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Koskella, B.

Publications and source records attributed to Koskella, B..

At least 19 recordsLinked to original sources
bioRxiv2026

Enabling the prediction of phage receptor specificity from genome data

Predicting which receptor a phage binds to from genome sequence alone has remained an intractable challenge, principally because the experimental phenotypic data required to train and validate predictive models have not been available at sufficient scale. Here we address this by conducting 1,050 genome-wide genetic screens across 255 taxonomically diverse Escherichia coli dsDNA phages, assigning host receptors to 193 phages across 19 receptor classes. Comparative genomics and AlphaFold3 structural modelling resolved the sequence determinants of specificity to defined receptor-binding protein domains and individual residues. Machine learning models trained on this dataset predicted host receptor identity from phage genome sequence alone without prior annotation of receptor-binding genes, achieving perfect precision and greater than 80% recall on 49 independently validated phages, and yielding predictions for 1,060 of 1,875 E. coli phage genomes in NCBI. Domain swaps redirected receptor specificity as predicted, and a single amino acid substitution proved both necessary and sufficient to switch recognition between two distinct porins. These results demonstrate that systematic phenotyping at scale makes sequence-based prediction of molecular interaction specificity tractable, with direct implications for phage-based medicine, microbiome engineering and the broader challenge of inferring host-pathogen interaction outcomes from sequence.

microbiology↗
bioRxiv2025

Genome editing of phylogenetically distinct bacteria using portable retron-mediated recombineering

Advanced genome editing technologies have enabled rapid and flexible rewriting of the Escherichia coli genome, benefiting fundamental biology and biomanufacturing. Unfortunately, some of the most useful technologies to advance genome editing in E. coli have not yet been ported into other bacterial species. For instance, the addition of bacterial retrons to the genome editing toolbox has increased the efficiency of recombineering in E. coli by enabling sustained, abundant production of ssDNA recombineering donors by reverse transcription that install flexible, precise edits in the prokaryotic chromosome. To extend the utility of this technology beyond E. coli, we surveyed the portability and versatility of retron-mediated recombineering across three different bacterial phyla (Proteobacteria, Bacillota and Actinomycetota) and a total of 15 different species. We found that retron recombineering is functional in all species tested, reaching editing efficiencies above 20% in six of them, above 40% in three of them, and above 90% in two of them. We also tested the extension of the recombitron architecture optimizations and strain backgrounds in a subset of hosts to additionally increase editing rates. The broad recombitron survey carried out in this study forms the basis for widespread use of retron-derived technologies through the whole Bacteria domain.

bioengineering↗
bioRxiv2024

Phages indirectly maintain plant pathogen defense through regulation of the commensal microbiome

Many infectious diseases are associated with altered communities of bacteriophage viruses (phages). As parasites of bacteria, phages can regulate microbiome diversity and composition and may therefore affect disease susceptibility. Yet observational studies alone do not allow us to determine whether altered phage profiles are a contributor to disease risk, a response to infection, or simply an indicator of dysbiosis. To address this question, we used size-selective filtration to separate plant-associated microbial communities from their respective phages, then transplanted them together or separately onto tomato plants that we subsequently challenged with the bacterial pathogen Pseudomonas syringae. Microbial and phage communities together were more disease-protective than either component was alone, an effect that could not be explained by direct effects of phages on either P. syringae or the plant host. Moreover, the protective effect of phages was strongest when microbial and phage communities were isolated from neighboring field locations (allopatric phages), rather than from the same host plant (sympatric phages). This suggests a Goldilocks effect in which moderate rates of phage lysis maintain a microbiome community structure that is most resistant to pathogen invasion. Overall, our results support the idea that phage communities contribute to plant defenses by modulating the microbiome.

microbiology↗
bioRxiv2024

Evidence for the key roles of the Pseudomonas syringae mobilome in shaping biotic interactions

