Biology subjects

Tenaillon, O.

Publications and source records attributed to Tenaillon, O..

14 recordsLinked to original sources

bioRxiv2026

High-resolution lineage tracking maps the multi-phase evolution and adaptive potential of biofilms

Although biofilms represent the dominant bacterial lifestyle and are major contributors to recalcitrant, treatment-resistant infections, their evolutionary dynamics at the individual lineage resolution remain poorly understood. We combine DNA barcoding-mediated lineage tracking and spatial sampling of > 100,000 lineages of Escherichia coli to characterize sequential phases of biofilm evolution quantitatively. Severe founder effects during surface colonization initially reduce the effective population size by nearly three orders of magnitude, establishing significant spatial segregation. This structure is subsequently eroded by a previously underappreciated secondary migration phase, during which cells released upon perturbation recolonize biofilms with a rate 103-fold higher than naive planktonic cells. Adaptive evolution subsequently drives specialization through mutations targeting these distinct stages of the biofilm life cycle. Under severe antibiotic bottlenecks, active secondary migration continuously resuscitates local lineage diversity, enabling the parallel emergence of resistance across hundreds of independent lineages. Once locally established, migration drives a rapid spatial spread of resistant mutants. Together, these findings reveal how spatial segregation and secondary migration shape biofilm dynamics, coupling short-term ecological resilience with long-term adaptive potential.

microbiology↗

bioRxiv2026

Collective protection drives human gut microbiota response to amoxicillin treatment.

The gut microbiota is central to human health, contributing to nutrient processing, metabolite production and protection against pathogens. Yet it is also an unintended target of antibiotic treatments, particularly after oral administration. Antibiotic exposure can therefore disrupt community structure, leading to dysbiosis and promoting the selection of resistant bacteria. Although studies in patients and animal models have shown that these effects vary markedly between individuals, host-related factors have made it difficult to isolate the specific contribution of the microbiota itself. Here, we used a controlled in vitro gut model (MBRA) to examine how 16 human gut microbiotas from the NutriNet-Sante cohort respond to the widely prescribed {beta}-lactam amoxicillin (AMX). By combining dense temporal sampling, 16S amplicon sequencing and mass spectrometry, we observed highly heterogeneous response trajectories, ranging from near-stable communities to strong but reversible disruptions. These differences were not only reflected in the final magnitude of perturbation, but also in the timing, pace and recovery of microbiota change during treatment. Initial community composition partly structured these responses, as Lachnospiraceae/Bacteroidaceae ratio strongly correlated with perturbation. Dynamic quantification of AMX further showed that microbiotas differed in their capacity to deplete the drug over time, thereby altering the duration of exposure above critical concentration thresholds. Supplementation with clavulanic acid that inhibits {beta}-lactamases confirmed that this process was largely mediated by {beta}-lactamase activity. Finally, microbiotas displaying rapid AMX depletion showed reduced selection of resistant Enterobacteriaceae. Together, our results indicate that both initial community composition and the temporal dynamics of antibiotic inactivation jointly determine microbiota resilience and resistance selection.

microbiology↗

bioRxiv2026

Dietary emulsifiers and host inflammation synergistically drive genomic evolution of Crohn disease-associated E. coli toward enhanced pathogenicity

