Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization
Megan S. Kennedy,
Manjing Zhang,
Orlando DeLeon,
Jacie Bissell,
Florian Trigodet,
Karen Lolans,
Sara Temelkova,
Katherine T. Carroll,
Aretha Fiebig,
Adam Deutschbauer,
Ashley M. Sidebottom,
Joash Lake,
Chris Henry,
Phoebe A. Rice,
Joy Bergelson,
Eugene B. Chang
Affiliations
Megan S. Kennedy
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
Manjing Zhang
Committee on Microbiology, The University of Chicago, Chicago, IL, USA
Orlando DeLeon
Department of Medicine, The University of Chicago, Chicago, IL, USA
Jacie Bissell
Department of Medicine, The University of Chicago, Chicago, IL, USA
Florian Trigodet
Department of Medicine, The University of Chicago, Chicago, IL, USA
Karen Lolans
Department of Medicine, The University of Chicago, Chicago, IL, USA
Sara Temelkova
Department of Medicine, The University of Chicago, Chicago, IL, USA
Katherine T. Carroll
Department of Medicine, The University of Chicago, Chicago, IL, USA
Aretha Fiebig
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
Adam Deutschbauer
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, USA
Ashley M. Sidebottom
Duchossois Family Institute, Department of Biomedical Sciences, The University of Chicago, Chicago, IL, USA
Joash Lake
Committee on Immunology, The University of Chicago, Chicago, IL, USA
Chris Henry
Mathematics and Computer Science Division, Argonne National Laboratory, Lemont, IL, USA
Phoebe A. Rice
Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA
Joy Bergelson
Committee on Microbiology, The University of Chicago, Chicago, IL, USA
Eugene B. Chang
Department of Medicine, The University of Chicago, Chicago, IL, USA; Corresponding author
Summary: 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.
