Design of a Broad-Range Bacteriophage Cocktail That Reduces Pseudomonas aeruginosa Biofilms and Treats Acute Infections in Two Animal Models

Francesca Forti (1) , Dwayne Roach (2) , Marco Cafora (1) , Maria Pasini (1) , David Horner (1) , Ersilia Fiscarelli (3) , Martina Rossitto (3) , Lisa Cariani (4) , Federica Briani (1) , Laurent Debarbieux (2) , Daniela Ghisotti (1)

1 Department of Biosciences [Milano]
2 Département de Microbiologie - Department of Microbiology
3 IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital
4 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

The alarming diffusion of multidrug-resistant (MDR) bacterial strains requires investigations on nonantibiotic therapies. Among such therapies, the use of bacteriophages (phages) as antimicrobial agents, namely, phage therapy, is a promising treatment strategy supported by the findings of recent successful compassionate treatments in Europe and the United States. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains of Pseudomonas aeruginosa, including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance. We demonstrated that the cocktail composed of four novel phages (PYO2, DEV, E215 and E217) and two previously characterized phages (PAK_P1 and PAK_P4) was able to lyse P. aeruginosa both in planktonic liquid cultures and in biofilms. In addition, we showed that the phage cocktail could cure acute respiratory infection in mice and treat bacteremia in wax moth (Galleria mellonella) larvae. Furthermore, administration of the cocktail to larvae prior to bacterial infection provided prophylaxis. In this regard, the efficiency of the phage cocktail was found to be unaffected by the MDR or mucoid phenotype of the pseudomonal strain. The cocktail was found to be superior to the individual phages in destroying biofilms and providing a faster treatment in mice. We also found the Galleria larva model to be cost-effective for testing the susceptibility of clinical strains to phages, suggesting that it could be implemented in the frame of developing personalized phage therapies.

Mots clés: Galleria mellonella; Pseudomonas aeruginosa; bacteriophages; cystic fibrosis; phage therapy

Domaines: Bactériologie

Francesca Forti, Dwayne Roach, Marco Cafora, Maria Pasini, David Horner, et al.. Design of a Broad-Range Bacteriophage Cocktail That Reduces Pseudomonas aeruginosa Biofilms and Treats Acute Infections in Two Animal Models. Antimicrobial Agents and Chemotherapy, 2018, 62 (6), ⟨10.1128/AAC.02573-17⟩. ⟨pasteur-01827311⟩