Background and AimsThe rising incidence of Crohns disease (CD) in Westernized countries has been linked to changes in diet and increased consumption of food additives, yet the mechanisms by which these factors fuel intestinal inflammation remain unclear. Adherent-invasive Escherichia coli (AIEC), a pathobiont involved in CD pathogenesis, lacks a clear genetic hallmark but exhibits intestinal colonization and virulence traits, raising questions about the evolutionary forces promoting its emergence among select individuals. Here, we investigated how chronic exposure to two common dietary emulsifiers, carboxymethylcellulose (CMC) and polysorbate 80 (P80), along with host inflammation, drives AIEC genomic evolution and pathogenic potential. MethodsWild-type and Il10-deficient mice were monocolonized with AIEC and chronically exposed to CMC, P80, or water. Bacterial isolates were collected and analyzed for genomic diversification, mutations, and phenotype both in vitro and in vivo. ResultsEmulsifiers accelerated AIEC genomic diversification and selected for mutations linked to increased motility, invasion, and pro-inflammatory activity. Moreover, dietary emulsifier-evolved strains displayed a marked fitness advantage in vivo, outcompeting their counterparts in murine hosts, with the greatest advantage observed when evolution occurred under inflammatory conditions. Notably, evolutionary pathways and phenotypic outcomes were shaped by both emulsifier and the hosts inflammatory status, highlighting synergy between diet and host genetics in fostering pro-inflammatory pathobionts. ConclusionThese findings provide an evolutionary framework connecting modern dietary habits to the emergence of pathogenic AIEC strains, and underscore the importance of dietary interventions in individuals at risk for inflammatory bowel disease.

microbiology↗

bioRxiv2026

Linking Codon- and Protein-Level Mutation Scores to Population Genetics Reveals Heterogeneous Selection Efficiency Across Escherichia coli Lineages

Quantifying the selective effects of individual mutations is essential to understand how their population-wise frequencies evolve under natural selection and genetic drift. Large genomic datasets provide a real-life experiment that we exploit to characterize the efficiency of selection across different mutations types and populations. Using Direct Coupling Analysis, a model from statistical physics, we derive protein-informed scores for individual non-synonymous mutations identified in 81,440 Escherichia coli genomes. We show that these scores act as a latent variable capturing the probability that a mutation is beneficial, neutral, or mildly to highly deleterious. We contribute to the debate on the importance of synonymous mutations by demonstrating that their selection intensities span a single order of magnitude in the E. coli species, whereas non-synonymous mutations span six orders of magnitude. We further relate selection efficiency to genetic drift, defined as the inverse of population size, and to ecological lifestyle, and we identify a 10,000-fold reduction in selection efficiency between the entire E. coli species and its most pathogenic populations. Together, these results highlight how population genetics and protein variant fitness predictors inform one another: variation in selection efficiency is associated with shifts in the distribution of mutation scores, and population genetics data provide a benchmark to assess the accuracy of these scores. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/711857v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@c9f62borg.highwire.dtl.DTLVardef@140b8d9org.highwire.dtl.DTLVardef@27cf00org.highwire.dtl.DTLVardef@18722b9_HPS_FORMAT_FIGEXP M_FIG Schematic representation of the analysis of polymorphism in 81,440 Escherichia coli genomes. 458,443 polymorphic codon sites were identified and oriented using homologous sequences from closely related species. Mutations can be classified as synonymous or non-synonymous based on whether they alter the amino-acid sequence encoded, and real-valued scores predictive of fitness effects can be attributed to mutations within each of these classes. Codon scores reflect the global codon usage preference within the E. coli genome. DCA scores capture position- and amino-acid-specific preference as well as epistatic constraints and are obtained for each protein from a set of distantly related homologous sequences. Coupled with the abundance of polymorphic sites within different E. coli subpopulations, these different polymorphism classifications allow to precisely compare the intensity of selection between different types of mutations and across populations with distinct lifestyles, illustrated here by their pathogenic power. C_FIG

genetics↗

bioRxiv2025

Evidence for Neolithic acquisition of the high pathogenic island by Escherichia coli followed by recent selection

