Microbes residing in the vertebrate intestinal tract contribute significantly to host health and disease. The mechanisms by which intestinal bacteria interact with each other and their host are poorly understood because most of these microbes are not amenable to genetic manipulation. We propose to combine phenotypic selection after chemical mutagenesis, and population-based whole genome sequencing to identify genes functionally associated with mucin degradation in the Akkermansia muciniphila, a genetically intractable mucin-degrading gut microbe that has been associated with protection from high-fat induced metabolic disorders and inflammation. The proposed work will seek to identify molecular mechanisms of gut colonization and optimal pro-biotic functions.
The availability of defined microbial mutants is essential to unambiguously determine if the functions ascribed to a gut microbe are responsible for its impact on host metabolic health. Indeed, a major gap in microbiome studies is the ability to link a microbial biochemical activity to a host phenotype. This proposal will develop novel methods and experimental platforms to provide direct tests of gene-enzyme relationships for new microbial activities and provide systems for in vivo testing the genetic basis for gut microbe interactions with its host and other microbes.
