightly modulate this response. Moreover, the RT-qPCR profile of cytokine response observed in zebrafish larvae was similar to the one observed after infection of human lung epithelial cells. Thus, the zebrafish embryo appears as a relevant model to study persistent co-infection with P. aeruginosa and S. aureus, offering unique opportunities to address the host response in this polymicrobial context.
Insights
Zebrafish models chronic co-infections by Staphylococcus aureus and Pseudomonas aeruginosa. This study shows zebrafish can model polymicrobial interactions and host immune responses seen in human cystic fibrosis patients.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Polymicrobial infections, particularly Staphylococcus aureus and Pseudomonas aeruginosa co-infections, are common in chronic diseases like cystic fibrosis (CF).
- Understanding how bacterial interactions (competitive vs. coexistent) influence host response in these chronic infections is crucial.
- Relevant in vivo models are needed to study these complex polymicrobial dynamics and host immune interactions.
Purpose of the Study:
- To establish and validate a zebrafish (Danio rerio) co-infection model for studying Staphylococcus aureus and Pseudomonas aeruginosa interactions.
- To investigate how bacterial interaction states (competitive or coexistent) affect the host innate immune response in vivo.
- To compare the host response in zebrafish larvae with that observed in human lung epithelial cells.
Main Methods:
- Developed a wound infection method in zebrafish larvae to model co-infections with P. aeruginosa and S. aureus.
- Utilized a trio of bacterial strains co-isolated from a cystic fibrosis patient to mimic clinical scenarios.
- Monitored inflammatory response by measuring cytokine expression at the infection site and in whole larvae using RT-qPCR.
Main Results:
- The zebrafish co-infection model successfully recapitulated in vitro observed competitive and coexistent bacterial interactions.
- Monoinfections elicited a stronger inflammatory response with P. aeruginosa compared to S. aureus.
- Co-infection modulated the inflammatory response, with bacterial interaction states showing a slight impact on cytokine profiles, mirroring human lung cell responses.
Conclusions:
- Zebrafish embryos provide a relevant and powerful in vivo model for studying persistent polymicrobial co-infections involving P. aeruginosa and S. aureus.
- This model offers unique opportunities to investigate the host innate immune response dynamics in complex co-infection scenarios.
- Findings suggest zebrafish models can effectively bridge the gap between in vitro observations and human disease pathology in chronic infections.