Many genetic elements involved in virulence and pathogenicity have been identified in commensal bacteria that are also opportunistic pathogens, but how these elements evolve is less well known. Understanding the evolutionary history of virulence elements requires genomes sampled in commensalism in healthy hosts, as genomes from bacterial infections are biased towards higher pathogenicity. Here, using a rare collection of human commensal Escherichia coli sampled in France from 1980 to 2020, we inferred the evolutionary history of the High Pathogenicity Island (HPI), a key virulence factor of E. coli with an uncertain evolutionary origin. The most likely scenario implied a horizontal transfer of the HPI from Yersinia pestis/pseudotuberculosis to the Enterobacterales, including E. coli, [~]4,700 years ago, coinciding with a period of increased population densities and human-animal interactions. The element subsequently spread in E. coli, with signs of positive epistasis with phylogroups B2 and F, and was positively selected in the last 100 years. Our work sheds light on the history and mode of evolution of virulence in an important opportunistic pathogen. It suggests the Neolithic period may have favored not only the emergence of zoonotic pathogens but also gene transfer between bacterial species, enriching the gene repertoire of major pathogens with potentially important implications on public health nowadays. Significance statement"Pathogenicity islands" are groups of genes that can be gained and lost on the chromosome of bacterial species and make them more pathogenic and virulent, but their evolutionary origin is unknown. We studied the origin and evolution of the High Pathogenicity Island of the major opportunistic pathogen Escherichia coli using molecular dating and phylogenetic analyses on very large genomic databases. We found that this island likely transferred from Yersinia pestis/pseudotuberculosis to E. coli 4,000 years ago, a period of increased population densities and intensified human-animal interactions, and was positively selected in the last 100 years. Thus, the origin of virulence can trace back to exchanges of mobile genetic elements that may be favored by particular circumstances in human history and have important consequences on human health nowadays.

evolutionary biology↗

bioRxiv2025

High-Throughput Conjugation Reveals Strain Specific Recombination Patterns Enabling Precise Trait Mapping in Escherichia coli

Genetic exchange is a cornerstone of evolutionary biology and genomics, driving adaptation and enabling the identification of genetic determinants underlying phenotypic traits. In Escherichia coli, horizontal gene transfer via conjugation and transduction not only promotes diversification and adaptation but has also been instrumental in mapping genetic traits. However, the dynamics and variability of bacterial recombination remain poorly understood, particularly concerning the patterns of recombined DNA fragments. To elucidate these patterns and simultaneously develop a tool for trait mapping, we designed a high-throughput conjugation method to generate recombinant libraries. Recombination profiles were inferred through whole-genome sequencing of individual clones and populations after selection of a marker from the donor strain in the recipient. This analysis revealed an extraordinary range of recombined fragment sizes, spanning less than ten kilobases to over a megabase--a pattern that varied across the three tested strains. Mathematical modelling indicated that this diversity in recombined fragment size enables precise identification of selected loci following genetic crosses. Consistently, population sequencing pinpointed a selected marker at kilobase-scale accuracy, offering a robust tool for identifying subtle genetic determinants that could include point mutations in core genes. These findings challenge the conventional view that conjugation always transfers large fragments, suggesting that even short recombined segments, traditionally attributed to transduction, may originate from conjugation.

microbiology↗

bioRxiv2025

The evolution of robustness and fragility during long-term bacterial adaptation

Most mutations affecting fitness are harmful, and their inevitable occurrence reduces mean population fitness. Theory predicts that well-adapted populations may evolve mechanisms to minimize this deleterious load. Direct selection to increase mutational robustness can be achieved in the laboratory. However, its spontaneous evolution during general adaptation remains uncertain, with mixed evidence across model systems. Here, we studied the effects of highly pleiotropic point mutations in Escherichia coli over a 15,000-generation adaptive trajectory. The fitness effects of both beneficial and deleterious mutations were attenuated with increased adaptation over time. In contrast, pleiotropic effects in new environments became more severe and widespread with greater adaptation. These results show that trade-offs between robustness and fragility can rapidly evolve in regulatory networks, regardless of whether driven by adaptive or non-adaptive processes. More broadly, these results show that adaptation can generate a hidden potential for phenotypic diversity, unpredictably shaping evolutionary prospects in new environments.

