Biology subjects

Gandon, S.

Publications and source records attributed to Gandon, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolution of pathogen dormancy in fluctuating environments

Dormancy is a widespread life-history strategy that enables organisms to persist through periods of adverse environmental conditions. Despite its prevalence, the evolutionary forces shaping dormancy and the timing of reactivation remain poorly understood, particularly in pathogens facing predictable environmental fluctuations. Here, we investigate how seasonal variation can drive the joint evolution of pathogen dormancy and reactivation, and whether these traits are favoured to evolve as fixed or plastic strategies. Using a theoretical model of vector-borne disease transmission, we show when seasonality can promote plasticity in dormancy and reactivation. The optimal timing of transitions between active and dormant states depends critically on the environmental cues available to pathogens and on their reliability for predicting future transmission opportunities. Although motivated by the biology of relapsing malaria parasites, our results provide a general framework for understanding the evolution of dormancy as an adaptive response to periodic environmental fluctuations across diverse pathogen systems.

evolutionary biology↗

bioRxiv2026

The genome of the avian malaria parasite Haemoproteus majoris (lineage WW2) and its relationship to other Plasmodium species

Avian malaria parasites form a highly prevalent and genetically diverse group within the haemosporidians, yet they have long been overlooked relative to their human- and rodent-infecting counterparts. Among these, parasites of the genus Haemoproteus (Haemosporida, Haemoproteidae) are widespread and prevalent blood parasites of birds, transmitted by louse flies (Hippoboscidae) and biting midges (Ceratopogonidae). Recent phylogenomic analyses place Haemoproteus parasites at the root of the haemosporidian tree, making genomic data from these taxa essential for understanding the evolutionary origins of malaria parasites. To date, only two avian Plasmodium and one avian Haemoproteus genomes have been sequenced. We present the first assembled genome of Haemoproteus majoris (lineage WW2), a common blood parasite of passerine birds. As avian erythrocytes are nucleated, parasite DNA was enriched by FACS-based sorting to discriminate and isolate the parasite from host cell nuclei prior to whole-genome amplification. The genome was assembled using Nanopore long-read sequencing and polished with Illumina short-reads, yielding 145 contigs with a total assembly size of 23.9Mb and a G+C content of 27.85%. Genome annotation identified 5501 protein-coding genes, 69 non-coding RNA genes, and 57 long terminal repeat retrotransposons (LRT-RTs), including one full-length element. This genomic resource represents a critical step towards elucidating the evolutionary history and genomic architecture of avian malaria parasites. SIGNIFICANCE STATEMENTWe present the first assembled genome of Haemoproteus majoris (lineage WW2), a prevalent and generalist avian malaria parasite. Taxonomic resolution of this genus is difficult as there are few distinct morphological differences among closely-related species. This genome provides a valuable resource for studying the evolution within the Haemoproteus genus and to elucidate the evolutionary history of malaria parasites.

genomics↗

bioRxiv2025

The ambivalent effect of spatial structure on the spread of cooperative anti-CRISPR phages

Some phages have evolved the ability to cooperate to evade the immunity triggered by their bacterial host. A first exposure to the phage may weaken the host defences and allow later infections to be successful. Because this cooperation requires sequential infections, the phage can invade the host population only if its initial density is sufficiently high in a well-mixed environment. However, most natural bacterial populations are spatially structured. Could spatial structure create more favourable conditions for viral spread? Here we study the effect of spatial structure on the dynamics of cooperative anti-CRISPR (Acr) phages spreading in a population of CRISPR-Cas resistant Pseudomonas aeruginosa bacteria. We show experimentally that spatial structure does not always promote the spread of Acr-phages. In particular, the effect of spatial structure is modulated by the efficacy of the bacterial hosts CRISPR-Cas resistance and by the efficacy of the phage Acr protein. These results are discussed in the light of a mathematical model we developed to describe the spread of the phage. The model allows us to understand the ambivalent effects of spatial structure via its effects on the reproduction and on the persistence of the phage. More generally, we find that spatial structure can have opposite effects on the epidemiological dynamics of the phage, depending on the properties of the Acr protein encoded by the phage. This joint experimental and theoretical work yields a deeper understanding of the spatial dynamics of cooperative strategies in phages.

microbiology↗

bioRxiv2025

Single cell transcriptomics and development of gametocyte-specific molecular markers for avian malaria parasites

