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

Cell Host Microbe. 2020 Jun 10;27(6):1001-1013.e9. doi: 10.1016/j.chom.2020.04.006. Epub 2020 Apr 28.

Abstract

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.

Keywords: Coriobacteriia; Eggerthella lenta; colonization; comparative genomics; fitness; human gut microbiome; metabolism; metabolomics.

MeSH terms

  • Actinobacteria / classification
  • Actinobacteria / drug effects
  • Actinobacteria / genetics
  • Actinobacteria / isolation & purification
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / genetics*
  • Bacteria / isolation & purification*
  • Dissection / methods*
  • Gastrointestinal Microbiome / genetics*
  • Gastrointestinal Microbiome / physiology
  • Gastrointestinal Tract / microbiology
  • Genes, Bacterial / genetics
  • Genomics*
  • Germ-Free Life
  • Humans
  • Metagenome
  • Metagenomics
  • Mice
  • Microbial Sensitivity Tests
  • Multigene Family
  • Phenotype
  • Polymorphism, Genetic

Substances

  • Anti-Bacterial Agents

Supplementary concepts

  • Eggerthella lenta