Quantifying rapid bacterial evolution and transmission within the mouse intestine

Vasquez, Kimberly S.; Willis, Lisa; Cira, Nate; Ng, Katharine M.; Pedro, Miguel F.; Aranda-Díaz, Andrés; Rajendram, Manohary; Yu, Feiqiao Brian; Higginbottom, Steven K.; Neff, Norma; Sherlock, Gavin; Xavier, Karina B.; Quake, Stephen R.; Sonnenburg, Justin L.; Good, Benjamin H; Huang, Kerwyn Casey

doi:10.1016/j.chom.2021.08.003

Cited by 31 publications

(44 citation statements)

References 45 publications

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“…Consistent with previous observations in other bacterial species (1)(2)(3)(4), we found that a handful of lineages expanded to intermediate frequencies (>1%) in vivo by day 16 (Fig. 1B-E), indicating rapid positive selection on a subset of the lineages.…”

supporting

confidence: 92%

“…Yet despite their importance, the evolutionary drivers of this in vivo adaptation -and their dependence on the host environment -are only starting to be uncovered.Traditional sequencing approaches have a limited ability to address these questions, since they can only observe the handful of lineages that manage to reach appreciable frequencies within a host. By this time, successful lineages have often acquired multiple distinct mutations (4,6,12). This makes it difficult to resolve their underlying fitness benefits, or the pleiotropic tradeoffs that they encounter in different host conditions (2).…”

mentioning

confidence: 99%

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Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Wong

Good

2022

Preprint

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Gut microbiota can adapt to their host environment by rapidly acquiring new mutations. However, the dynamics of this process are difficult to characterize in dominant gut species in their complex in vivo environment. Here we show that the fine-scale dynamics of genome-wide transposon libraries can enable quantitative inferences of these in vivo evolutionary forces. By analyzing >400,000 lineages across four human Bacteroides strains in gnotobiotic mice, we observed positive selection on thousands of previously hidden mutations – most of which were unrelated to their original gene knockouts. The spectrum of fitness benefits varied between species, and displayed diverse tradeoffs over time and in different dietary conditions. These results suggest that within-host adaptations arise from an intense competition between numerous contending mutations, which can strongly influence their emergent evolutionary tradeoffs.

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confidence: 92%

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confidence: 99%

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Wong

Good

2022

Preprint

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“…5B). Notably, the last gene of PUL24 encodes an α-galactosidase (BT1871), which is predicted to confer the ability to hydrolyze the α-1,6 glycosidic linkage in raffinose family oligosaccharides (RFOs), a major component of the fiber-rich diet that our mice were fed (22). Though this study focuses on understanding the shifting genetic determinants of colonization over time, we recognize that the effect of diet is intrinsic to the results of any gut microbiome study.…”

Section: Resultsmentioning

confidence: 99%

Dynamic genetic adaptation of Bacteroides thetaiotaomicron murine gut colonization

Zhang

Kennedy

DeLeon

et al. 2022

Preprint

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To understand how a bacterium ultimately succeeds or fails in adapting to a new environment, it is essential to assess the temporal dynamics of its fitness over the course of colonization. The mammalian gut, into which exogenous microorganisms are regularly introduced, represents a biologically and clinically relevant system to explore microbial adaptational processes. In this study, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron, into the guts of germ-free mice to 1) determine whether the genetic requirements for colonization shift over time and, if so, 2) characterize the biological functions required for microbial survival at different points of colonization. The results of a high-throughput functional genetics assay (BarSeq), transcriptomics, and metabolomics converge on several conclusions. First, adaptation to the host gut occurs in distinct stages. We observed drastic changes in gene usage during the first week, shifting from high expression of amino acid biosynthesis to polysaccharide utilization genes. These changes were sustained thereafter, except for the continued upregulation of a single polysaccharide utilization locus responsible for the degradation of raffinose-family oligosaccharides rich in the standard chow diet fed to our mice. Spontaneous mutations in wildtype Bt also evolve around this locus, highlighting the importance of efficient carbohydrate metabolism in long-term persistence within a monoassociated gut. To improve microbiome-based therapies, it will be important to appreciate and meet the distinct needs of the organism during each stage of colonization.

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“…DNA barcoding systems have become especially influential to better understand microbial adaptive evolution. By taking advantage of amplicon sequencing methods to measure barcode frequency dynamics, these systems have been used with great success to directly observe evolutionary dynamics (30)(31)(32)(33), and identify selected mutations and the statistical patterns that characterize them (34)(35)(36)(37)(38)(39).…”

Section: Introduction 32mentioning

confidence: 99%

Quantifying the Local Adaptive Landscape of a Nascent Bacterial Community

Ascensao

Wetmore

Good

et al. 2022

Preprint

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The fitness effects of all possible mutations available to an organism largely shapes the dynamics of evolutionary adaptation. Tremendous progress has been made in quantifying the strength and abundance of selected mutations available to single microbial species in simple environments, lacking strong ecological interactions. However, the adaptive potential of strains that are part of multi-strain communities remains largely unclear. We sought to fill this gap for a stable community of two closely related ecotypes ("L" and "S") shortly after they emerged within the E. coli Long-Term Evolution Experiment (LTEE). To this end, we engineered genome-wide barcoded transposon libraries and developed a computational inference pipeline to measure the fitness effects of all possible gene knockouts in the coexisting strains as well as their ancestor, for many different conditions. We found that the fitness effect of most gene knockouts sensitively depends on the genetic background and the ecological conditions, as set by environmental perturbations and the relative frequency of both ecotypes. Despite the idiosyncratic behavior of individual knockouts, we still see consistent statistical patterns of fitness effect variation across both genetic background and community composition. The background dependence of mutational effects appears to reflect widespread changes in which gene functions are important for determining fitness, for all but the most strongly interacting genes. Additionally, fitness effects are correlated with evolutionary outcomes for a number of conditions, possibly revealing shifting patterns of adaptation. Together, our results reveal how ecological and epistatic effects combine to drive adaptive potential in recently diverged, coexisting ecotypes.

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Quantifying rapid bacterial evolution and transmission within the mouse intestine

Cited by 31 publications

References 45 publications

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Dynamic genetic adaptation of Bacteroides thetaiotaomicron murine gut colonization

Quantifying the Local Adaptive Landscape of a Nascent Bacterial Community

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