Avian malaria, caused by Plasmodium parasites, poses a significant threat to bird populations worldwide, particularly in vulnerable island ecosystems. Yet, progress in understanding avian malaria transmission dynamics has been hampered by the lack of molecular tools to quantify and sex the transmissible stages of the parasite: the male and female gametocytes. This challenge is compounded by the nucleated erythrocytes of avian hosts and the absence of an in vitro culture system, which have historically hindered the advancement of molecular approaches. Here, we develop and validate the first molecular markers to discriminate between asexual, male, and female gametocytes in the widespread avian malaria parasite Plasmodium relictum. Using single-cell RNA sequencing and orthology-guided stage mapping, we identified conserved, stage-specific transcripts and leveraged this information to develop molecular markers capable of quantifying and distinguishing male and female gametocytes in two parasite cyt-b lineages, pSGS1 and pDELURB. These markers outperformed microscopy in sensitivity, detected gametocytes earlier and for longer, and revealed consistently higher male-to-female gametocyte ratios than estimated by blood smears. The high degree of conservation of these markers across Plasmodium species suggests broad applicability of these markers to other avian lineages.

molecular biology↗

bioRxiv2025

Horizontal gene transfer, segregation loss and the speed of microbial adaptation

Microbial adaptation is driven by the circulation of mobile genetic elements (MGEs) among bacteria. On the one hand, MGEs can be viewed as selfish genes that spread like infectious diseases in a host population. On the other hand, the horizontal transfer and the loss of these MGEs is often viewed as a form of sexual reproduction that reshuffles genetic diversity in a way that may sometimes be adaptive for bacteria cells. Here, we show how these two perspectives can be reconciled using a single unified framework capturing the dynamics of multiple, interacting MGEs. We apply this framework to study how interactions between MGEs affecting rates of horizontal gene transfer and segregation loss shape the short- and long-term evolutionary dynamics of MGEs and the bacteria population. We show these interactions produce non-random MGE associations that can speed up or slow down microbial adaptation depending on the evolutionary conflicts between MGEs as well as between MGEs and their bacterial hosts. Moreover, we show how these interactions affect the evolutionary potential of the bacteria population. We discuss the implications of these predictions for the community response to environmental stressors such as antibiotic treatment or vaccination campaigns as well as the evolution of accessory genomes.

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↗

bioRxiv2024

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↗

bioRxiv2023

A multilocus perspective on the evolutionary dynamicsof multistrain pathogens

Many human pathogens, including malaria, dengue, influenza, Streptococcus pneumoniae, and cytomegalovirus, coexist as multiple genetically distinct strains. Understanding how these multistrain pathogens evolve is of critical importance for forecasting epidemics and predicting the consequences of vaccination. One factor believed to play an important role is naturally acquired immunity. Consequently, a large body of research has sought to predict how acquired immunity molds the genomics of pathogen populations (i.e., what shapes pathogen strain structure). The diversity of existing models has resulted in conflicting evolutionary predictions, and has sparked an ongoing debate about which predictions are most broadly applicable. Here, we adopt a multilocus population genetics perspective that unifies the predictions of existing models. We identify three key factors that determine the role of naturally acquired immunity in the evolution of pathogen strain structure: (i) the strength and specificity of immune protections, (ii) the dynamic immunological landscape, and (iii) the number of loci coding for the antigens of the pathogen. Isolating and discussing these three factors clarifies the relationship among previous models of multistrain dynamics, and establishes a solid theoretical foundation for the study of the evolutionary epidemiology of multistrain pathogens.

evolutionary biology↗

bioRxiv2023

Cities as parasitic burden? Malaria prevalence and diversity along an urbanization gradient in great tits

Urbanization is a worldwide phenomenon that modifies the environment. By affecting the reservoirs of pathogens and the body and immune conditions of hosts, urbanization alters the epidemiological dynamics and diversity of diseases. Cities could act as areas of pathogen dilution or amplification, depending on whether urban features have positive or negative effects on vectors and hosts. In this study, we focused on a host species and investigated the prevalence and diversity of avian malaria parasites (Plasmodium/Haemoproteus sp. and Leucocytozoon sp.) in great tits (Parus major) living across an urbanization gradient. In general, we observed high prevalence in adult birds (from 95% to 100%), yet lower prevalence in fledglings (from 0% to 38%). We found a slight tendency for increased Plasmodium sp. prevalence with increasing urbanization in adults. Urban nestlings had higher Plasmodium sp. infection rates than non-urban nestlings. We found evidence of higher diversity of parasites in the most natural urban park; however, parasite diversity was similar across other urbanization levels (e.g. from a little artificialized park to a highly anthropized industrial area). Parasite lineages were not habitat specific. Only one Plasmodium sp. lineage (YWT4) was associated with urban areas and some rare lineages (e.g., AFR065) were present only in a zoo area, perhaps because of the presence of African birds. This study suggests that urbanization can lead to a parasite amplification effect and can favor different avian malaria lineages.

