H2020Individual fellowship2020–2023

CO-DEfENDENCE · Bacteriophages, phage-host interactions and evolution of defence mechanisms in beneficial bacterium Propionibacterium freudenreichii

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-01-01 → 2023-11-09
EU contribution
€219,312
Participants
1
Scheme
MSCA-IF

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Results in brief

Bacteriophages, phage-host interactions and evolution of defence mechanisms in beneficial bacterium Propionibacterium freudenreichii

Propionibacterium freudenreichii is a dairy-associated bacterium with multiple applications in the dairy industry, from adjunct cultures to bioprotective cultures. Many strains of this bacterium have been reported to have probiotic potential and all have the rare capability to produce active vitamin B12. At the same time, the bacterium is relatively poorly studied compared to the other dairy bacteria, especially in the context of their sensitivity to infection with bacterial viruses (bacteriophages). At the beginning of the project, very few bacteriophages infecting this bacterium were characterised, at the same time, the recently published genome sequences of the bacterial strains indicated a broader-than-average arsenal of defence systems protecting the bacteria from bacteriophage infection, despite overall low genetic diversity of the species. This, and the fact that P. freudenreichii is a non-pathogenic representative of the class Actinomycetes, which includes various pathogenic or opportunistic pathogenic bacteria such as Mycobacterium tuberculosis and other mycobacteria or Cutibacterium acnes, means that the results of this project can be translated to these other societally important bacteria as well. The objectives of the project were to isolate and characterise new bacteriophages infecting P. freudenreichii from various samples and to sequence the genomes of the bacteriophages as well as the sensitive and insensitive bacterial hosts in order to better understand the dynamics of bacteriophage-bacterium interactions of the bacteriophage-bacterium pair. As a result, we have characterised two new bacteriophages infecting P. freudenreichii as well as multiple new bacterial strains. We were able to uncover that the scarcity of bacteriophages known for this bacterium are not due to their absence, but due to the efficient defence systems encoded by the bacterium conferring their immunity and complicating phage detection. This also clarified as to why the bacteriophages found to date are comparatively more diverse than the ones known for related bacteria and that one of their strategies for overcoming bacterial defence systems is acquisition of diverse methylases, traditionally associated with Restriction-Modification systems working as protection against bacteriophage infection. One of the bacteriophages will be used in further studies to develop genetic tools for manipulation of Actinomycetes and also for possible phage display application.

Data: CORDIS, © European Union

Project objective

Bacteriophages (phages) infecting Propionibacterium freudenreichii, a bacterium known for production of active vitamin B12 and for causing well-documented benefits to human health, are more diverse than those identified for closely related genera. At the same time, the defence mechanisms protecting the bacterial strains (hosts) from phage attacks are more diverse as well. These two phenomena suggest that P. freudenreichii strains and their phages have experienced complex interactions in phage-bacterium arms race. However, both phages attacking, and the defence mechanisms that this important food-grade Actinobacterium uses to protect itself from phage attacks are currently severely understudied. In CO-DEfENDENCE, I will use an innovative approach of systematic study of the defence mechanisms not only from the perspective of the bacterium, but also from the perspective of the phage. The use of strains and phages isolated from samples of different origin will ensure diversity of material subjected to analyses by a combination of phenotypic, genomic, proteomic and imaging methods. This multidisciplinary approach is possible due to guidance offered by world-class phage specialists at one of the world’s top universities, the University of Copenhagen. The expected result of CO-DEfENDENCE is elucidation of complex interactions between P. freudenreichii and its phages, which led to the high diversity of the phages and the multitude of defence mechanisms employed by the strains. As an added benefit, these results have a great potential for being translated into novel genetic tools and to aid the development of phage therapies, especially those aimed at pathogenic Actinobacteria.

Original text from CORDIS.

Participants

  • KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark

Links

Data: CORDIS, © European Union