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Blanquart, F.

Publications and source records attributed to Blanquart, F..

At least 19 recordsLinked to original sources

Quantifying the mechanisms of vaccine-induced serotype replacement in Streptococcus pneumoniae using genome-informed modelling

Streptococcus pneumoniae is a colonizer of the childs nasopharynx and a leading cause of invasive pneumococcal disease (IPD). Despite widespread use of pneumococcal conjugate vaccines, recent rebounds in IPD incidence have coincided with serotype replacement. Whether this phenomenon is driven by the replacement of serotypes within lineages or the replacement of the lineages themselves is unclear. Here, we quantified the relative contribution of these two mechanisms to serotype replacement in carriage and their consequences for IPD. We combined nationwide longitudinal surveillance of carriage and IPD in children from 2002 to 2023 with whole-genome sequencing. Observed lineage-specific carriage rates across PCV-related periods were fitted with polynomial logistic regression and compared with two counterfactual scenarios, each isolating one mechanism with: (i) fixed serotype composition within varying lineages and (ii) serotype shifts within fixed lineage carriage rates over time. Carriage dynamics were consistent with an 82% contribution of serotype shifts within persistent lineages. Estimates of serotype-specific IPD incidence derived from this predominant scenario correlated with observed IPD trends. These findings quantify the dominant role of serotype replacement within persistent lineages, disentangling the vaccine-driven adaptive history of S. pneumoniae.

microbiology↗

The analysis of a large dataset of PCR-test results in the community reveals the impact of age, variants and vaccination status on SARS-CoV-2 viral dynamics

The COVID-19 pandemic has shown the value of large-scale community PCR tests for epidemic surveillance, but the viral load measurements they provide have seldom been exploited to reconstruct within-host trajectories. Because these data are collected for diagnostic rather than research purposes, they are characterized by sparse longitudinal follow-up, heterogeneous sampling, and missing metadata, raising uncertainty about their usefulness to reconstruct with-host viral dynamics. We first conducted a simulation study to assess the feasibility of estimating the viral dynamics patterns from such datasets. Across multiple scenarios replicating realistic sampling patterns, we found that peak viral load and clearance time could be estimated with good accuracy, although uncertainty tended to be underestimated. Parameters driving early viral kinetics, e.g. incubation and proliferation time, were mostly estimated with poor precision, as most community tests are conducted after symptom onset, later in infection. We then applied this framework to a large dataset of 322,218 PCR tests associated with symptomatic SARS-CoV-2 infections in France between July 2021 and March 2022, encompassing both Delta-variant circulation and the emergence of first Omicron variants. We quantified the effects of age, vaccination, and variants on viral load trajectories. Age [≥]65 years was consistently associated with longer clearance time, extending the duration of detectable viral load by 2 to 6 days. Vaccination shortened the clearance time by 2 to 4 days but had minimal impact on peak viral load. Infections by Omicron-variants were associated with a lower peak viral load and shorter clearance times compared with pre-Omicron (Delta) infections. Thus, community PCR tests can be leveraged to identify key parameters of viral dynamics. As multiplex PCR testing becomes increasingly widespread, establishing robust frameworks for data collection, sharing, and privacy protection will be essential to support the use of these data. Author SummaryIn this study, we explored whether viral load data collected routinely in community laboratories can help us understand how factors like age, vaccination, and viral variant influence the course of infection. These data, collected for diagnostic purposes rather than research, are large but often incomplete, with most individuals tested only after the time of symptoms onset. We first used simulations to assess whether, despite these limitations, key aspects of viral dynamics can be reliably estimated. We then applied our approach to millions of test results collected in France during periods dominated by Delta and Omicron variants. We found that older age was consistently associated with longer infection duration, while vaccination reduced the time the virus remained detectable without affecting peak viral levels. Omicron infections were generally associated with lower peak viral load and somewhat faster clearance than pre-Omicron infections. Overall, our work demonstrates that community testing data, can provide valuable insights into viral dynamics and help monitor the effects of new variants or interventions. As multiplex tests become more common, facilitating and improving data collection, sharing, and privacy protection will be essential to make the most of these resources in future outbreaks.