The mobilome, defined as the collection of mobile genetic elements within a bacterial genome, plays a critical role in the adaptation of bacteria to abiotic and biotic drivers. In particular, prophages have been reported to contribute to bacterial resistance to virulent bacteriophages, the competitive interaction of bacterial hosts within microbial communities, and in pathogenicity and virulence. It is therefore critical to better understand the role of prophages in distributing genes and functions within and among bacterial species to predict how bacteria adapt to their biotic environment. Pseudomonas syringae offers an ideal study system to ask these questions both because of its broad range of lifestyles (spanning from environmental growth to plant pathogens) and its high intraspecies diversity. To examine the role of the mobilome in this species complex, we compared 590 genomes available from public databases and annotated the defense mechanisms, effectors, and prophages in the genomes. We found that this species complex has an elaborate phage pandefensome consisting of 139 defense mechanisms. Host-associated P. syringae isolates were found to have both elaborate phage defensomes and effectoromes. Assessing taxonomical signatures of the observed prophages uncovered broad differences in the types and numbers of genes encoded by different phage families, emphasizing how the evolutionary advantages conferred to hosts will depend on the prophage composition and offering insight to how these genes might disperse within a community. Our study highlights the intimate association of phage families with their hosts and uncovers their key role in shaping ecology for this widespread species complex. Significance statementThe bacterial accessory genome, including the mobilome and prophages, plays a critical role in shaping bacterial adaptation to abiotic and biotic drivers. These prophages are widespread across bacterial taxa and likely maintained because of their evolutionary advantage. Our ability to predict how a bacterial population will evolve over time requires a better understanding of where key functional traits arrive. To address this question, we assessed prophage-encoded phage defenses and effector across Pseudomonas syringae. We show that prophages carrying these genes belong to specific phage taxa with differences in the types of genes encoded. This emphasizes the evolutionary advantage of these prophages, offering a framework to uncover how these genes disperse within microbial communities and their role in pathogen evolution.

microbiology↗
bioRxiv2024

Phage as signatures of healthy microbiomes

Parasites are foundational to ecosystem health both as indicator species of community productivity but also as drivers of diversity. In bacterial communities, bacteriophage viruses can play such a role as they track the dynamic composition of bacterial hosts, and in the case of lytic phages, confer a growth advantage to lower abundance bacteria while adapting to more common ones. We set out to test whether viromes can be used as signatures of microbiome health using previously published results across systems. By comparing observed phage and bacterial diversity between microbiomes characterized by disturbance (so-called dysbiosis) and those considered control populations, we were able to identify some key commonalities. While just under half of studies report significant changes in viral species richness in dysbiosis, just under two thirds of studies find the viral composition to shift in dysbiosis, with specific viral taxa enrichment acting as a common signature of dysbiosis. Our analyses also suggest that the positive relationship between bacteriome and virome alpha diversity observed in health breaks down under microbiome disturbance. Overall, while specific viral signatures of dysbiosis are likely to be highly disease- and condition-specific, existing ecological theory shows clear promise in predicting and explaining microbiome health. Future data on bacteria-phage diversity relationships may provide us with much needed opportunity to diagnose, treat, and better understand the causes of dysbiosis. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSBeing able to identify signatures of microbiome health (or lack thereof) has the potential to improve the way we diagnose and treat disease. To do this, the bacterial microbiome is traditionally characterised at the 16S taxonomic level, and changes in composition are linked to changes in disease status. More recently, the field of viromics has gained attention, and studies have begun to probe the relationship between the virome and health or disturbance ( dysbiosis). This work has focused to date on finding single phages that indicate presence of known pathogens, or in a few cases the relationship between viral diversity and disease. To our knowledge, no work has yet sought to identify a common signature of dysbiosis or find commonalities across systems that suggest a role for phages in dysbiosis. Decades of ecological theory has shown how parasites can shape the ecology and evolution of their hosts, and here we argue that bacteriophage viruses have the potential to shape these same processes within microbial communities. The motivation for the current work was thus to ask whether existing ecological theory could help us identify viral signatures of dysbiosis in the microbiome. Added value of this studyThis study employed a systematic review and meta-analysis to test whether and when phage communities can be used as signatures of microbiome health. To do this, we synthesized previously published results that measure composition of the virome between bacterial microbiomes characterised by health or dysbiosis. We found a total of 39 studies across human, mouse, pig and cow hosts that spanned a diverse spectrum of dysbioses, including bacterial infections, viral infections, and varied diseases such as cancer, cirrhosis, and inflammatory bowel disease, and identified a number of commonalities. Just under half of these studies reported a significant change in viral species richness in dysbiosis, and just under two thirds reported the viral composition to shift in dysbiosis. While the vast majority of studies report an enrichment of specific viral taxa associated with dysbiosis, there is little overlap among studies regarding the identity of these enriched taxa. Finally, our analysis provides evidence that the positive relationship between bacteriome and virome alpha diversity breaks down in dysbiosis. Implications of all available evidenceSynthesis of the available evidence suggests that while looking for specific viral taxa as signatures may be limited to associations that are highly disease or condition specific, there is promise for the use of existing ecological theory in predicting and explaining microbiome health when considering compositional changes in the virome. Prospective studies should look to expand the data we have on bacteria-phage relationships at the level of species richness and community compositions, and we argue that more routinely investigating the virome or phageome, in addition to collecting 16S taxonomic descriptions of the microbial community, would help improve our ability to identify signatures of microbiome health. These viral signatures may offer early warning signs of microbiome disturbance and disease. This has clear relevance to our ability to diagnose, treat, and understand the underlying causes of disease.

