Abstract
Phage-based approaches have gained increasing interest as sustainable alternative strategies to antibiotic treatment or as prophylactic measures against disease outbreaks in aquaculture. The potential of three methods (oral, bath, and injection) for delivering a two-component phage mixture to rainbow trout fry for controlling Flavobacterium psychrophilum infections and reduce fish mortality was investigated using bacteriophages FpV4 and FPSV-D22. For the oral administration experiment, bacteriophages were applied on feed pellets by spraying (1.6 × 108 PFU g–1) or by irreversible immobilization (8.3 × 107 PFU g–1), using the corona discharge technology (Fixed Phage Ltd.). The fish showed normal growth for every group and no mortality was observed prior to infection as well as in control groups during the infection. Constant detection of phages in the intestine (∼103 PFU mg–1) and more sporadic occurrence in kidney, spleen, and brain was observed. When fish were exposed to F. psychrophilum, no significant effect on fish survival, nor a direct impact on the number of phages in the sampled organs, were detected. Similarly, no significant increase in fish survival was detected when phages were delivered by bath (1st and 2nd bath: ∼106 PFU ml–1; 3rd bath: ∼105 PFU ml–1). However, when phages FpV4 and FPSV-D22 (1.7 × 108 PFU fish–1) were administered by intraperitoneal injection 3 days after the bacterial challenge, the final percent survival observed in the group injected with bacteriophages FpV4 and FPSV-D22 (80.0%) was significantly higher than in the control group (56.7%). The work demonstrates the delivery of phages to fish organs by oral administration, but also suggests that higher phage dosages than the tested ones may be needed on feed pellets to offer fish an adequate protection against F. psychrophilum infections.
Highlights
Phage therapy relies on the bactericidal activity of lytic bacteriophages, which infect and kill specific bacterial hosts by lysing infected cells and releasing phage progeny to the environment [Twort, 1915; Roux, 2011; reviewed in Salmond and Fineran (2015); Dion et al (2020)]
In order to evaluate the potential protection conferred by the phage cocktail targeting F. psychrophilum, rainbow trout fry (1.5–2 g) were fed either with phage-immobilized (8.3 × 107 ± 2.5 × PFU g−1) or phage-sprayed (1.6 × ± 4.8 × 107 PFU g−1) feed at 2% of their body weight for 12 days before bacterial challenge (Table 1, Figure 1A and Supplementary Figures 1A,B)
Efficiency of Phage Delivery: Percentage of Isolation of F. psychrophilum and Its Phages in Fish Organs The qualitative detection of bacteriophages in intestine, kidney, spleen, and brain of fish fed with phage immobilized feed, phage sprayed feed, and control feed verified the presence of bacteriophages in treated fish and thereby the delivery of phages through the feed pellets before any manipulation (IP injection with either F. psychrophilum or sterile TYES-B) (Figure 2)
Summary
Phage therapy relies on the bactericidal activity of lytic bacteriophages ( called phages), which infect and kill specific bacterial hosts by lysing infected cells and releasing phage progeny to the environment [Twort, 1915; Roux, 2011; reviewed in Salmond and Fineran (2015); Dion et al (2020)]. Despite the many benefits of phage therapy, various challenges have been faced such as the development of phage resistant bacteria, the inefficient delivery of phages in high dosages at the infection site, and the phage clearance activity from the organism mediated by the immune cells [reviewed in Culot et al (2019); Kowalska et al (2020)]. Castillo et al (2012) studied the application of phages in rainbow trout and Atlantic salmon delivering bacteriophages (109 PFU fish−1) by intraperitoneal (IP) injection simultaneously to F. psychrophilum (108 CFU fish−1). In order to assess the potential of phage-based control of F. psychrophilum infections in rainbow trout, combined studies on phage delivery efficiency and fish mortality in challenge experiments are required
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