systems biology↗

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↗

Quantifying the effects of antibiotic resistance and within-host competition on strain fitness in Streptococcus pneumoniae

Competition plays a key role in shaping the structure and diversity of bacterial populations. In many clinically important bacterial species, strains compete at multiple scales: at the between-host scale for new hosts to colonise, and at the within-host scale during co-colonisation. Characterising these multiple facets of competition plays an important role in understanding bacterial ecology. This is particularly relevant for antibiotic resistance, where competition between antibiotic-susceptible and resistant strains determines resistance dynamics. In this work, we perform survival analyses on a large longitudinal dataset of Streptococcus pneumoniae carriage to quantify how within-host competition affects the rates of clearance and establishment of pneumococcal strains. We find that the presence of a within-host competitor is associated with a 33% increase in clearance and a 54% reduction in establishment. Priority effects and serotype differences partially predict the outcomes of this within-host competition. Further, we quantify the effects of antibiotic resistance on betweenand within-host components of fitness. Antibiotic consumption is associated with increased clearance rate for both susceptible and resistant strains, albeit to a higher extent in susceptible strains. In the absence of antibiotics, we find some evidence that resistance is associated with increased susceptibility to within-host competition, suggesting a fitness cost of resistance. Overall, our work provides quantitative insights into pneumococcal competition across scales and the role of this competition in shaping pneumococcal epidemiology.

ecology↗

Persistent, Private and Mobile genes: a model for gene dynamics in evolving pangenomes

The pangenome of a species is the set of all genes carried by at least one member of the species. In bacteria, pangenomes can be much larger than the set of genes carried by a single organism. Many questions remain unanswered regarding the evolutionary forces shaping the patterns of presence/absence of genes in pangenomes of a given species. We introduce a new model for bacterial pangenome evolution along a species phylogeny that explicitly describes the timing of appearance of each gene in the species and accounts for three generic types of gene evolutionary dynamics: persistent genes that are present in the ancestral genome, private genes that are specific to a given clade, and mobile genes that are imported once into the gene pool and then undergo frequent horizontal gene transfers. We call this model the Persistent-Private-Mobile (PPM) model. We develop an algorithm fitting the PPM model and apply it to a dataset of 902 Salmonella enterica genomes. We show that the best fitting model is able to reproduce the global pattern of some multivariate statistics like the gene frequency spectrum and the parsimony vs. frequency plot. Moreover, the gene classification induced by the PPM model allows us to study the position of accessory genes on the chromosome depending on their category, as well as the gene functions that are most present in each category. This work paves the way for a mechanistic understanding of pangenome evolution, and the PPM model developed here could be used for dynamics-aware gene classification.

evolutionary biology↗

Evolution of Virulence in Emerging Epidemics: From Theory to Experimental Evolution and Back

The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage {lambda} spreading in continuous cultures of Escherichia coli. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis - including calculations of the selection gradients - and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage {lambda}. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.

evolutionary biology↗

Lessons from twenty years of the life of commensal Escherichia coli populations in a human gut

Escherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary commensal niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli isolates from 22 stools sampled during a 20-year period from a healthy man (ED) living in Paris, France. All phylogroups, except C, were represented, with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty-five clones were identified based on their haplogroup and pairwise genomic single nucleotide polymorphism distance and classified in three phenotypes according to their abundance and residence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four over five dominant/resident clones belonged to B2 and closely related F phylogroups, whereas sub-dominant/transient clones belonged mainly to B1, A and D phylogroups. The long residence times of B2 clones seemed to be counterbalanced by lower colonization abilities. Clones with larger within-host frequency persisted for longer in the host. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, we identified ED-specific genomic properties including a set of genes involved in a metabolic pathway (mhp cluster) and a very rare antiviral defense island. The E. coli colonization within the gut microbiota was shaped by both the intrinsic properties of the strain lineages, in particular longer residence of phylogroup B2, and the environmental constraints such as diet or phages.

microbiology↗

Persistence-colonization trade-off and niche differentiation enable the coexistence of E. coli phylogroups

