A Genomic Toolkit for the Mechanistic Dissection of Intractable Human Gut Bacteria

Area of Science:

• Microbiology
• Genomics
• Human Microbiome Research

Background:

• Human microbiome harbors vast microbial diversity, yet few model organisms exist for gene-phenotype linkage.
• Coriobacteriia, a neglected bacterial taxon, holds broad relevance to human health and disease.

Purpose of the Study:

• To establish a comparative genomics platform for Eggerthella lenta and other Coriobacteriia.
• To develop tools for mapping bacterial phenotypes to genes and sequence variants.
• To identify genes associated with bacterial fitness and competitive advantage.

Main Methods:

• Comparative genomics analysis of Eggerthella lenta and related taxa.
• Development and validation of a phenotype-to-gene mapping tool.
• Creation of a strain quantification tool for metagenomic data.
• In vitro competitive growth experiments.
• In vivo competition studies in gnotobiotic mice.

Main Results:

• Uncovered extensive genetic and metabolic diversity within Coriobacteriia.
• Validated a tool for linking bacterial genes to observed phenotypes and sequence variants.
• Identified genes predicting bacterial fitness using strain quantification from metagenomic data.
• Demonstrated reproducible competitive growth in vitro based on intrinsic rates and resource use.
• Discovered an adhesin enriched in poor colonizers during in vivo competition.

Conclusions:

• The developed platform provides a robust foundation for mechanistic studies of Coriobacteriia.
• The tools enable deeper understanding of genotype-phenotype relationships in genetically intractable bacteria.
• This work serves as a template for studying other under-characterized microbial taxa relevant to human health.