microbiology↗
bioRxiv2023

Genomic characterization of Pseudomonas syringae pv. syringae from Callery pear and the efficiency of associated phages in disease protection

Pseudomonas syringae is a heterogeneous species complex of plant pathogenic bacteria associated with a wide distribution of plant species. Advances in genomics are revealing the complex evolutionary history of this species complex and the wide array of genetic adaptations underpinning their diverse lifestyles. Here, we genomically characterize two P. syringae isolates collected from diseased Callery pears (Pyrus calleryana) in Berkeley, California in 2019 and 2022. We also isolated a lytic bacteriophage, which we characterized and evaluated for biocontrol efficiency. Using a multilocus sequence analysis and core genome alignment, we classified the P. syringae isolates as members of phylogroup two, related to other strains previously isolated from Pyrus and Prunus. An analysis of effector proteins demonstrated an evolutionary conservation of effectoromes across isolates classified in PG2, and yet uncovered unique effector profiles for each, including the two newly identified isolates. Whole genome sequencing of the associated phage uncovered a novel phage genus related to Psa phage PHB09 and the Flaundravirus genus. Finally, using in planta infection assays, we demonstrate that the phage was equally useful in symptom mitigation of immature pear fruit regardless of the Pss strain tested. Overall, this study demonstrates the diversity of P. syringae and their viruses associated with ornamental pear trees, posing spill-over risks to commercial pear trees and the possibility of using phages as biocontrol agents to reduce the impact of disease.

microbiology↗
bioRxiv2023

Transmission mode shapes host specialization of the phyllosphere microbiome

The collection of microorganisms inhabiting aboveground plant tissue, termed the phyllosphere microbiome, is shaped by both microbial dispersal and host filtering effects. Because plants often occur in multispecies assemblages, microbiome diversity is likely shaped by plant community composition through microbial transmission between conspecific (same species) and heterospecific (different species) host plants. Although rarely examined, the relative incidence of con-versus heterospecific transmission should impact microbiome-level specialization. Using four species of plants we experimentally tested this idea by passaging an initially diverse microbial community either between conspecific or heterospecific plants in the greenhouse. While conspecific transmission lines exhibited persistent host effects, these effects decreased in the heterospecific transmission lines, suggesting a shift towards more generalist microbiomes. Similarly, when microbiomes were transplanted onto a set of novel host plant species, host effects were weaker for these heterospecific lines than the conspecific lines. Finally, microbiomes conspecifically passaged on tomato plants were found to outcompete those passaged on either bean or pepper when co-inoculated onto tomato hosts, suggesting microbiome-level host specialization under conspecific transmission. Overall, we find that both transmission mode and host association history shape microbiome diversity, that repeated conspecific transmission results in microbiome specialization, and that repeated heterospecific transmission can drive microbiomes to develop generalist characteristics.

ecology↗
bioRxiv2022

Within-host adaptation alters priority effects within the phyllosphere microbiome

To predict microbiome composition and function over time, it is essential to understand how evolution alters priority effects between resident and invading species. In an experimental evolution study on tomato plants, an early-colonizing bacterial species rapidly evolved to invade a new niche, altering its ecological interactions with other members of the plant microbiome, as well as its effect on the host. Prevailing models have assumed that adaptation primarily improves the efficiency of resident species within their existing niches, yet we conclude that host habitats can offer alternative evolutionary opportunities, complicating the application of existing theory to the community ecology of microbiomes.

