Biology subjects

Guillemet, M.

Publications and source records attributed to Guillemet, M..

7 recordsLinked to original sources

bioRxiv2026

Bacterial strain structure shapes the trajectory of antibiotic resistance genes from plasmid to chromosome

The evolutionary dynamics determining whether an antimicrobial resistance (AMR) gene resides on a plasmid or a chromosome are critical to understanding the spread of resistance. While theoretical models often predict that beneficial traits should ultimately integrate into the more stable chromosome, contemporary genomic data frequently shows a strong enrichment of resistance genes on mobile, yet costly and less stable plasmids. Here, we propose that the widespread plasmid-mediated resistance observed today may not represent a stable evolutionary equilibrium, but rather a snapshot of an ongoing process. Using a stochastic multi-strain model, we explore the role of strain diversity as a determinant of the timescale of this process. We suggest that the population structure of the bacterial host species, maintained by balancing selection, acts as a substantial barrier to the selective sweep of vertically transmitted chromosomal genes. Because horizontal transmission allows conjugative plasmids to readily cross these strain boundaries, our model indicates that plasmid-borne resistance can transiently dominate the population before chromosomal integration takes over, and that this transient dominance can last for decades. We illustrate these predictions by analysing antimicrobial resistance gene location in three common opportunistic gut pathogens. Furthermore, we show how extending the model to include co-selection between resistance genes on multi-drug resistance plasmids can lead to more complex dynamics that transiently reverse this plasmid-to-chromosome trajectory. Overall, our findings highlight how bacterial population structure can dictate the evolutionary trajectory of beneficial genes, suggesting that the current distribution of AMR genes between chromosome and plasmids is a prolonged transient state rather than a static endpoint.

evolutionary biology↗

bioRxiv2025

Emergent epistasis mediates the role of negative frequency-dependent selection in bacterial strain structure

Strain structure is a well-documented phenomenon in many pathogenic and commensal bacterial species, where distinct strains persist over time exhibiting stable associations between genetic or phenotypic traits. This structure is surprising, particularly in highly recombinogenic species like Streptococcus pneumoniae, because recombination typically breaks down linkage disequilibrium, the non-random association of alleles at different loci. Allelic diversity is a necessary condition of strain structure. Recent work suggests that multi-locus negative frequency-dependent selection (NFDS) acts to maintain diversity across bacterial genomes. Here, using modelling and genomic analysis, we show that multi-locus NFDS also shapes bacterial strain structure through emergent epistatic effects. We develop models of two NFDS mechanisms - metabolic niche differentiation and competition-colonisation trade-offs - and show that epistasis emerges readily in these models. Notably, both models generate frequency-dependent epistasis. Unlike classical epistasis, this acts to either reinforce or abolish existing strain structure, making observed allele associations contingent on the evolutionary history of the population. We then use a dataset of over 3000 S. pneumoniae genomes to test our model predictions, and make observations consistent with emerging epistatic effects on gene associations. Our results extend and generalise previous work on the role of antigen-specific acquired immunity (a diversity-maintaining mechanism) on strain structure. Overall, this works contributes to a better understanding of the evolutionary processes shaping the structure of bacterial populations, which is central to predictive modelling of multi-strain pathogens

evolutionary biology↗

bioRxiv2025

Host Competitive Asymmetries Accelerate Viral Evolution in a Microbe-Virus Coevolutionary System

Microbial host populations evolve traits conferring specific resistance to viral predators via various defense mechanisms, while viruses reciprocally evolve traits to evade these defenses. Such co-evolutionary dynamics often involve diversification promoted by negative frequency-dependent selection. However, microbial traits conferring competitive asymmetries can induce directional selection, opposing diversification. Despite extensive research on microbe-virus co-evolution, the combined effect of both host trait types and associated selection remains unclear. Using a CRISPR-mediated co-evolutionary system, we examine how the co-occurrence of both trait types impacts viral evolution and persistence, previously shown to be transient and non-stationary in computational models. A stochastic model incorporating host competitive asymmetries via variation of intrinsic growth rates reveals that competitively-advantaged host clades generate the majority of immune diversity. Greater asymmetries extend viral extinction times, accelerate viral adaptation locally in time, and augment long-term local adaptation. These findings align with previous experiments, and provide further insights into long-term co-evolutionary dynamics.