Despite extensive literature on the pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal in healthy hosts. Based on two detailed longitudinal datasets on the gut microbiota of healthy adult individuals followed over months to years in France and in the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and the ability to remain in the host (residence). Major E. coli lineages (phylogroups) exhibited similar fitness but a diversity of strategies, from strong colonizers residing for a few days in the gut, to poor colonizers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity resided for longest in hosts. Moreover, the residence time of a strain was reduced more strongly when it competed with other strains of the same phylogroup than of different phylogroups, suggesting niche differentiation between them. To investigate the consequences of the trade-off and niche differentiation for coexistence between strains, we developed a discrete-state Markov model describing the dynamics of E. coli in a population of hosts. We found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms enabling the coexistence of phylogroups over extended periods of time. Our model predicted that a reduction in transmission (e.g. better hygiene) would not alter the balance between phylogroups, while disturbance of the microbiome (e.g. antibiotics) would hinder residents strains such as those of the extra-intestinal pathogenic phylogroup B2.3.

evolutionary biology↗

Within-host density and duration of colonization of multidrug-resistant Enterobacterales acquired during travel to the tropics

Although it seems obvious that antibiotic use promotes antibiotic resistance, the processes underlying the changes in prevalence of MRE in European communities are still poorly understood. Information on how the within-host bacterial density varies after acquisition of a resistant strain and in the absence of antibiotic selection is key to our ability to further understand, model and manage resistance in the community. Empirical studies on the within-host dynamics following colonization by MRE are very scarce. Here, we study the within-host strain dynamics in healthy travelers colonized with MRE upon their return from tropical regions. Densities of both sensitive and resistant strains are stable for a few months, until resistant strains are abruptly cleared. Multivariate survival analysis further revealed that MRE acquired from Asia and carried at larger densities persist for longer. These dynamics do not support the classically assumed slow competitive exclusion of MRE. Rather, MRE and sensitive strains coexist in apparent equilibrium for months, with MRE representing about 0.1% of total Enterobacterales, before MRE are abruptly cleared. These results inform potential therapeutic strategies to clear MRE and epidemiological models of antibiotic resistance.

microbiology↗

Stochastic within-host dynamics of antibiotic resistance: Resistant survival probability, size at the end of treatment and carriage time after treatment

The use of an antibiotic may lead to the emergence and spread of bacterial strains resistant to this antibiotic. Experimental and theoretical studies have investigated the drug dose that minimizes the risk of resistance evolution over the course of treatment of an individual, showing that the optimal dose will either be the highest or the lowest drug concentration possible to administer; however, no analytical results exist that help decide between these two extremes. To address this gap, we develop a stochastic mathematical model of bacterial dynamics under antibiotic treatment. We explore various scenarios of density regulation (bacterial density affects cell birth or death rates), and antibiotic modes of action (biostatic or biocidal). We derive analytical results for the survival probability of the resistant subpopulation until the end of treatment, the size of the resistant subpopulation at the end of treatment, the carriage time of the resistant subpopulation until it is replaced by a sensitive one after treatment, and we verify these results with stochastic simulations. We find that the scenario of density regulation and the drug mode of action are important determinants of the survival of a resistant subpopulation. Resistant cells survive best when bacterial competition reduces cell birth and under biocidal antibiotics. Compared to an analogous deterministic model, the population size reached by the resistant type is larger and carriage time is slightly reduced by stochastic loss of resistant cells. Moreover, we obtain an analytical prediction of the antibiotic concentration that maximizes the survival of resistant cells, which may help to decide which drug dosage (not) to administer. Our results are amenable to experimental tests and help link the within and between host scales in epidemiological models.

evolutionary biology↗

The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans

Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostics, prevention and treatment is still lacking. We used a collection of 1282 BSI and commensal E. coli isolates collected in France over a 17-year period (2000-2017) and we compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity increased steadily from 23% in 1980 to 46% in 2010. Together our findings imply that E. coli exhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.