ecology↗

bioRxiv2023

Eco-evolutionary feedbacks shape the evolution of constitutive and inducible defences

Organisms have evolved a range of constitutive (always active) and inducible (elicited by parasites) defence mechanisms, but we have limited understanding of what drives the evolution of these orthogonal defence strategies. Bacteria and their phages offer a tractable system to study this: bacteria can acquire constitutive resistance by mutation of the phage receptor (surface mutation, sm) or induced resistance through their CRISPR-Cas adaptive immune system. Using a combination of theory and experiments we demonstrate that the mechanism that establishes first has a strong advantage because it weakens selection for the alternative resistance mechanism. As a consequence, ecological factors that alter the relative frequencies at which the different resistances are acquired have a strong and lasting impact: high growth conditions promote the evolution of sm resistance by increasing the influx of receptor mutation events during the early stages of the epidemic, whereas a high infection risk during this stage of the epidemic promotes the evolution of CRISPR immunity, since it fuels the (infection-dependent) acquisition of CRISPR immunity. This work highlights the strong and lasting impact of the transient evolutionary dynamics during the early stages of an epidemic on the long-term evolution of constitutive and induced defences, which may be leveraged to manipulate phage resistance evolution in clinical and applied settings.

evolutionary biology↗

bioRxiv2023

Bacterial defences interact synergistically by disrupting phage cooperation

The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems1,2, with many bacteria carrying several systems3,4. In response, phages often carry counter-defence genes5-9. If and how bacterial defence mechanisms interact to protect against phages with counter-defence genes remains unclear. Here, we report the existence of a novel defence system, coined MADS (Methylation Associated Defence System), which is located in a strongly conserved genomic defence hotspot in Pseudomonas aeruginosa and distributed across Gram-positive and Gram-negative bacteria. We find that the natural co-existence of MADS and a Type IE CRISPR-Cas adaptive immune system in the genome of P. aeruginosa SMC4386 provides synergistic levels of protection against phage DMS3, which carries an anti-CRISPR (acr) gene. Previous work has demonstrated that Acr-phages need to cooperate to overcome CRISPR immunity, with a first sacrificial phage causing host immunosuppression to enable successful secondary phage infections10,11. Modelling and experiments show that the co-existence of MADS and CRISPR-Cas provides strong and durable protection against Acr-phages by disrupting their cooperation and limiting the spread of mutants that overcome MADS. These data reveal that combining bacterial defences can robustly neutralise phage with counter-defence genes, even if each defence on its own can be readily by-passed, which is key to understanding how selection acts on defence combinations and their coevolutionary consequences.

microbiology↗

bioRxiv2022

Effect of unequal vaccination coverage and migration on long-term pathogen evolution in a metapopulation

Worldwide inequalities in vaccine availability are expected to affect the spread and spatial distribution of infectious diseases. It is unclear, however, how spatial variation in vaccination coverage can affect the long-term evolution of pathogens. Here we use an analytical model and numerical simulations to analyse the influence of different imperfect vaccines on the potential evolution of pathogen virulence in a two-population model where vaccination coverage varies between populations. We focus on four vaccines, with different modes of action on the life-cycle of a pathogen infecting two host populations coupled by migration. We show that, for vaccines that reduce infection risk or transmissibility, spatial heterogeneity has little effect on pathogen prevalence and host mortality, and no effect on the evolution of pathogen virulence. In contrast, vaccines that reduce pathogen virulence can select for more virulent pathogens and may lead to the coexistence of different pathogen strains, depending on the degree of spatial heterogeneity in the metapopulation. This heterogeneity is driven by two parameters: pathogen migration and the difference in the vaccination rate between the two populations. We show that vaccines that only reduce pathogen virulence select mainly for a single pathogen strategy in the long term while vaccines that reduce both transmission and virulence can favor the coexistence of two pathogen genotypes. We discuss the implications and potential extensions of our analysis.

