Invasive species modulate the structure and stability of a multilayer mutualistic network.

Species interactions are critical for maintaining community structure and dynamics, but the effects of invasive species on multitrophic networks remain poorly understood. We leveraged an ongoing invasion scenario in Patagonia, Argentina, to explore how non-native ungulates affect multitrophic networks. Ungulates disrupt a hummingbird-mistletoe-marsupial keystone interaction, which alters community composition. We sampled pollination and seed dispersal interactions in intact and invaded sites. We constructed pollination and seed dispersal networks for each site, which we connected via shared plants. We calculated pollination-seed dispersal connectivity, identified clusters of highly connected species, and quantified species' roles in connecting species clusters. To link structural variation to stability, we quantified network tolerance to single random species removal (disturbance propagation) and sequential species removal (robustness) using a stochastic coextinction model. Ungulates reduced the connectivity between pollination and seed dispersal and produced fewer clusters with a skewed size distribution. Moreover, species shifted their structural role, fragmenting the network by reducing the 'bridges' among species clusters. These structural changes altered the dynamics of cascading effects, increasing disturbance propagation and reducing network robustness. Our results highlight invasive species' role in altering community structure and subsequent stability in multitrophic communities.

Competition for hosts modulates vast antigenic diversity to generate persistent strain structure in Plasmodium falciparum.

In their competition for hosts, parasites with antigens that are novel to the host immune system will be at a competitive advantage. The resulting frequency-dependent selection can structure parasite populations into strains of limited genetic overlap. For the causative agent of malaria, Plasmodium falciparum, the high recombination rates and associated vast diversity of its highly antigenic and multicopy var genes preclude such clear clustering in endemic regions. This undermines the definition of strains as specific, temporally persisting gene variant combinations. We use temporal multilayer networks to analyze the genetic similarity of parasites in both simulated data and in an extensively and longitudinally sampled population in Ghana. When viewed over time, populations are structured into modules (i.e., groups) of parasite genomes whose var gene combinations are more similar within than between the modules and whose persistence is much longer than that of the individual genomes that compose them. Comparison to neutral models that retain parasite population dynamics but lack competition reveals that the selection imposed by host immunity promotes the persistence of these modules. The modular structure is, in turn, associated with a slower acquisition of immunity by individual hosts. Modules thus represent dynamically generated niches in host immune space, which can be interpreted as strains. Negative frequency-dependent selection therefore shapes the organization of the var diversity into parasite genomes, leaving a persistence signature over ecological time scales. Multilayer networks extend the scope of phylodynamics analyses by allowing quantification of temporal genetic structure in organisms that generate variation via recombination or other non-bifurcating processes. A strain structure similar to the one described here should apply to other pathogens with large antigenic spaces that evolve via recombination. For malaria, the temporal modular structure should enable the formulation of tractable epidemiological models that account for parasite antigenic diversity and its influence on intervention outcomes.

The interplay between vaccination and social distancing strategies affects COVID19 population-level outcomes.

Social distancing is an effective population-level mitigation strategy to prevent COVID19 propagation but it does not reduce the number of susceptible individuals and bears severe social consequences-a dire situation that can be overcome with the recently developed vaccines. Although a combination of these interventions should provide greater benefits than their isolated deployment, a mechanistic understanding of the interplay between them is missing. To tackle this challenge we developed an age-structured deterministic model in which vaccines are deployed during the pandemic to individuals who do not show symptoms. The model allows for flexible and dynamic prioritization strategies with shifts between target groups. We find a strong interaction between social distancing and vaccination in their effect on the proportion of hospitalizations. In particular, prioritizing vaccines to elderly (60+) before adults (20-59) is more effective when social distancing is applied to adults or uniformly. In addition, the temporal reproductive number Rt is only affected by vaccines when deployed at sufficiently high rates and in tandem with social distancing. Finally, the same reduction in hospitalization can be achieved via different combination of strategies, giving decision makers flexibility in choosing public health policies. Our study provides insights into the factors that affect vaccination success and provides methodology to test different intervention strategies in a way that will align with ethical guidelines.