microbiology↗

Bottlenecks can constrain and channel evolutionary paths

Population bottlenecks are commonplace in experimental evolution, specifically in serial passaging experiments where microbial populations alternate between growth and dilution. Natural populations also experience such fluctuations caused by seasonality, resource limitation, or host-to-host transmission for pathogens. Yet, how unlimited growth with periodic bottlenecks influence the adaptation of populations is not fully understood. Here we study theoretically the effects of bottlenecks on the accessibility of evolutionary paths and on the rate of evolution. We model an asexual population evolving on a minimal fitness landscape consisting of two types of beneficial mutations with the empirically supported trade-off between mutation rate and fitness advantage, in the regime where multiple beneficial mutations may segregate simultaneously. In the limit of large population sizes and small mutation rates, we show the existence of a unique most likely evolutionary scenario, determined by the size of the wild-type population at the beginning and at the end of each cycle. These two key demographic parameters determine which adaptive paths may be taken by the evolving population by controlling the supply of mutants during growth and the loss of mutants at the bottleneck. We do not only show that bottlenecks act as a deterministic control of evolutionary paths but also that each possible evolutionary scenario can be forced to occur by tuning demographic parameters. This work unveils the effects of demography on adaptation of periodically bottlenecked populations and can guide the design of evolution experiments.

genetics↗

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↗

Genetic determinism of phage-bacteria coevolution in natural populations

Coevolution between bacteriophage (or phage) and their bacterial host is thought to be key for the coexistence of these antagonists. Recent studies have revealed the major role of mobile genetic elements in the emergence of phage resistant hosts but how phage escape these defenses in the wild remained to be explored. Here we show a striking parallel in phage evolving counter defenses to host defenses in natural population. We established a large collection of phages and their bacterial hosts and we explored the genetic structure of their interaction. We find that clearly delineated genomic clusters of phage are specific for distinct clades within a bacterial species, Vibrio crassostreae, yet while all phages can adsorb, only a subset of hosts are killed due to intracellular defense mechanisms. Host genomes contain multiple mobile defense genes and susceptibility to phage is negatively correlated with genome size. Phages also display extensive gene content variation, but their genome size remains conserved. We show that this gene content variation in hosts and phage is due to rapid turnover of genes involved in defense and escape, and that by exchanging anti-defense genes, phages irreversibly switch host. This could be indicative of co-evolution following the matching-allele-model of specificity and the spatial and temporal variability of phage infectivity further suggests that negative-frequency dependent selection drives phage-vibrio coevolutionary dynamics. We propose a "pan-escape system" that can be shared among phages by homologous recombination within a population that infects a bacterial host.

microbiology↗

Epidemiological dynamics of bacteriocin competition and antibiotic resistance

Bacteriocins, toxic peptides involved in the competition between bacterial strains, are extremely diverse. Previous work on bacteriocin dynamics has highlighted the role of non-transitive rock-paper-scissors competition in maintaining the coexistence of different bacteriocin profiles. The focus to date has primarily been on bacteriocin interactions at the within-host scale. Yet, in species such as Streptococcus pneumoniae with relatively short periods of colonisation and limited within-host diversity, ecological outcomes are also shaped by processes at the epidemiological (between-host) scale. Here, we first investigate bacteriocin dynamics and diversity in epidemiological models. We find that in these models, bacteriocin diversity is more readily maintained than in within-host models, and with more possible combinations of coexisting bacteriocin profiles. Indeed, maintenance of diversity in epidemiological models does not require rock-paper-scissors dynamics; it can also occur through a competition-colonisation trade-off. Second, we investigate the link between bacteriocin diversity and diversity at antibiotic resistance loci. Previous work has proposed that bacterial duration of colonisation modulates the fitness of antibiotic resistance. Due to their inhibitory effects, bacteriocins are a plausible candidate for playing a role in the duration of colonisation episodes. We extend the epidemiological model of bacteriocin dynamics to incorporate an antibiotic resistance locus and demonstrate that bacteriocin diversity can indeed maintain the coexistence of antibiotic sensitive and resistant strains.

evolutionary biology↗

Evolution of virulence in emerging epidemics: inference from an evolution experiment

