Drivers and consequences of coevolution in protective symbiosis

Project Information

COEVOPRO

Grant agreement ID: 802242

DOI

10.3030/802242

Project closed

EC signature date 14 August 2018

Start date 1 February 2019

End date 31 January 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 275,00

EU contribution

€ 1 499 275,00

Coordinated by

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

Periodic Reporting for period 4 - COEVOPRO (Drivers and consequences of coevolution in protective symbiosis)

Reporting period: 2023-08-01 to 2025-01-31

Summary of the context and overall objectives of the project

All organisms in nature are targets for parasite attack. Symbiotic microbial species living within hosts can provide a strong barrier against infection, beyond the host’s own immune response. We now know that ‘protective microbes’ are key components of plant, animal, and human microbiota, determining host health in the face of pathogen infection. The realisation that these microbes can evolve challenges our understanding of how hosts may resist infections diseases across evolutionary time. We have used an approach called 'experimental evolution', followed by detailed genomic analysis, to understand the evolutionary and ecological dynamics of these defensive symbiotic interactions. Among other findings, we have shown: 1) the microbiota can facilitate infection and indeed worsen disease severity, as well as accelerate pathogen evolution thereby advancing our thinking on microbiota-pathogen relationships, 2) microbial protection during coevolution resulted in the evolution of host tolerance and in parasites adapting to microbial defenses, 3) parasite heterogeneity in the environment does not diminish the evolvability of protective microbes, and 4) the physiological/resource costs of protective microbes suggest there is strong selection on hosts to regulate microbe densities. Overall, we have also discovered new ways in which microbes can evolve along the mutualist-parasite continuum to protect or harm their host. COEVOPRO has pushed the conceptual boundaries for thinking about 'protective microbes' in environmental and clinical settings.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

WP1: To test the ability of microbes to evolve more rapidly than host-encoded resistance against parasites
Defensive microbial symbionts provide hosts with evolvable protection against pathogens. In these networks, hosts and defensive symbionts can encounter a diversity of eco-evolutionary contexts imposed by pathogens. When under attack from coevolving pathogens, will hosts rely on symbionts or in their own defence mechanisms? In turn, how will coevolving pathogens shape the evolutionary trajectories of defensive symbiont populations? After evolving worm hosts (Caenorhabditis elegans) and and their good/bad microbes altogether, we found evidence of host dependence and pathogen virulence emerging under network evolution. The study provides the first insight into how eco-evolutionary complexity shapes fitness and diversity in a community of hosts, defensive symbionts & pathogens. This research is currently still in the publication pipeline. A related computational meta-analysis across the tree of symbiotic life has shown that the degree of both protection and cost scales positively with symbiont density, suggesting there is selection for hosts to regulate symbiont densities (published in American Naturalist in 2022).
WP2: To uncover the impacts of evolving protective microbes on host-parasite coevolution
We conducted an evolution experiment involving co-passaged populations of nematode hosts and pathogens when hosts were colonized (or not) by defensive bacteria. As published in Current Biology in 2022, we found that microbial protection during coevolution drove patterns of host tolerance and in parasites adapting to microbial defenses. At the genomic level, we found parasite populations had diverged between protected and unprotected hosts.
WP3: To test whether and how parasite heterogeneity affects host-protective microbe coevolution
We experimentally coevolved populations of worm hosts with protective bacteria in treatments varying the infection frequency with pathogens. In a study published in Ecology and Evolution in 2020, we found that when nfection varied every host generation, alternating host generations, every fifth host generation, or never. Our results showed that enhanced microbe-mediated protection evolved under all conditions when the pathogen was present, even rarely. Our results suggest that resident microbes can be a form of transgenerational immunity against rare pathogen infection.
WP4: To test whether and how host microbiota shapes host-protective microbe coevolution
Pathogens newly invading a host must compete with resident microbiota. Within-host microbial warfare could lead to more severe disease outcomes or constrain the evolution of virulence. In a study published in ISME J in 2025, we experimentally evolved pathogens and a native microbiota community in worm hosts to show that a competitively superior pathogen displaced microbiota and reduced species richness. However, its virulence was maintained across generations. Whole genome sequencing revealed shifts in the mode of selection with competitive interactions driving early diversification among pathogen populations. This work reveals how microbial competition during emerging infection determines the patterns and processes of evolution with major consequences for host health. As an extension of this research, we conducted transcriptomic analyses of worms colonised by its native microbiota and pathogens (pub in Molecular Ecology in 2025) exploring the impact of 're-wilding' a model animal with native microbiome on immunological patterns.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

All of these achievements thus far have been unplanned/unexpected as they sprung from discussions/thinking that occurred during the lab lockdowns during the pandemic's first wave. Given the focus of the field on examining the protective impact of host microbiota against pathogen infection, our pursuit to understand the ability of microbiota and its components to facilitate or promote infection advances our thinking on microbiota-disease relationships, particularly in the context of health. We have written a review (Stevens et al 2021 PLoS Pathogens) which discusses the mechanisms underlying the facilitation as well as the evolutionary implications. Moreover, another review (Drew et al. 2021 Nature Review Microbiology) we have written has highlighted the diversity of ways in which microbes can evolve along the mutualist-parasite continuum, contributing to our understanding of the evolutionary and ecological dynamics in symbiotic relationships.

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