ecology↗
bioRxiv2022

Leaf side determines the relative importance of dispersal versus host filtering in the phyllosphere microbiome

Leaf surface-associated bacterial communities play a significant role in plant health and have therefore been the focus of increasing interest. Despite this, we currently lack a predictive understanding of how leaf-associated bacterial communities are structured within and across hosts, including how leaf traits shape this variation and how community assembly processes may differ across distinct microbial habitats on a leaf. In this study, we characterize the composition of bacterial phyllosphere communities from the upper and lower leaf surfaces of 66 plants across 24 species grown at a common site using 16S rRNA amplicon sequencing. By comparing leaves that vary in pH and stomatal densities and analyzing the leaf surfaces separately, we were able to test the key factors shaping the phyllosphere across host plant species from diverse geographical origins. We found a surprisingly large shared/core microbiome across species, as well as a strong effect of plant species and native origin in shaping composition. Importantly, we found the lower leaf side, where pH values are generally lower and stomatal densities higher, to have lower taxonomic richness relative to the upper leaf side. While the upper leaf side community appears to be more strongly influenced by dispersal effects, the lower leaf appears to be more strongly influenced by plant host filtering effects, as supported by higher relative abundance of shared core taxa and higher signatures of endemism. This work highlights important differences in community assembly processes across the upper and lower leaf microbiomes and underscores the importance of considering differences among habitats within a host when explaining microbial community assembly and composition.

microbiology↗
bioRxiv2022

Early phyllosphere microbial associations impact plant reproductive success

O_LIThe above-ground plant microbiome (the phyllosphere) is increasingly recognized as an important component of plant health. We hypothesized that phyllosphere interactions may be disrupted in a greenhouse setting, where microbial dispersal is limited, and that adding a microbial amendment might yield important benefits to the host plant. C_LIO_LIUsing a newly developed synthetic phyllosphere microbiome for Tomato, we tested this hypothesis across multiple trials by manipulating microbial colonization of leaves and measuring subsequent plant growth and reproductive success, comparing results from plants grown in both greenhouse and field settings. C_LIO_LIWe confirmed that greenhouse-grown plants have a depauperate phyllosphere microbiome and that the addition of the synthetic microbial community was responsible for a clear and repeatable increase in fruit production in this setting. We further show that this effect is synergistic with the addition of micronutrient-based soil amendments, with important implications for agriculture. C_LIO_LIThese results suggest that greenhouse environments have poor phyllosphere microbiome establishment, with negative impacts on the plant. The results also implicate the phyllosphere microbiome as a key component of plant fitness, emphasizing that these communities have a clear role to play in the ecology and evolution of plant communities. C_LI

plant biology↗
bioRxiv2022

Relative abundance data can misrepresent heritability of the microbiome

Host genetics can shape microbiome composition, but to what extent it does, remains unclear. Like any other complex trait, this question can be addressed by estimating the heritability (h2) of the microbiome - the proportion of variance in the abundance of each taxon that is attributable to host genetic variation. However, unlike most complex traits, microbiome heritability is typically based on relative abundance data, where taxon-specific abundances are expressed as the proportion of the total microbial abundance in a sample. We derived an analytical approximation for the heritability that one obtains when using such relative abundances and we uncovered three problems: 1) The interdependency between taxa leads to imprecise heritability estimates. 2) Large sample size leads to high false discovery rates, overestimating the number of heritable taxa. 3) Microbial co-abundances lead to biased heritability estimates. We conclude that caution must be taken when interpreting heritability estimates and comparing values across studies.

evolutionary biology↗
bioRxiv2022

Historical contingency drives compensatory evolution and rare reversal of phage resistance

