Horizontal gene transfer overrides mutation in
            <i>Escherichia coli</i>
            colonizing the mammalian gut

Frazão, Nelson; Sousa, Ana; Lässig, Michael; Gordo, Isabel

doi:10.1073/pnas.1906958116

Cited by 140 publications

(156 citation statements)

References 54 publications

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“…Furthermore, while a lot of attention has been placed on the rates of homologous recombination in the chromosome of the species, it is now clear that HGT drives the evolution of virulence 12, 42, 68, 69 and antibiotic resistance 70–72 in pathogenic strains as well as that of many other traits in commensal strains 12 . For example, MGEs were recently shown to be more important than point mutations for the colonization of the mouse gut by E. coli commensals 73 . Here, we aimed at providing a global picture of the evolution of the E. coli genomes with an emphasis on the variation of gene repertoires in strains from a variety of sources (environmental and geographic) across a single continent.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli

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Amandine

Sousa

et al. 2020

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23Escherichia coli is a commensal of birds and mammals, including humans. It can act as an 24 opportunistic pathogen and is also found in water and sediments. Since most population 25 studies have focused on clinical isolates, we studied the phylogeny, genetic diversification, 26 and habitat-association of 1,294 isolates representative of the phylogenetic diversity of more 27 than 5,000, mostly non-clinical, isolates originating from humans, poultry, wild animals and 28 water sampled from the Australian continent. These strains represent the species diversity 29 and show large variations in gene repertoires within sequence types. Recent gene transfer is 30 driven by mobile elements and determined by habitat sharing and by phylogroup 31 membership, suggesting that gene flow reinforces the association of certain genetic 32 backgrounds with specific habitats. The phylogroups with smallest genomes had the highest 33 rates of gene repertoire diversification and fewer but more diverse mobile genetic elements, 34 suggesting that smaller genomes are associated with higher, not lower, turnover of genetic 35 information. Many of these small genomes were in freshwater isolates suggesting that some 36 lineages are specifically adapted to this environment. Altogether, these data contribute to 37 explain why epidemiological clones tend to emerge from specific phylogenetic groups in the 38 presence of pervasive horizontal gene transfer across the species. 39 40 circulation of strains and the high plasticity of their genomes have not erased the 68 associations of certain clades with certain isolation sources. In consequence, such 69 associations might reflect local adaptation 16,45 , which would suggest frequent genetic 70 interactions between the novel adaptive changes and the strains' genomic background. 71Understanding how the evolution of gene repertoires is shaped by population structure and 72 habitats requires large-scale comparative genomics of samples with diverse sources of 73 isolation representative of natural populations of E. coli. Most of the efforts of genome 74 sequencing have been devoted to study pathogenic lineages and very few genomic data are 75 available for commensal strains, especially in wild animals, and environmental strains. Here, 76we analysed the genomes of a large collection of E. coli strains collected across many 77 human, domestic and wild animal and environmental sources in different geographic 78 locations from the Australian continent. This collection is dominated by non-clinical isolates, 79 corresponding to the main habitats of the species. We sought to understand the dynamics of 80 the evolution of gene repertoires and how it was driven by mobile genetic elements. The 81 analysis of the isolation sources in the light of phylogenetic structure and genome variation 82 suggests that adaptation varies with the habitat and the phylogenomic background. This 83 contributes to explain why known epidemiological clones of the species emerge from specific 84 phylogenetic groups, even though virulen...

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Section: Discussionmentioning

confidence: 99%

Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli

Touchon

Amandine

Sousa

et al. 2020

Preprint

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“…All mice were co-colonised with the triple mutant at a lower starting frequency (10%), as this carries more beneficial mutations and has a higher fitness under the 7-day streptomycin treatment (S1 Fig). Throughout the entire experiment, both strains coexisted in all mice, and E. coli generally maintained a population size of >10 7 colony-forming units (CFU)/g of faeces (S1 Fig), i.e., the typical size of its ecological niche in this host [41].…”

Section: Emergence and Maintenance Of Mutation Rate Variation In A Gumentioning

confidence: 99%

“…After divergence from their common ancestor, the mutators acquired potentially adaptive mutations in the cad operon, ycbC, atoC, psuK/fruA and fruB, and tdcA/tdcR. Of these targets, mutations in the last two have previously been observed during adaptation of E. coli to the gut of immune-competent or immunocompromised mice [40,41]. Many of the adaptive targets are functionally important for regulating carbon (dgoR, frlR, atoC, and, potentially, the cad operon) [77,[83][84][85] or nitrogen metabolism (ptsP and tdcA/tdcR) [79,86,87], stress resistance (ptsP, cad operon, ycbC, and, potentially, atoC), and peptidoglycan biogenesis (ycbC) [77,[83][84][85].…”

