Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model
M L Beeton1, D R Alves2, M C Enright3
1Department of Biomedical Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff CF5 2YB, UK.
Abstract:
The Galleria mellonella infection model was used to assess the in vivo efficacy of phage therapy against laboratory and clinical strains of Pseudomonas aeruginosa. In a first series of experiments, Galleria were infected with the laboratory strain P. aeruginosa PAO1 and were treated with varying multiplicity of infection (MOI) of phages either 2h post-infection (treatment) or 2h pre-infection (prevention) via injection into the haemolymph. To address the kinetics of infection, larvae were bled over a period of 24h for quantification of bacteria and phages. Survival rates at 24h when infected with 10 cells/larvae were greater in the prevention versus treatment model (47% vs. 40%, MOI=10; 47% vs. 20%, MOI=1; and 33% vs. 7%, MOI=0.1). This pattern held true when 100 cells/larvae were used (87% vs. 20%, MOI=10; 53% vs. 13%, MOI=1; 67% vs. 7%, MOI=0.1). By 24h post-infection, phages kept bacterial cell numbers in the haemolymph 1000-fold lower than in the non-treated group. In a second series of experiments using clinical strains to further validate the prevention model, phages protected Galleria when infected with both a bacteraemia (0% vs. 85%) and a cystic fibrosis (80% vs. 100%) isolate. Therefore, this study validates the use of G. mellonella as a simple, robust and cost-effective model for initial in vivo examination of P. aeruginosa-targeted phage therapy, which may be applied to other pathogens with similarly low infective doses.
Insights
Phage therapy effectively prevents and treats Pseudomonas aeruginosa infections in Galleria mellonella larvae. This insect model shows promise for evaluating phage efficacy against bacterial pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing significant healthcare-associated infections.
- Phage therapy offers a potential alternative to antibiotics for combating bacterial infections.
- The Galleria mellonella infection model is a valuable tool for in vivo antimicrobial efficacy studies.
Purpose of the Study:
- To evaluate the in vivo efficacy of phage therapy against Pseudomonas aeruginosa.
- To assess the effectiveness of phage therapy in both prevention and treatment settings.
- To validate the Galleria mellonella model for preclinical phage therapy research.
Main Methods:
- Larvae of Galleria mellonella were infected with Pseudomonas aeruginosa laboratory and clinical strains.
- Phage therapy was administered either pre-infection (prevention) or post-infection (treatment).
- Bacterial and phage loads were quantified over 24 hours, and survival rates were assessed.
Main Results:
- Phage therapy significantly improved survival rates in both prevention and treatment models.
- Prevention strategies demonstrated higher efficacy compared to treatment strategies.
- Phages reduced bacterial loads by 1000-fold in vivo.
- Phages protected Galleria larvae against clinical isolates of P. aeruginosa.
Conclusions:
- Galleria mellonella is a robust and cost-effective model for evaluating P. aeruginosa phage therapy.
- Phage therapy shows significant potential for controlling P. aeruginosa infections.
- This model can be extended to study phage efficacy against other pathogens.
