Construction, characterization and efficacy assessment of Recombinant Phage Endolysins as enzybiotic against Aeromonas salmonicida, the causative agent of furunculosis (ASAPHLYR)

The application of bacteriophages in the field of aquaculture is the topic of a large number of publications nowadays. Bacteriophages are well adapted to this environment, since they are usually found in aquatic environments. The control of the bacterial infections are often based on antimicrobial (tetracyclines, quinolones, sulfonamides,…). However, the diffusion of antimicrobials by water contributes to the pollution of the environment and to the emergence and diffusion of antimicrobial resistances. Bacteriophages represent a credible alternative but the medical world has to pay attention to the emergence of resistance against phages to avoid repeating the antibiotic resistance story. Endolysins which are phage's enzymes able to degrade the peptidoglycan can be also used as theray (enzybiotic) with a reduced risk of resistance emergence. This project will focus on Aeromonas (A.) salmonicida, a primary fish pathogen that causes furunculosis in salmonids, carp and perch, as well as septicaemia in a variety of fish. The aims of this project will be to develop enzybiotic based on engineered endolysins targeting A. salmonicida, to compare the emergence of resistances and to assess their efficacy in a preliminary in vivo model. To reach these objectives we propose to isolate and characterize bacteriophages targeting this Gram-negative bacteria. Then, natural phage-encoded endolysins will be identified and genetically engineered to target and kill A. salmonicida. A characterization of the bacterial resistance emergence induced by phages versus engineered endolysins use will be performed and their efficacies will be assessed in vivo in a Galleria mellonella larvae model.