Section: Adaptive Mutations Target Metabolism and Stress Resistancementioning

confidence: 99%

Low mutational load and high mutation rate variation in gut commensal bacteria

et al. 2020

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Bacteria generally live in species-rich communities, such as the gut microbiota. Yet little is known about bacterial evolution in natural ecosystems. Here, we followed the longterm evolution of commensal Escherichia coli in the mouse gut. We observe the emergence of mutation rate polymorphism, ranging from wild-type levels to 1,000-fold higher. By combining experiments, whole-genome sequencing, and in silico simulations, we identify the molecular causes and explore the evolutionary conditions allowing these hypermutators to emerge and coexist within the microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III proofreading and catalytic subunits, which increase mutation rate by approximately 1,000-fold and stabilise hypermutator fitness, respectively. Strong mutation rate variation persists for >1,000 generations, with coexistence between lineages carrying 4 to >600 mutations. The in vivo molecular evolution pattern is consistent with fitness effects of deleterious mutations s d � 10 −4 /generation, assuming a constant effect or exponentially distributed effects with a constant mean. Such effects are lower than typical in vitro estimates, leading to a low mutational load, an inference that is observed in in vivo and in vitro competitions. Despite large numbers of deleterious mutations, we identify multiple beneficial mutations that do not reach fixation over long periods of time. This indicates that the dynamics of beneficial mutations are not shaped by constant positive Darwinian selection but could be explained by other evolutionary mechanisms that maintain genetic diversity. Thus, microbial evolution in the gut is likely characterised by partial sweeps of beneficial mutations combined with hitchhiking of slightly deleterious mutations, which take a long time to be purged because they impose a low mutational load. The combination of these two processes could allow for the longterm maintenance of intraspecies genetic diversity, including mutation rate polymorphism. These results are consistent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we have identified key evolutionary processes shaping the genetic composition of this community.

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“…In complete bacterial genomes from isolates, higher frequency of prophages is also observed in the gut (Anthenelli et al , 2020). The gut-associated temperate phages mediate bacterial colonization dynamics in mouse models (Reyes et al , 2013; Frazão et al , 2019), and their distribution patterns have been associated with the presence of severe acute malnutrition (Reyes et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

Quantification of lysogeny caused by phage coinfections in microbial communities from biophysical principles

Luque

Silveira

2020

Preprint

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19Temperate phages can integrate in their bacterial host genome to form a lysogen, often 20 modifying the phenotype of the host. Lysogens are dominant in the microbial-dense 21 environment of the mammalian-gut. This observation contrasts with the long-standing 22 hypothesis of lysogeny being favored in microbial communities with low densities. Here we 23 hypothesized that phage coinfections-the most studied molecular mechanism of lysogeny 24 in lambda phage-increases at high microbial abundances. To test this hypothesis, we 25 developed a biophysical model of coinfection and stochastically sampled ranges of phage 26 and bacterial concentrations, adsorption rates, lysogenic commitment times, and 27 community diversity from marine and gut microbiomes. Based on lambda experiments, a 28 Poisson process assessed the probability of lysogeny via coinfection in these ecosystems. In 29 90% of the sampled marine ecosystems, lysogeny stayed below 10% of the bacterial 30 community. In contrast, 25% of the sampled gut communities stayed above 25% of 31 lysogeny, representing an estimated nine trillion lysogens formed via phage coinfection in 32 the human gut every day. The prevalence of lysogeny in the gut was a consequence of the 33 higher densities and faster adsorption rates. In marine communities, which were 34 characterized by lower densities and phage adsorption rates, lysogeny via coinfection was 35 still possible for communities with long lysogenic commitments times. Our study suggests 36 that physical mechanisms can favor coinfection and cause lysogeny at poor growth 37 conditions (long commitment times) and in rich environments (high densities and 38 adsorption rates).39 40 3 Importance 41 42Phage integration in bacterial genomes manipulate microbial dynamics from the oceans to 43 the human gut. This phage-bacteria interaction, called lysogeny, is well-studied in 44 laboratory models, but its environmental drivers remain unclear. Here we quantified the 45 frequency of lysogeny via phage coinfection-the most studied mechanism of lysogeny-by 46 developing a biophysical model that incorporated a meta-analysis of the properties of 47 marine and gut microbiomes. Lysogeny was found to be more frequent in high-productive 48 environments like the gut, due to higher phage and bacterial densities and faster phage 49 adsorption rates. At low cell densities, lysogeny via coinfection was possible for hosts with 50 long duplication times. Our research bridges the molecular understanding of lysogeny with 51

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Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut

Cited by 140 publications

References 54 publications

Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli

Phylogenetic background and habitat drive the genetic diversification ofEscherichia coli

Low mutational load and high mutation rate variation in gut commensal bacteria

Quantification of lysogeny caused by phage coinfections in microbial communities from biophysical principles

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