Biology subjects

Gandon, S.

Publications and source records attributed to Gandon, S..

8 recordsLinked to original sources

bioRxiv2018

To block or not to block: the adaptive manipulation of plague transmission

The ability of the agent of plague, Yersinia pestis, to form a biofilm blocking the gut of the flea has been considered to be a key evolutionary step in maintaining flea-borne transmission. However, blockage decreases dramatically the life expectancy of fleas, challenging the adaptive nature of blockage. Here we develop an epidemiological model of plague that accounts for its different transmission routes, as well as the within-host competition taking place between bacteria within the flea vector. We use this theoretical framework to identify the environmental conditions promoting the evolution of blockage. We also show that blockage is favored at the onset of an epidemic, and that the frequencies of bacterial strains exhibiting different strategies of blockage can fluctuate in seasonal environments. This analysis quantifies the contribution of different transmission routes in plague and makes testable predictions on the adaptive nature of blockage.\n\nSignificance statementPlague transmission relies on the ability of infected fleas to inoculate Y. pestis bacteria to vertebrate hosts. The production of a biofilm by the bacteria blocks the forgut of the flea and increases infectivity. But the adaptive nature of blockage remains controversial because it has a massive survival cost on the infected fleas and reduces dramatically the length of the infection: an extreme form of the classical virulence-transmission tradeoff. Here we develop a comprehensive model of the multiple routes of plague transmission, we determine when blockage can be viewed as an adaptive manipulation of its flea vector and we generate several testable predictions on the evolution of plague in both endemic and epidemic situations.

evolutionary biology↗

bioRxiv2018

Evolution of specialization in heterogeneous environments: equilibrium between selection, mutation and migration

Adaptation in spatially heterogeneous environments results from the balance between local selection, mutation and migration. We study the interplay among these different evolutionary forces and demography in a classical two habitat scenario with asexual reproduction. We develop a new theoretical approach that fills a gap between the restrictive assumptions of Adaptive Dynamics and Quantitative Genetics. This analysis yields more accurate predictions of the equilibrium phenotypic distribution in different habitats. We examine the evolutionary equilibrium under general conditions where demography and selection may be non-symmetric between the two habitats. In particular we show how migration may increase differentiation in a source-sink scenario. We discuss the implications of these analytic results for the adaptation of organisms with large mutation rates such as RNA viruses.

evolutionary biology↗

bioRxiv2018

Evolutionary emergence of infectious diseases in heterogeneous host populations

Emergence and re-emergence of pathogens are notoriously difficult to predict. The erratic nature of those events is reinforced by the stochastic nature of pathogen evolution during the early phase of an epidemic. For instance, mutations allowing pathogens to escape host resistance may boost pathogen spread and promote emergence. Yet, the ecological factors that govern such evolutionary emergence remain elusive both because of the lack of ecological realism of current theoretical frameworks and the difficulty of experimentally testing their predictions. Here we develop a theoretical model to explore the effects of the heterogeneity of the host population on the probability of pathogen emergence, with or without pathogen evolution. We show that evolutionary emergence and the spread of escape mutations in the pathogen population is more likely to occur when the host population contains an intermediate proportion of resistant hosts. We also show that lower pathogen inoculum size and higher diversity of host resistance decrease the probability of evolutionary emergence. Crucially, we present experimental confirmations of these predictions using lytic bacteriophages infecting their bacterial hosts containing diverse CRISPR-Cas immune defenses. We discuss the implications of these results for cross-species spillover and for the management of emerging infectious diseases.\n\nSignificance statementCan we predict the emergence of infectious diseases? The probability that an epidemic breaks out is highly dependent on the ability of the pathogen to acquire new adaptive mutations and to induce evolutionary emergence. Forecasting pathogen emergence thus requires a good understanding of the interplay between epidemiology and evolution taking place at the onset of an outbreak. Here, we provide a comprehensive theoretical framework to analyze the impact of host population heterogeneity on the probability of pathogen evolutionary emergence. We use this model to predict the impact of the fraction of susceptible hosts, the inoculum size of the pathogen and the diversity of host resistance on pathogen emergence. Our experiments using lytic bacteriophages and CRISPR-resistant bacteria support our theoretical predictions.

evolutionary biology↗

bioRxiv2018

Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity

Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage taking down the host CRISPR-Cas immune system to allow a second Acr- phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points towards higher phage densities. Collectively these data help to understand how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.\n\nHighlightsO_LIBacteria with CRISPR immunity remain partially resistant to Acr-phage\nC_LIO_LISequentially infecting Acr phages cooperate to overcome CRISPR resistance\nC_LIO_LIAcr-phage epidemiology depends on the initial phage density\nC_LIO_LICRISPR resistant bacteria can drive Acr phages extinct\nC_LI\n\neTOC blurbSome phages encode Acr proteins that block bacterial CRISPR-Cas immune systems. Although CRISPR-Cas can clear the first infection, this Acr-phage still suppresses the host immune system, which can be exploited by other Acr-phages. This is critical for Acr-phage amplification, but this \"cooperation\" only works beyond a critical Acr-phage density threshold.