evolutionary biology↗

bioRxiv2022

Seasonality and the persistence of vector-borne pathogens

Many vector-borne diseases are affected by the seasonality of the environment. Yet, seasonality can act on distinct steps of the life-cycle of the pathogen and it is often difficult to predict the influence of the periodic fluctuations of the environment on the persistence of vector-borne pathogens. Here we analyse a general vector-borne disease model and we account for periodic fluctuations of different components of the pathogens life-cycle. We develop a perturbation analysis framework to obtain useful approximations to evaluate the overall consequences of seasonality on the persistence of pathogens. This analysis reveals when seasonality is expected to increase or to decrease pathogen persistence. We show that seasonality in vector density or in the biting rate of the vector can have opposite effects on persistence and we provide a useful biological explanation for this result based on the covariance between key compartments of the epidemiological model. This framework could be readily extended to explore the influence of seasonality on other components of the life cycle of vector-borne pathogens. Significance statementDoes seasonality increase or decrease the persistence of vector-borne diseases? The devil is in the details and our analysis shows that the effect of seasonality depends on which pathogen traits are affected by seasonality. We highlight the contrasting effects of seasonality in the abundance and/or in the biting rate of the vector on pathogen persistence.

ecology↗

bioRxiv2022

Phage-antibiotic synergy: cell filamentation is a key driver of successful phage predation

Phages are promising tools to fight antibiotic-resistant bacteria, and as for now, phage therapy is essentially performed in combination with antibiotics. Interestingly, combined treatments including phages and a wide range of antibiotics lead to an increased bacterial killing, a phenomenon called phage-antibiotic synergy (PAS), suggesting that antibiotic-induced changes in bacterial physiology alter the dynamics of phage propagation. Using single-phage and single-cell techniques, each step of the lytic cycle of phage HK620 was studied in E. coli cultures treated with either ciprofloxacin or cephalexin, two filamentation-inducing antibiotics. In the presence of sublethal doses of antibiotics, multiple stress tolerance and DNA repair pathways are triggered following activation of the SOS response. One of the most notable effects is the inhibition of bacterial division. As a result, a significant fraction of cells forms filaments that stop dividing but have higher rates of mutagenesis. Antibiotic-induced filaments become easy targets for phages due to their enlarged surface areas, as demonstrated by fluorescence microscopy and flow cytometry techniques. Adsorption, infection and lysis occur more often in filamentous cells compared to regular-sized bacteria. In addition, the reduction in bacterial numbers caused by impaired cell division may account for the faster elimination of bacteria during PAS. We developed a mathematical model to capture the interaction between sublethal doses of antibiotics and exposition to phages. This model shows that the induction of filamentation by sublethal doses of antibiotics can amplify the replication of phages and therefore yield PAS. We also use this model to study the consequences of PAS on the emergence of antibiotic resistance. A significant percentage of hyper-mutagenic filamentous bacteria are effectively killed by phages due to their increased susceptibility to infection. As a result, the addition of even a very low number of bacteriophages produced a strong reduction of the mutagenesis rate of the entire bacterial population. We confirm this prediction experimentally using reporters for bacterial DNA repair. Our work highlights the multiple benefits associated with the combination of sublethal doses of antibiotics with bacteriophages.

microbiology↗

bioRxiv2022

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↗

bioRxiv2022

Evolution and spread of multidrug resistant pathogens in a spatially heterogeneous environment

The emergence and the spread of multi-adapted pathogens is often viewed as a slow process resulting from the incremental accumulation of single adaptations. In bacteria, for instance, multidrug resistance to antibiotics may result from the sequential acquisition of single drug resistance to different antibiotics. In phytopathogens, the ability to infect different resistant varieties of crops may also result from the accumulation of distinct virulence genes. Here we use a general epidemiological model to analyse the evolution of pathogen adaptations throughout an epidemic spreading in a heterogeneous host population where selection varies periodically in space. This spatially heterogeneous selection may result from the use of different drugs, different vaccines or different crop varieties in agriculture. We study both the transient evolution of pathogen adaptation at the front of the epidemic and the long-term evolution far behind the epidemic front. We identify five different types of epidemic profiles that may arise from different combinations of spatial heterogeneity and the cost of multi-adaptation. In particular, we show that multi-adaptation can drive epidemic spread, while the evolution of single-adaptation may only occur in a second phase, when the pathogen specializes on local selective pressures. Indeed, a generalist pathogen with multiple adaptations can outpace the spread of a coalition of specialist pathogens when selection varies frequently in space. This result is amplified in finite host populations because demographic stochasticty can lead to the extinction of maladapted pathogens specialised to a local selective pressure. Our work has important implications for the management of multiple drugs and vaccines against pathogens but also for the optimal deployment of resistant varieties in agriculture.

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↗