evolutionary biology↗

bioRxiv2022

The evolution of fitness effects during long-term adaptation in bacteria

The distribution of fitness effects of new mutations is central to predicting adaptive evolution, but observing how it changes as organisms adapt is challenging. Here we use saturated, genome-wide insertion libraries to quantify how the fitness effects of new mutations changed in two E. coli populations that adapted to a constant environment for 15,000 generations. The proportions of neutral and deleterious mutations remained constant, despite large fitness gains. In contrast, the beneficial fraction declined rapidly, approximating an exponential distribution, with strong epistasis profoundly changing the genetic identity of adaptive mutations. Despite this volatility, many important targets of selection were predictable from the ancestral distribution. This predictability occurs because genetic target size contributed to the fixation of beneficial mutations as much as or more than their effect sizes. Overall, our results demonstrate that short-term adaptation can be idiosyncratic but empirically predictable, and that long-term dynamics can be described by simple statistical principles. One-Sentence SummaryCouce et al. demonstrate that short-term bacterial adaptation is predictable at the scale of individual genes, while long-term adaptation is predictable at a global scale.

evolutionary biology↗

bioRxiv2022

Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes

Characterizing the effect of mutations is key to understand the evolution of protein sequences and to separate neutral amino-acid changes from deleterious ones. Epistatic interactions between residues can lead to a context dependence of mutation effect. Context dependence constrains the amino-acid changes that can contribute to polymorphism in the short term, and the ones that can accumulate between species in the long term. We use computational approaches to accurately predict the polymorphisms segregating in a panel of 61,157 Escherichia coli genomes from the analysis of distant homologues. By comparing a context-aware Direct-Coupling Analysis modelling to a non-epistatic approach, we show that the genetic context strongly constrains the tolerable amino acids in 30% to 50% of amino-acid sites. The study of more distant species suggests the gradual build-up of genetic context over long evolutionary timescales by the accumulation of small epistatic contributions.

evolutionary biology↗

bioRxiv2021

Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1

Epistasis affects genome evolution together with our ability to predict individual mutation effects. The mechanistic basis of epistasis remains, however, largely unknown. To quantify and better understand interactions between fitness-affecting mutations, we focus on a 11 amino-acid -helix of the protein {beta}-lactamase TEM-1, and build a comprehensive library of more than 15,000 double mutants. Analysis of the growth rates of these mutants shows pervasive epistasis, which can be largely explained by a non-linear two-state model, where inactivating, destabilizing, neutral, or stabilizing mutations additively contribute to the phenotype. Hence, most epistatic interactions can be predicted by a non-linear model informed by single-point mutational measurements only. Deviations from the two-state model are consistently found for few pairs of residues, in particular when they are in contact. This result, as well as single-point mutation parameters, can be quantitatively found back through direct-coupling-analysis-based statistical models inferred from homologous sequence data. Our results thus shed light on the existence and the origins of the multiple determinants of the epistatic landscape, even at the level of small structural components of a protein, and suggest that the corresponding constraints shape the entire {beta}-lactamase family.

evolutionary biology↗

bioRxiv2021

The population genomics of increased virulence and antibiotic resistance in human commensal Escherichia coli over 30 years in France