microbiology↗

bioRxiv2018

Timing malaria transmission with mosquito fluctuations

Temporal variations in the activity of arthropod vectors can dramatically affect the epidemiology and evolution of vector-borne pathogens. Here we explore the \"Hawking hypothesis\" stating that these pathogens may evolve the ability to time investment in transmission to match the activity of their vectors. First, we use a theoretical model to identify the conditions promoting the evolution of time-varying transmission strategies in pathogens. Second, we experimentally test the \"Hawking hypothesis\" by monitoring the within-host dynamics of Plasmodium relictum throughout the acute and the chronic phases of the bird infection. To explore the periodicity in the host parasite density, we develop a new methodology to correct for non-stationarities in the host parasitaemia. We detect a periodic increase of parasitaemia and mosquito infection in the late afternoon that coincides with an increase in the biting activity of its natural vector. We also detect a positive effect of mosquito bites on Plasmodium replication in the birds both in the acute and in the chronic phases of the infection. This study highlights that Plasmodium parasites use two different strategies to increase the match between transmission potential and vector availability. We discuss the adaptive nature of these unconditional and plastic transmission strategies with respect to the time-scale and the predictability of the fluctuations in the activity of the vector.\n\nImpact SummarySeasonal and daily fluctuations in the environment affect the abundance and the activity of vectors and may therefore have profound consequences on the transmission of infectious diseases. Here we show that, in accord with evolutionary theory, malaria parasites have evolved two different and complementary strategies to cope with fluctuations in mosquito availability. First, Plasmodium relictum adopts an unconditional strategy whereby within-host parasitaemia and mosquito infection increases in the afternoon and in the evening, when its vector, the Culex pipiens mosquito, is most active. Second, we find evidence for a plastic strategy allowing the parasitaemia to rapidly increase after exposure to mosquito bites.

evolutionary biology↗

bioRxiv2017

Pathogen evolution: slow and steady spreads the best

The theory of life history evolution provides a powerful framework to understand the evolutionary dynamics of pathogens in both epidemic and endemic situations. This framework, however, relies on the assumption that pathogen populations are very large and that one can neglect the effects of demographic stochasticity. Here we expand the theory of life history evolution to account for the effects of finite population size on the evolution of pathogen virulence. We show that demographic stochasticity introduces additional evolutionary forces that can qualitatively affect the dynamics and the evolutionary outcome. We discuss the importance of the shape of pathogen fitness landscape and host heterogeneity on the balance between mutation, selection and genetic drift. In particular, we discuss scenarios where finite population size can dramatically affect classical predictions of deterministic models. This analysis reconciles Adaptive Dynamics with population genetics in finite populations and thus provides a new theoretical toolbox to study life-history evolution in realistic ecological scenarios.

evolutionary biology↗

bioRxiv2017

Evolution and manipulation of vector host choice

The transmission of many animal and plant diseases relies on the behavior of arthropod vectors. In particular, the choice to feed on either infected or uninfected hosts can dramatically affect the epidemiology of vector-borne diseases. I develop an epidemiological model to explore the impact of host choice behavior on the dynamics of these diseases and to examine selection acting on vector behavior, but also on pathogen manipulation of this behavior. This model identifies multiple evolutionary conflicts over the control of this behavior and generates testable predictions under different scenarios. In general, the vector should evolve the ability to avoid infected hosts. However, if the vector behavior is under the control of the pathogen, uninfected vectors should prefer infected hosts while infected vectors should seek uninfected hosts. But some mechanistic constraints on pathogen manipulation ability may alter these predictions. These theoretical results are discussed in the light of observed behavioral patterns obtained on a diverse range of vector-borne diseases. These patterns confirm that several pathogens have evolved conditional behavioral manipulation strategies of their vector species. Other pathogens, however, seem unable to evolve such complex conditional strategies. Contrasting the behavior of infected and uninfected vectors may thus help reveal mechanistic constraints acting on the evolution of the manipulation of vector behavior.

evolutionary biology↗

bioRxiv2016

Complete avian malaria parasite genomes reveal host-specific parasite evolution in birds and mammals

Avian malaria parasites are prevalent around the world, and infect a wide diversity of bird species. Here we report the sequencing and analysis of high quality draft genome sequences for two avian malaria species, Plasmodium relictum and Plasmodium gallinaceum. We identify 50 genes that are specific to avian malaria, located in an otherwise conserved core of the genome that shares gene synteny with all other sequenced malaria genomes. Phylogenetic analysis suggests that the avian malaria species form an outgroup to the mammalian Plasmodium species and using amino acid divergence between species, we estimate the avian and mammalian-infective lineages diverged in the order of 10 million years ago. Consistent with their phylogenetic position, we identify orthologs of genes that had previously appeared to be restricted to the clades of parasites containing P. falciparum and P. vivax - the species with the greatest impact on human health. From these orthologs, we explore differential diversifying selection across the genus and show that the avian lineage is remarkable in the extent to which invasion related genes are evolving. The subtelomeres of the P. relictum and P. gallinaceum genomes contain several novel gene families, including an expanded surf multigene family. We also identify an expansion of reticulocyte binding protein homologs in P. relictum and within these proteins, we detect distinct regions that are specific to non-human primate, humans, rodent and avian hosts. For the first time in the Plasmodium lineage we find evidence of transposable elements, including several hundred fragments of LTR-retrotransposons in both species and an apparently complete LTR-retrotransposon in the genome of P. gallinaceum.

genomics↗