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Nicot, A.

Publications and source records attributed to Nicot, A..

3 recordsLinked to original sources

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

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

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