Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

This grant will investigate the production of anti-phage secondary metabolites by Streptomyces bacteria. Phages are viruses that infect and kill bacteria. They are the most abundant biological entity on earth, outnumbering bacteria by a factor of ten. It is estimated that Avogadro’s number of phage infections occurs each second on earth. This pervasive selection pressure combined with the ubiquity of phages in the environment has led to the evolution of a wide array of bacterial anti-phage defense mechanisms. For example, bacteria can inhibit phage attachment at the cell surface, block genome replication, or degrade the phage genome using restriction enzymes or the CRISPR-Cas system. Given the intensity of the bacteria-phage arms race, it is highly probable that other defense mechanisms remain to be delineated. Characterization of these mechanisms will provide important insight into how phage-host interactions shape the microbial world.

Previous studies searching for compounds that inhibit E. coli phage replication identified a number of secondary metabolites produced by different species of Streptomyces that actively block phage propagation. The high frequency with which we identified these secondary metabolites among Streptomyces strains led us to hypothesize that secondary metabolites provide a previously uncharacterized anti-phage defense system. In this proposal, we will determine if Streptomyces use secondary metabolites as an endogenous anti-phage defense mechanism and will identify genetic pathways through which these molecules are synthesized. We have developed a unique platform for pursuing these studies that combines high-throughput screening with detailed biochemical and genetic studies that will allow us to identify molecules and directly link them with anti-phage activities. This work will ascribe biological functions to previously uncharacterized secondary metabolites and provide new insight into the evolutionary arms race between bacteria and phages, which plays important roles in nutrient cycling, global climate, biodiversity, and species distribution.