Bacteria and lytic viruses (phages) engage in highly dynamic coevolutionary interactions over time, yet we have little idea of how transient selection by phages might shape the future evolutionary trajectories of their host populations. To explore this question, we generated genetically diverse phage-resistant mutants of the bacterium Pseudomonas syringae. We subjected the panel of mutants to prolonged experimental evolution in the absence of phages. Some populations re-evolved phage sensitivity, while others acquired compensatory mutations that reduced the costs of resistance without altering resistance levels. To ask whether these outcomes were driven by the initial genetic mechanisms of resistance, we next evolved independent replicates of each mutant lineage in the absence of phages. We found a strong signature of historical contingency: some mutations were highly reversible across replicate populations, while others were highly entrenched. Through whole-genome sequencing of bacteria over time, we also found that populations with resistance mutations in the same gene acquired more parallel sets of mutations than populations with resistance mutations in different genes, suggesting that compensatory adaptation is also contingent on how resistance initially evolved. Our study identifies an evolutionary ratchet in bacteria-phage coevolution, and may explain previous observations that resistance persists over time in some bacterial populations but is lost in others. We add to a growing body of work describing the key role of phages in the ecological and evolutionary dynamics of their host communities. Beyond this specific trait, our study provides new insight into the genetic architecture of historical contingency, a crucial component of interpreting and predicting evolution.

evolutionary biology↗
bioRxiv2021

Induction of autotetraploidy and microbiome associations mediate differential responses to pathogens

It has become increasingly clear that the microbiome plays a critical role in shaping the host organisms response to disease. There also exists mounting evidence that an organisms ploidy level is important in their response to pathogens and parasites. However, no study has determined if or how these two factors influence one another. We investigate the effect of whole-genome duplication in Arabidopsis thaliana on their above-ground (phyllosphere) microbiome, and determine the interacting impacts of ploidy and the microbiome on disease outcome. Using seven independently derived synthetic auto-tetraploid Arabidopsis accessions, a synthetic leaf-associated bacterial community, and the model pathogen Pseudomonas syringae pv. Tomato DC3000, we confirm that polyploids are generally more resistant to pathogens, but illustrate that this resistance may be in part due to a decrease in the reliance on beneficial bacteria. Polyploids fare better against the pathogen than diploids regardless of microbial inoculation, while we observed that diploids harboring an intact microbiome have lower pathogen densities than those without. We then use RNA sequencing to show that diploids have many more differentially expressed defense-related genes in the presence of their phyllosphere microbiota, while polyploids exhibit constitutively activated defenses regardless of exposure to the synthetic community. These results imply that whole-genome duplication can disrupt historical host-microbiome associations, and suggest that a potential cause or consequence of disruption is a heightened capacity for pathogen defense that is less impacted by the microbiome.

plant biology↗
bioRxiv2021

Plant neighborhood shapes diversity and reduces interspecific variation of the phyllosphere microbiome

Microbial communities associated with plant leaf surfaces (i.e. the phyllosphere) are increasingly recognized for their role in plant health. While accumulating evidence suggests a role for host filtering of its microbiota, far less is known about how community composition is shaped by dispersal, including from neighboring plants. We experimentally manipulated the local plant neighborhood within which tomato, pepper, or bean plants were grown in a three-month field trial. Focal plants were grown in the presence of con- or hetero-specific neighbors (or no neighbors) in a fully factorial combination. At 30-day intervals, focal plants were harvested and replaced with a new age- and species-matched cohort while allowing neighborhood plants to continue growing. 16S community profiling revealed that the strength of host filtering effects (i.e. interspecific differences in composition) decreased over time. In contrast, the strength of neighborhood effects increased over time, suggesting dispersal from neighboring plants becomes more important as neighboring plant biomass increases. We next implemented a cross-inoculation study in the greenhouse using inoculum generated from the field plants to directly test host filtering of microbiomes while controlling for directionality and source of dispersal. This experiment further demonstrated that focal host species, the host from which the microbiome came, and in one case the donor hosts neighbors, contribute to variation in phyllosphere bacterial composition. Overall, our results suggest that local dispersal is a key factor in phyllosphere assembly, and that demographic factors such as nearby neighbor identity and biomass or age are important determinants of phyllosphere microbiome diversity.

ecology↗
bioRxiv2021

Water Stress and Disruption of Mycorrhizae Induce Parallel Shifts in Phyllosphere Microbiome Composition