Escherichia coli is a commensal species of the lower intestine, but also a major pathogen causing intestinal and extra-intestinal infections, increasingly prevalent and resistant to antibiotics. Most studies on genomic evolution of E. coli used isolates from infections. Here instead, we whole-genome sequenced a collection of 403 commensal E. coli isolated from fecal samples of healthy adult volunteers in France (1980-2010). These isolates were distributed mainly in phylogroups A and B2 (30% each) and belonged to 152 sequence types (STs), the five most frequent being ST10 (phylogroup A) (16.3%), ST73 and ST95 (phylogroup B2) (6.3 and 5.0%, respectively), ST69 (phylogroup D) (4.2%) and ST59 (phylogroup F) (3.9%), and 224 O:H serotypes. ST and serotype diversity increased over time. The O1, O2, O6 and O25-groups used in bioconjugate O-antigen vaccine against extra-intestinal infections were found in 23% of the strains of our collection. The increase in frequency of virulence-associated genes and antibiotic resistances was driven by two evolutionary mechanisms. Evolution of virulence gene frequency was driven by both clonal expansion of STs with more virulence genes ("ST-driven") and increases in gene frequency within STs independently of changes in ST frequencies ("gene-driven"). In contrast, the evolution of resistance was dominated by increases in frequency within STs ("gene-driven"). This study provides a unique picture of the phylogenomic evolution of E. coli in its human commensal habitat over 30 years and will have implications for the development of preventive strategies. IMPORTANCEEscherichia coli is an opportunistic pathogen with the greatest burden of antibiotic resistance, one of the main causes of bacterial infections and an increasing concern in an ageing population. Deciphering the evolutionary dynamics of virulence and antibiotic resistance in commensal E. coli is important to understand adaptation and anticipate future changes. The gut of vertebrates is the primary habitat of E. coli and probably where selection for virulence and resistance take place. Unfortunately, most whole-genome sequenced strains are isolated from pathogenic conditions. Here, we whole genome sequenced 403 E. coli commensals isolated from healthy French subjects on a 30-year period. Virulence genes increased in frequency by both clonal expansion of clones carrying them and increases in frequency within clones whereas resistance genes increased by within clone increased frequency. Prospective studies of E. coli commensals should be performed worldwide to have a broader picture of evolution and adaptation of this species.

genomics↗

bioRxiv2019

The role of mutational spectrum in the selection against mutator alleles

Rapidly adapting microbe and cancer cell populations often evolve high mutation rates. Yet, once adaptive opportunity declines, antimutator alleles are expected to take over as a result of indirect selection against deleterious mutations. Theory indicates that the most important determinant of antimutator invasions is the extent of mutation rate reduction. However, inconsistent results from evolution experiments suggest that additional factors may also play a major role in antimutator dynamics. Here we show that the idiosyncratic mutation bias exhibited by different mutators - a previously unrecognized factor - can greatly alter mutator susceptibility to antimutator invasions. Using a simulation model calibrated to mimic a well-known long-term evolution experiment with bacteria, we show that differences in average deleterious load can account for order-of-magnitude changes in antimutator fitness for a realistic range of parameters. Since these parameters are known to vary with the environment, our results reveal an unanticipated source of variability in antimutator dynamics. Finally, we estimated the genome-wide average disruptive effect on proteins of mutations caused by different mutators, and found marked and systematic differences emerging across mutators and species with different genomic GC compositions. Taken together, our results suggest that antimutator dynamics may be highly dependent on the specific genetic, ecological and evolutionary history of a given population. Such dependence reveals a more complex picture than anticipated, being relevant for understanding mutators in clinical settings, as well as how hypermutability shapes the evolution of bacterial genome size and composition.

evolutionary biology↗

bioRxiv2018

The molecular basis of genetic interaction diversity in a metabolic pathway

Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by the dependence of their effects on the genetic background and environment. Even when molecular interactions between genes are known, it is unclear how these translate to organism-level interactions between alleles. We therefore characterized the interplay of genetic and environmental dependencies in determining fitness by quantifying ~4,000 fitness interactions between expression variants of two metabolic genes, in different environments. We detect a remarkable variety of environment-dependent interactions, and demonstrate they can be quantitatively explained by a mechanistic model accounting for catabolic flux, metabolite toxicity and expression costs. Complex fitness interactions between mutations can therefore be predicted simply from their simultaneous impact on a few connected molecular phenotypes.

genetics↗

bioRxiv2016

Accumulation of deleterious mutations during bacterial range expansions

Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present 3-4 times fewer mutations. Estimation of the distribution of fitness effect (DFE) under a spatially explicit model reveals a mean negative effect for new mutations (-0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, we show that the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines remained unchanged. Our results thus suggest that successful expanding species are affected by deleterious mutations that accumulate during the expansion process, leading to a drastic impairment of their evolutionary potential.

evolutionary biology↗