Asymmetric disease dynamics in multihost interconnected networks.

Epidemic spread in single-host systems strongly depends on the population's transmission network. However, little is known regarding the spread of epidemics across networks representing populations of multiple hosts. We explored cross-species transmission in a multilayer network where layers represent populations of two distinct hosts, and disease can spread across intralayer (within-host) and interlayer (between-host) edges. We developed an analytic framework for the SIR epidemic model to examine the effect of (i) source of infection and (ii) between-host asymmetry in infection probabilities, on disease risk. We measured risk as outbreak probability and outbreak size in a focal host, represented by one network layer. Numeric simulations were used to validate the analytic formulations. We found that outbreak probability is determined by a complex interaction between source of infection and between-host infection probabilities, whereas outbreak size is mainly affected by the non-focal host to focal host infection probability. Hence, inter-specific asymmetry in infection probabilities shapes disease dynamics in multihost networks. These results highlight the importance of considering multiple measures of disease risk and advance our understanding of disease spread in multihost systems. The study provides a flexible way to model disease dynamics in multiple hosts while considering contact heterogeneity within and between species. We strongly encourage empirical studies that include information on both cross-species infection rates and network structure of multiple hosts. Such studies are necessary to corroborate our theoretical results and to improve our understanding of multihost epidemiology.

The effect of water contamination and host-related factors on ectoparasite load in an insectivorous bat.

We examined the effects of sex, age, and reproductive state of the insectivorous bat Pipistrellus kuhlii on the abundance and prevalence of arthropod ectoparasites (Macronyssidae and Cimicidae) in habitats with either sewage-polluted or natural bodies of water, in the Negev Desert, Israel. We chose water pollution as an environmental factor because of the importance of water availability in desert environments, particularly for P. kuhlii, which needs to drink on a daily basis. We predicted that parasite infestation rates would be affected by both environment and demographic cohort of the host. We found that female bats in the polluted site harbored significantly more mites than female bats in the natural site and that juveniles in the polluted site harbored significantly more cimicid individuals than juveniles in the natural site. We further found that age and sex (host-related factors) affected ectoparasite prevalence and intensity (i.e., the abundance of parasites) in the polluted site. Our results may suggest that the interaction between host-related and environment-related factors affected parasite infestations, with females and young bats being more susceptible to ectoparasites when foraging over polluted water. This effect may be particularly important for bats that must drink or forage above water for other wildlife that depend on drinking water for survival.

Habitat fragmentation alters the properties of a host-parasite network: rodents and their helminths in South-East Asia.

1. While the effects of deforestation and habitat fragmentation on parasite prevalence or richness are well investigated, host-parasite networks are still understudied despite their importance in understanding the mechanisms of these major disturbances. Because fragmentation may negatively impact species occupancy, abundance and co-occurrence, we predict a link between spatiotemporal changes in habitat and the architecture of host-parasite networks. 2. For this, we used an extensive data set on 16 rodent species and 29 helminth species from seven localities of South-East Asia. We analysed the effects of rapid deforestation on connectance and modularity of helminth-parasite networks. We estimated both the degree of fragmentation and the rate of deforestation through the development of land uses and their changes through the last 20 to 30 years in order to take into account the dynamics of habitat fragmentation in our statistical analyses. 3. We found that rapid fragmentation does not affect helminth species richness per se but impacts host-parasite interactions as the rodent-helminth network becomes less connected and more modular. 4. Our results suggest that parasite sharing among host species may become more difficult to maintain with the increase of habitat disturbance.

Multiple effects of host-species diversity on coexisting host-specific and host-opportunistic microbes.

