Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization. 2023

Megan S Kennedy, and Manjing Zhang, and Orlando DeLeon, and Jacie Bissell, and Florian Trigodet, and Karen Lolans, and Sara Temelkova, and Katherine T Carroll, and Aretha Fiebig, and Adam Deutschbauer, and Ashley M Sidebottom, and Joash Lake, and Chris Henry, and Phoebe A Rice, and Joy Bergelson, and Eugene B Chang
Medical Scientist Training Program, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA; Department of Ecology & Evolution, The University of Chicago, Chicago, IL, USA.

To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free mice to determine whether and how the genetic requirements for colonization shift over time. Combining a high-throughput functional genetics assay and transcriptomics, we find that gene usage changes drastically during the first days of colonization, shifting from high expression of amino acid biosynthesis genes to broad upregulation of diverse polysaccharide utilization loci. Within the first week, metabolism becomes centered around utilization of a predominant dietary oligosaccharide, and these changes are largely sustained through 6 weeks of colonization. Spontaneous mutations in wild-type Bt also evolve around this locus. These findings highlight the importance of considering temporal colonization dynamics in developing more effective microbiome-based therapies.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000064 Acclimatization Adaptation to a new environment or to a change in the old. Acclimation
D000070077 Bacteroides thetaiotaomicron A species of Bacteroides that is a major constituent of the human GUT MICROBIOTA. It normally produces enzymes important for the digestion of vegetable matter. However, it can also cause OPPORTUNISTIC INFECTIONS that result in intra-abdominal SEPSIS; BACTEREMIA; and PERITONITIS.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020869 Gene Expression Profiling The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell. Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays
D064307 Microbiota The full collection of microbes (bacteria, fungi, virus, etc.) that naturally exist within a particular biological niche such as an organism, soil, a body of water, etc. Human Microbiome,Microbiome,Microbiome, Human,Microbial Community,Microbial Community Composition,Microbial Community Structure,Community Composition, Microbial,Community Structure, Microbial,Community, Microbial,Composition, Microbial Community,Human Microbiomes,Microbial Communities,Microbial Community Compositions,Microbial Community Structures,Microbiomes,Microbiotas

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