Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization

Kennedy, Megan S.; Zhang, Manjing; DeLeon, Orlando; Bissell, Jacie; Trigodet, Florian; Lolans, Karen; Temelkova, Sara; Carroll, Katherine T.; Fiebig, Aretha; Deutschbauer, Adam; Sidebottom, Ashley M.; Lake, Joash; Henry, Chris; Rice, Phoebe A.; Bergelson, Joy; Chang, Eugene B.

doi:10.6082/fth5w-th295

Published August 21, 2023 | Version v1

Journal article Open

Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization

1. University of Chicago
2. Michigan State University
3. Lawrence Berkeley National Laboratory
4. Argonne National Laboratory

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.

Data availability

All sequencing data, including DNA and RNA datasets, have been deposited at NCBI Sequence Read Archive and are publicly available as of the date of publication. Accession numbers are listed in the key resources table.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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