title: Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model.
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.
authors.affiliation: Department of Biomedical Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff CF5 2YB, UK. Electronic address: mbeeton@cardiffmet.ac.uk.
authors.forename: M L
authors.initials: ML
authors.lastname: Beeton
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Alves
authors.affiliation: School of Healthcare Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Enright
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: A T A
authors.initials: AT
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006458:Hemolymph / Q000382:microbiology; D006801:Humans; D007915:Lepidoptera / Q000382:microbiology / Q000502:physiology; D011552:Pseudomonas Infections / Q000382:microbiology / Q000517:prevention & control* / Q000628:therapy*; D017105:Pseudomonas Phages / Q000254:growth & development*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000821:virology*; D016019:Survival Analysis
keywords: Galleria mellonella; Infection model; Phage therapy; Pseudomonas aeruginosa