Nanna Rørbo:
Bacteriophage interactions with Vibrio anguillarum and the potential for phage therapy in marine aquacult

Date: 23-12-2017    Supervisor: Mathias Middelboe

The aquaculture industry is expanding due to an increasing demand for food with the world’s population growing. However, aquaculture often experience disease outbreaks generally caused by opportunistic pathogens, including Vibrio anguillarum. This bacterium is the causative agent of the disease vibriosis which affects a lot of different fish species. As in the rest of the world, an increase in antibiotic resistant bacteria is also observed in the aquaculture industry making chemotherapeutics futile. Bacteriophage therapy offers a great potential in treatment and control of Vibrio anguillarum in aquaculture, however, more knowledge is needed regarding the phagehost interaction in order to accomplish success. The current PhD thesis address the phage-host interactions in Vibrio anguillarum and the potential of phage therapy in treating vibriosis outbreaks in eggs and larvae of cod and turbot.

Lysogeny is widespread in the Vibrio community which underscore the lysogenic phages influence on bacterial evolution and functional properties. Highly genetically similar Vibrio phages, termed H20-like prophages, were isolated across large geographical scales being present both as freeliving phages and as prophages in V. anguillarum genomes. The H20-like phages’ widespread presence suggests a mutualistic interaction which selects for co-existence with V. anguillarum. In aquaculture, especially the larvae and fry are vulnerable to pathogens, and they are not susceptible to alternatives to antibiotics, e.g. vaccines. The lytic broad-host-range phage KVP40 was applied to cod and turbot larvae to control different V. anguillarum strains. We observed that phage KVP40 was able to reduce and/or delay the mortality. Further, phage KVP40 was also able to reduced the mortality imposed by the natural bacterial background present in the larvae, emphasizing its potential as a therapeutic agent.

In phage therapy the resistance mechanisms after phage exposure and the impact on the host are not fully understood. A molecular and mechanistic understanding of resistance mechanisms and virulence properties of the host is essential for developing properly phage therapy. In this PhD thesis phage-resistant V. anguillarum strains were whole-genome sequenced to explain different resistance mechanisms, and their virulence properties were tested on cod larvae. The strains consisted of both non-mutational and mutational resistance mechanisms, probably depending on phage exposure and environmental conditions, which affected the pathogenicity.