Bacteriophage and their Potential to Regulate Bacterial Populations

Primary Researchers:

Bacteriophage as Natural Microbiome Engineers

Bacterial viruses are highly abundant in the enteric microbiome. As agents of lysis and gene transfer they are “natural engineers” of microbial communities. As such, they offer tools for the development of therapeutic applications, such as phage therapy; and understanding their dynamics provides insight into the mechanistic basis of development and progression of diseases such as inflammatory bowel disease. Our overall aims are to build a database of diverse human microbiome associated bacterial viruses, the Microbiome Phage database (MPdb), and to explicitly test the feasibility of assembling specific virus cocktails for microbiome engineering. The rationale for our approach is that:

Large culture collections of well-characterized bacteria-virus pairs associated with the human microbiome are not available. By generating such a collection, and characterizing member virus host ranges, we provide a general resource for the engineering and deployment of virus cocktails targeting defined bacterial strains or groups within microbial communities.
The interpretation of metagenomic sequencing libraries of microbiome viromes is currently limited by the abundance of unassignable viral “dark matter”. By expressly targeting recovery of diverse groups of viruses we aim to significantly increase the fraction of viral metagenome sequences that can be annotated as bona fide viruses and thus be evaluated for associations with disease.

This project has four specific aims:

Establish rapid bacteriophage isolation protocols from human microbiome samples.
Evaluate the diversity and specificity of bacteriophages for harmful bacteria.
Determine whether outgrowth of harmful bacteria in the gut is limited by phages already present in the host microbiome prior to their arrival.
Assemble therapeutic bacteriophage cocktails to rapidly suppress growth of harmful bacteria in the gut.