Biology subjects

van Houte, S.

Publications and source records attributed to van Houte, S..

21 records · Page 2Linked to original sources

bioRxiv2019

Exploitation of the cooperative behaviours of anti-CRISPR phages

Many bacteria encode CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-associated) adaptive immune systems to protect themselves against their viruses (phages)1. To overcome resistance, phages have evolved anti-CRISPR proteins (Acr), which naturally vary in their potency to suppress the host immune system and avoid phage extinction2,3,4,5. However, these Acr-phages need to cooperate in order to overcome CRISPR-based resistance4,5: while many initial infections by Acr-phages are unsuccessful, they nonetheless lead to the production of Acr proteins, which generate immunosuppressed cells that can be successfully exploited by other Acr-phages in the population4,5. Here we test the prediction that phages lacking acr genes (Acr-negative phages) may exploit this cooperative behaviour6. We demonstrate that Acr-negative phages can indeed benefit from the presence of Acr-positive phages during pairwise competitions, but the extent of this exploitation depends on the potency of the Acr protein. Specifically, \"strong\" Acr proteins are more exploitable and benefit both phage types, whereas \"weak\" Acr proteins predominantly benefit Acr-positive phages only and therefore provide a greater fitness advantage during competition with Acr-negative phages. This work further helps to explain what defines the strength of an Acr protein, how selection acts on different Acr types in a phage community context, and how this can shape the dynamics of phage populations in natural communities.

microbiology↗

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↗