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

Despite the remarkable microbial diversity found within humans, our ability to link genes to phenotypes is based upon a handful of model microorganisms. We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants. We also present a tool for the quantification of strains from metagenomic sequencing data, enabling the identification of genes that predict bacterial fitness. Competitive growth is reproducible under laboratory conditions and attributable to intrinsic growth rates and resource utilization. Unique signatures of in vivo competition in gnotobiotic mice include an adhesin enriched in poor colonizers. Together, these computational and experimental resources represent a strong foundation for the continued mechanistic dissection of the Coriobacteriia and a template that can be applied to study other genetically intractable taxa. [Display omitted] •Curated analysis of paired genome and isolate collection for the study of Coriobacteriia•Eggerthella lenta is genotypically and phenotypically diverse•Development of tools for discovering and validating effector genes in E. lenta•Intra-species competition in E. lenta is correlated with a putative host adhesin Bisanz et al. focus on an in-depth study of Eggerthella lenta and the Coriobacteriia class: highly prevalent members of the human gut microbiota which have been poorly described. Through construction of a paired isolate and genome library, they validate tools for comparative genomic approaches to uncover effectors of xenobiotic metabolism and fitness.