In our studies we mainly use the fish pathogen Flavobacterium columnare and its viruses, phages, as a model system. We also work with other phage-bacterium systems originating from the aquatic environment to understand the diversity and evolutionary origins of bacterial viruses.
1. Phage-bacterium arms race
Our recent study publisher in Nature Communications shows the molecular details of a long-term (2003-2014) phage–bacterium arms race in the environment. Bacteria (Flavobacterium columnare) were generally resistant to phages from the past and susceptible to phages isolated in years after bacterial isolation. Bacterial resistance selected for increased phage infectivity and host range, which was also associated with expansion of phage genome size. We identified two CRISPR loci in the bacterial host: a type II-C locus and a type VI-B locus. While maintaining a core set of conserved spacers, phage-matching spacers appeared in the variable ends of both loci over time. The spacers mostly target the terminal end of the phage genomes, which also exhibit the most variation across time, resulting in arms race-like changes in the protospacers of the coevolving phage population.
2. Phage-host interactions and phage therapy
Our recent study demonstrates that phage can efficiently be used to control F. columnare infections. The phage FCL-2 can reduce the transmission of columnaris disease in a rainbow trout population, delay the onset of disease and persist in the flow-through system for up to 48 hours. These results are encouraging for development of phage therapy.
Phages infecting F. columnare can be isolated fish farms. The host range of F. columnare phages is narrow and they do not infect other bacterial species. When co-cultured in the presence of phage, bacteria lose their virulence and motility. The loss of these fundamental features by gaining phage resistance provides an interesting starting point for future studies in trade-offs between virulence and phage resistance.
Our research on phage therapy is funded by a grant from Jane and Aatos Erkko Foundation, Key project funding by Academy of Finland, and through the BONUS FLAVOPHAGE project.
3. Evolution of virulence in intensive farming
F. columnare infections in aquaculture have become more frequent and severe over the years, suggesting evolution of virulence. The ecological and epidemiological conditions of fish farming environment may select for more virulent and competitive pathogen strains, in both short and long time scales. Indeed, F. columnare strains isolated from nature have low virulence or are completely non-virulent, whereas fish farming isolates have high virulence and may lead to 100% mortality within the fish population.
F. columnare can exhibit three different colony morphology variants, which differ in their virulence, adherence and gliding motility. When the bacteria isolated from disease outbreaks, free water and biofilms are of the rhizoid morphotype, rough and soft variants appear in laboratory in response to starvation, change of nutrient concentration and when co-cultured with phage.
As only the rhizoid type of F. columnare is virulent in fish, the analysis of the other variants can help in characterization of virulence factors in this bacterium. Indeed, it seems that coordinated structure of the colony and membrane vesicles are connected with virulence. Nutrients influence the expression of the virulence factor chondroitinase in F. columnare, highlighting the importance of environmental conditions in regulating disease epidemics.
Our core research themes are:
Gabriel De Freitas Almeida