TY - JOUR
T1 - Phage-Mediated Control of Flavobacterium psychrophilum in Aquaculture
T2 - In vivo Experiments to Compare Delivery Methods
AU - Donati, Valentina Laura
AU - Dalsgaard, Inger
AU - Sundell, Krister
AU - Castillo, Daniel
AU - Er-Rafik, Mériem
AU - Clark, Jason
AU - Wiklund, Tom
AU - Middelboe, Mathias
AU - Madsen, Lone
N1 - Funding Information:
The authors would like to thank K?ri Karbech Mouritsen for his excellent technical support during fish experimental trials and fish samplings as well as the fish caretakers of the Blue Unit at the Technical University of Denmark. Funding. This work resulted from the BONUS FLAVOPHAGE project supported by BONUS (Art 185), funded jointly by the EU, Innovation Fund Denmark and Academy of Finland.
Funding Information:
This work resulted from the BONUS FLAVOPHAGE project supported by BONUS (Art 185), funded jointly by the EU, Innovation Fund Denmark and Academy of Finland.
Publisher Copyright:
© Copyright © 2021 Donati, Dalsgaard, Sundell, Castillo, Er-Rafik, Clark, Wiklund, Middelboe and Madsen.
PY - 2021/3/8
Y1 - 2021/3/8
N2 - 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.
AB - 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.
KW - bacteriophages
KW - Flavobacterium psychrophilum
KW - phage-therapy
KW - rainbow trout fry (Oncorhynchus mykiss)
KW - rainbow trout fry syndrome (RTFS)
UR - http://www.scopus.com/inward/record.url?scp=85102936305&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2021.628309
DO - 10.3389/fmicb.2021.628309
M3 - Article
AN - SCOPUS:85102936305
SN - 1664-302X
VL - 12
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 628309
ER -