Water and nutrient limitation are key stressors that affect plant health and ecosystem function. These environmental factors impact both soil- and root-associated microbial communities, and systemically alter plant physiology, but it is less clear how they affect aboveground plant-microbe interactions. Through experimental manipulations in the field and growth chamber, we examined the interacting effects of irrigation, soil fertility, and root mycorrhizal associations on bacterial and fungal communities of the tomato phyllosphere (Solanum lycopersicum). Both water stress and mycorrhizal disruption reduced bacterial richness within plants, homogenized bacterial community diversity among plants, and reduced the relative abundance of dominant fungal taxa. We observed striking parallelism in the individual microbial taxa affected by irrigation and mycorrhizal associations. Given the increasingly understood role of the phyllosphere in shaping plant health and pathogen susceptibility, these results offer an additional mechanism by which belowground conditions shape plant fitness.

ecology↗
bioRxiv2020

High-throughput mapping of the phage resistance landscape in E. coli

Bacteriophages (phages) are critical players in the dynamics and function of microbial communities and drive processes as diverse as global biogeochemical cycles and human health. Phages tend to be predators finely tuned to attack specific hosts, even down to the strain level, which in turn defend themselves using an array of mechanisms. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. We also identify both phage specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. Our systematic and high-throughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phage-mediated selection will shape bacterial phenotype and evolution. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering.

microbiology↗
bioRxiv2019

Why evolve reliance on the microbiome for timing of ontogeny?

The timing of life history events has important fitness consequences. Since the 1950s, researchers have combined first principles and data to predict the optimal timing of life history transitions. Recently, a striking mystery has emerged. Such transitions can be shaped by a completely different branch of the tree of life: bacterial species in the microbiome. Probing these interactions using testable predictions from evolutionary theory could illuminate whether and how host-microbiome integrated life histories can evolve and be maintained. Beyond advancing fundamental science, this research program could yield important applications. In an age of microbiome engineering, understanding the contexts that lead to microbiota signaling shaping ontogeny could offer novel mechanisms for manipulations to increase yield in agriculture, or reduce pathogen transmission by affecting vector efficiency. We combine theory and evidence to illuminate the essential questions underlying the existence of Microbiome Dependent Ontogenetic Timing (MiDOT) to fuel research on this emerging topic.

evolutionary biology↗
bioRxiv2019

Protective microbiomes can limit the evolution of host pathogen defense

The evolution of host immunity occurs in the context of the microbiome, but little theory exists to predict how resistance against pathogens might be influenced by the need to tolerate and regulate commensal microbiota. We present a general model to explore the optimal investment in host immunity under conditions in which the host can, versus cannot easily distinguish among commensal versus pathogenic bacteria; and when commensal microbiota can, versus cannot protect the host against the impacts of pathogen infection. We find that a loss of immune vigilance associated with innate immunity over evolutionary time can occur due to the challenge of discriminating between pathogenic and other microbe species. Further, we find the greater the protective effect of microbiome species, acting either directly or via competition with a pathogen, or the higher the costs of immunity, the more likely the loss of immune vigilance is. Conversely, this effect can be reversed when pathogens increase host mortality. Generally, the magnitude of costs of immunity required to allow evolution of decreased immune vigilance are predicted to be lowest when microbiome and pathogen species most resemble each other (in terms of host recognition), and when immune effects on the pathogen are weak. Our model framework makes explicit the core trade-offs likely to shape the evolution of immunity in the context of microbiome / pathogen discrimination. We discuss how this informs interpretation of patterns and process in natural systems, including vulnerability to pathogen emergence.\n\nImpact SummaryEvidence for impacts of the microbiome on host health is accumulating. Despite this, little theory has been developed to delineate the evolutionary trajectories that might lead to observed host-microbiome associations. One particularly important theoretical gap is evaluating how the presence and effects of microbiome species modify selection pressure on immune system function. We develop a simple model of host fitness given both immune discrimination and microbiome and pathogen effects on survival, in the context of an interaction between the microbiome and pathogen species. We use this framework to predict when and to what degree the presence of microbiome species might lead to loss of immune vigilance. Positive microbiome effects can drive loss of immune vigilance, whether the microbiome acts directly on pathogen growth or indirectly by reducing the impacts of pathogens; and high costs of immunity will amplify this effect. Our results provide a first set of predictions regarding how immunity should evolve given the challenge of discriminating pathogen and microbiome species, and reveals the ways in which this might leave hosts vulnerable to novel pathogens.

evolutionary biology↗