The story of phage therapy against Flavobacterium columnare bacterium : phage-bacterium interactions and utilization of phage therapy in practice
Antibiotic resistance is one of the gravest threats to global health and food production. Resistant strains can cause bacterial infections that were previously treated easily with antibiotics to become lethal. Therefore, there is a need for alternatives to antibiotics, such as bacteriophages, or phages, which are viruses of bacteria. In this thesis, I studied the use of these natural enemies of bacteria against Flavobacterium columnare. F. columnare is a globally emerging bacterium that causes high mortality among fish and large economic losses at freshwater fish farms during warm-water periods unless treated with antibiotics. At fish farms, the spread of antibiotic-resistant strains and antibiotics in the environment is a risk. Phage therapy has the potential to reduce the use of antibiotics against F. columnare. A large collection of new phages that may be used against the pathogen were collected. The most promising phages from this collection were selected so as to study their resistance effects on bacterial strains and to test the different administration routes by which phage therapy can decrease the mortality that columnaris disease causes in rainbow trout. It was seen that F. columnare strain adherence and biofilm formation are lower and, consequently, virulence is weaker as a trade-off for phage resistance. It emerged that the optimal means of controlling F. columnare infections is to bathe fish in phage solution after the first columnaris symptoms appear. Phage bathing before bacterium infection and the use of immobilised phages on plastic sheets slow the progression of bacterial infections. This thesis reinforces the notion that phage therapy holds considerable promise for combatting bacterial infections, but more studies are needed to understand the interactions between different bacterial strains and these phages.
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Jyväskylän yliopistoISBN
978-951-39-9252-1ISSN Search the Publication Forum
2489-9003Contains publications
- Artikkeli I: Runtuvuori‐Salmela, A., Kunttu, H. M. T., Laanto, E., Almeida, G. M. F., Mäkelä, K., Middelboe, M., & Sundberg, L‐R. (2022). Prevalence of genetically similar Flavobacterium columnare phages across aquaculture environments reveals a strong potential for pathogen control. Environmental Microbiology, 24(5), Article 2404-2420. DOI: 10.1111/1462-2920.15901
- Artikkeli II: Runtuvuori-Salmela, A., Sorsa, J., Kunttu, H.M.T., Middelboe, M. & Sundberg, L.-R. Effects of single phage and two phage mixture additions on Flavobacterium columnare growth: Implications of phage resistance. Manuscript.
- Artikkeli III: Kunttu, H. M. T., Runtuvuori-Salmela, A., Sundell, K., Wiklund, T., Middelboe, M., Landor, L., Ashrafi, R., Hoikkala, V., & Sundberg, L.-R. (2021). Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and Type IX Secretion System. Applied and Environmental Microbiology, 87(16), e00812-21. DOI: 10.1128/AEM.00812-21
- Artikkeli IV: Donati, V. L., Dalsgaard, I., Runtuvuori-Salmela, A., Kunttu, H., Jørgensen, J., Castillo, D., Sundberg, L.-R., Middelboe, M., & Madsen, L. (2021). Interactions between Rainbow Trout Eyed Eggs and Flavobacterium spp. Using a Bath Challenge Model : Preliminary Evaluation of Bacteriophages as Pathogen Control Agents. Microorganisms, 9(5), Article 971. DOI: 10.3390/microorganisms9050971
- Artikkeli V: Kunttu, H. M. T., Runtuvuori-Salmela, A., Middelboe, M., Clark, J., & Sundberg, L.-R. (2021). Comparison of Delivery Methods in Phage Therapy against Flavobacterium columnare Infections in Rainbow Trout. Antibiotics, 10(8), Article 914. DOI: 10.3390/antibiotics10080914
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