evolutionary biology↗

bioRxiv2024

Transient evolutionary epidemiology of viral adaptation and lethal mutagenesis

Beneficial mutations drive the within-host adaptation of viral populations and can prolong the duration of host infection. Yet, most mutations are not adaptive and the increase of the mean fitness of viral populations is hampered by deleterious and lethal mutations. Because of this ambivalent role of mutations, it is unclear if a higher mutation rate boosts or slows down viral adaptation. Here we study the interplay between selection, mutation, genetic drift and within-host dynamics of viral populations. We obtain good approximations for the transient evolutionary epidemiology of viral adaptation under the assumption that the mutation rate is high and the effects of non-lethal mutations remain small. We use this theoretical framework to discuss the feasibility of lethal mutagenesis to treat viral infections in the light of quantitative predictions we obtained for the critical mutation rates of a range of different viruses.

evolutionary biology↗

bioRxiv2023

Chance favors the prepared genomes: horizontal transfer shapes the emergence of antibiotic resistance mutations in core genes.

Bacterial lineages vary in the frequency with which they acquire novel traits, like antibiotic resistance or virulence. While previous studies have highlighted the impact of the genetic background on the successful acquisition of novel traits through horizontal gene transfer, the impact of the latter on the subsequent evolution of bacterial genomes by point mutations remains poorly understood. Here, we studied the evolution of resistance to quinolones in thousands of Escherichia coli genomes. Resistance-conferring point mutations in the core genes are frequent and accumulate very quickly. We searched for gene gains and losses significantly associated with the subsequent acquisition of these resistance mutations. This revealed 60 groups of genes in genetic linkage whose gain or loss induced a change in the probability of subsequently becoming resistant to quinolones by point mutations in gyrA and parC. Although some of these chronologies may reflect epidemiological trends, most of these groups encoded functions that were previously associated with antibiotic resistance, tolerance, or persistence, often specifically under quinolone treatment. A lot of the largest groups were found in prophages or plasmids, and they usually increased the likelihood of subsequent resistance mutations. Conversely groups of lost genes were typically small and chromosomal. Quinolone resistance was among the first resistances acquired in the extant lineages of E. coli and its acquisition was associated with an increased likelihood of acquiring other types of resistances, including to aminoglycosides and beta-lactams. Our findings suggest that gene flow shapes the subsequent fixation rate of adaptive mutations in core genes. Given the substantial gene flow within bacterial genomes, interactions between horizontal transfer and point mutations in core genes may be key to the success of adaptation processes.

evolutionary biology↗

bioRxiv2022

Building pyramids against the evolutionary emergence of pathogens

Mutations allowing pathogens to escape host immunity promote the spread of infectious diseases in heterogeneous host populations and can lead to major epidemics. Understanding the conditions favoring these evolutionary emergences is key for the development of durable control strategies against pathogens. Here we compare the durability of three different control strategies: (i) a mixing strategy where the host population results from the mix of two single-resistant genotypes, (ii) a pyramiding strategy where host resistance is due to a single double-resistant genotype, (iii) a combining strategy where host resistance is due to a mix between a single-resistant genotype and a double-resistant genotype. First, we use evolutionary epidemiology theory to clarify the interplay between demographic stochasticity and evolutionary dynamics to show that the pyramiding strategy always yields lower probability of evolutionary emergence. Second, we confirm experimentally these predictions using virulent bacteriophages introduced in bacterial populations where we can manipulate the diversity and the depth of CRISPR immunity. Our work shows that pyramiding multiple defenses into the same individual host and avoiding mixing with single-defense strategies is a robust way to protect individuals and populations against pathogen evolutionary emergence. These results have practical implications for the optimal deployment of host resistance in agriculture and biotechnology but also for the optimal use of vaccination against human pathogens.

evolutionary biology↗

bioRxiv2021

Competition and coevolution drive the evolution and the diversification of CRISPR immunity

The diversity of resistance challenges the ability of pathogens to spread and to exploit host populations [1-3]. Yet, how this host diversity evolves over time remains unclear because it depends on the interplay between intraspecific competition among host genotypes and coevolution with pathogens. Here we study experimentally the effect of coevolving phage populations on the diversification of bacterial CRISPR immunity across space and time. We demonstrate that the negative-frequency-dependent selection generated by coevolution is a powerful force that maintains host resistance diversity and selects for new resistance mutations in the host. We also find that host evolution is driven by asymmetries in competitive abilities among different host genotypes. Even if the fittest host genotypes are targeted preferentially by the evolving phages they often escape extinctions through the acquisition of new CRISPR immunity. Together, these fluctuating selective pressures maintain diversity, but not by preserving the pre-existing host composition. Instead, we repeatedly observe the introduction of new resistance genotypes stemming from the fittest hosts in each population. These results highlight the importance of competition on the transient dynamics of host-pathogen coevolution.

microbiology↗