Inference using mathematical models of infectious disease dynamics is a powerful tool to analyse epidemiological data and elucidate pathogen life cycles. Key epidemiological parameters can be estimated from demographic time series by computing the likelihood of alternative models of pathogen transmission. Here we use this inference approach to analyze data from an evolution experiment in which we monitored both the epidemiology and the evolution of the temperate bacteriophage{lambda} during an epidemic. We estimate parameter values for all the life-history traits of two distinct strains of the virus. In particular, we estimate the ability of the two virus strains to modulate plastically the rate of lysogenization with the multiplicity of infection. Our work illustrates how inference from experimental evolution data can feedback on the development of models aiming to predict the epidemiology and evolution of infectious diseases.

evolutionary biology↗

Success of Escherichia coli O25b:H4 ST131 clade C associated with a decrease in virulence

Escherichia coli of sequence type (ST) 131 resistant to fluoroquinolones and producer of CTX-M-15 is globally one of the major extraintestinal pathogenic E. coli (ExPEC). ST131 phylogenesis showed that multidrug-resistant ST131 strains belong to a clade called C, descending from an ancestral clade called B, comprising mostly antibiotic-susceptible strains. Antibiotic resistance could appear as one of the keys of the clade C global success. We hypothesized that other features of ST131 clade C could contribute to this success since other major global ExPEC clones (ST73, ST95) are mostly antibiotic-susceptible. To test this hypothesis, we measured the growth abilities, early biofilm formation and virulence-factor content of a collection of clade B and clade C strains. Moreover, using competition assays, we measured the capacity of selected representative strains of clades B and C to colonize the mouse intestine and urinary tract, and to kill mice in a septicemia model. Clade B and C strains had similar growth ability. However, clade B strains were more frequently early biofilm producers, expressed mostly faster their type 1 fimbriae and displayed more virulence factor-encoding genes than clade C strains. Clade B outcompeted clade C in the gut and/or urinary tract colonization models and in the septicemia model. These results strongly suggest that clade C strain evolution includes a loss of virulence, i.e. a process that could enhance micro-organism persistence in a given host and thus optimize transmission. This process, associated with acquired antibiotic-resistance, could ensure clade C strain survival in environments under antibiotic pressure.\n\nImportanceExtraintestinal pathogen Escherichia coli (ExPEC) are virulent but mostly antibiotic-susceptible. One worrying exception is ST131, a major multidrug resistant ExPEC clone that has spread worldwide since the 2000s. To contain the emergence of this threatening clone, we need to understand what factors favored its emergence and dissemination. Here, we investigated whether multidrug-resistant ST131 had advantageous phenotypic properties beyond multidrug resistance. To this end, we competed the emergent multidrug-resistant ST131 with its antibiotic-susceptible ancestor in different conditions: biofilm production, in vivo colonization and virulence experiments. In all in vivo competitions, we found that multidrug-resistant ST131 was losing to its ancestor, suggesting a lesser virulence of multidrug-resistant ST131. It was previously described that losing virulence can increase micro-organism persistence in some populations and subsequently its level of transmissibility. Thus, a decreased level of virulence, associated with multidrug resistance, could explain the global success of ST131.

microbiology↗

How does habitat choice affect evolutionary rescue in subdivided populations?

Evolutionary rescue is the process by which a population, in response to an environmental change, successfully avoids extinction through adaptation. In spatially structured environments, dispersal can affect the probability of rescue. Here, we model an environment consisting of patches that degrade one after another, and we investigate the probability of rescue by a mutant adapted to the degraded habitat. We focus on the effects of dispersal and of immigration biases. We find that the probability of evolutionary rescue can undergo up to three phases: (i) starting from low dispersal rates, it increases with dispersal; (ii) at intermediate dispersal rates, it decreases; (iii) finally, at large dispersal rates, the probability of rescue increases again with dispersal, except if mutants are too counter-selected in not-yet-degraded patches. The probability of rescue is generally highest when mutant and wild-type individuals preferentially immigrate into patches that have already undergone environmental change. Additionally, we find that mutants that will eventually rescue the population most likely first appear in non-degraded patches, and that the relative contribution of standing genetic variation vs. de-novo mutations declines with increasing emigration rates. Overall, our results show that habitat choice, when compared to the often studied unbiased immigration scheme, can substantially alter the dynamics of population survival and adaptation to new environments.

evolutionary biology↗