While host-species diversity often influences microbial prevalence, there may be multiple mechanisms causing such effects that may also depend on the foraging strategy of the microbes. We employed a natural gradient of rodent-species richness to examine competing hypotheses describing possible mechanisms mediating the relationship between host-species richness and the prevalence of the most dominant microbes, along with microbe specificity to the different rodent host species. We sampled blood from three gerbil species in plots differing in terms of the proportion of the different species and screened for the most dominant bacteria. Two dominant bacterial lineages were detected: host-specific bacteria and host-opportunistic bacteria. Using a model selection approach, we detected evidence for both direct and indirect effects of host-species richness on the prevalence of these bacteria. Infection probability of the host-specific lineage was lower in richer host communities, most likely due to increased frequency and density of the least suitable host species. In contrast, field observations suggest that the effect of host-species richness on infection probability of the opportunistic lineage was both direct and indirect, mostly mediated by changes in flea densities on the host and by the presence of the host-specific lineage. Our results thus suggest that host-species richness has multiple effects on microbial prevalence, depending on the degree of host-specificity of the microbe in question.

A trade-off between quantity and quality of offspring in haematophagous ectoparasites: the effect of the level of specialization.

Theory predicts an adaptive trade-off between quantity and quality of offspring if mothers can reliably predict the offspring environment. We studied egg production and quality of offspring in two flea species (host-specialist Parapulex chephrenis and host-generalist Xenopsylla ramesis) exploiting eight rodent species. We evaluated quality of new imagoes via their developmental time, size (length of a femur as a proxy) and resistance to starvation without a blood meal. We predicted that the offspring quality would increase with (i) a decrease in the number of eggs produced by mothers and (ii) an increase in phylogenetic distance between maternal host and principal host of a flea. We also predicted that negative relationships between offspring quality and either maternal egg production effort or phylogenetic distance between maternal host and the principal host or both would be manifested stronger in host-opportunistic than in host-specific fleas. The highest number of eggs produced per female flea was accompanied by the longest duration of development and the smallest offspring in X. ramesis, while P. chephrenis that hatched from larger clutches survived for less time under starvation. Although there was no significant effect of host species on any dependent variable, association between offspring quality and phylogenetic distance of the maternal host from the principal host of a flea was found in X. ramesis (but not P. chephrenis) with new imagoes being larger if their maternal hosts were phylogenetically distant from the principal host. Our results demonstrated stronger trade-off between quantity and quality of offspring in a generalist than in a specialist flea, supporting the association between life-history plasticity and generalist feeding strategy.

Phylogenetic structure of host spectra in Palaearctic fleas: stability versus spatial variation in widespread, generalist species.

We investigated spatial variation in the phylogenetic structure of host spectra in fleas parasitic on small mammals. Measures of phylogenetic host specificity ((phylogenetic species clustering (PSC) and phylogenetic species variability (PSV)) varied significantly more between than within flea species, but the proportion of variation which accounted for among-species differences was low. In 13 of 18 common flea species, at least one of the indices of the phylogenetic structure of regional host spectra revealed a significantly positive association with the phylogenetic structure of regional host assemblage, while relationships between PSC or PSV of the regional host spectrum and the distance from either the region of a flea's maximal abundance or latitude were not supported. Overall, results of this study demonstrated that although the degree of phylogenetic host specificity in fleas can be considered as a true attribute of a flea species, it is highly spatially variable, with phylogenetic structure of the surrounding host pool being the main reason behind this variation.

Plasmids in the human gut reveal neutral dispersal and recombination that is overpowered by inflammatory diseases.

Plasmids are pivotal in driving bacterial evolution through horizontal gene transfer. Here, we investigated 3467 human gut microbiome samples across continents and disease states, analyzing 11,086 plasmids. Our analyses reveal that plasmid dispersal is predominantly stochastic, indicating neutral processes as the primary driver of their wide distribution. We find that only 20-25% of plasmid DNA is being selected in various disease states, constraining its distribution across hosts. Selective pressures shape specific plasmid segments with distinct ecological functions, influenced by plasmid mobilization lifestyle, antibiotic usage, and inflammatory gut diseases. Notably, these elements are more commonly shared within groups of individuals with similar health conditions, such as Inflammatory Bowel Disease (IBD), regardless of geographic location across continents. These segments contain essential genes such as iron transport mechanisms- a distinctive gut signature of IBD that impacts the severity of inflammation. Our findings shed light on mechanisms driving plasmid dispersal and selection in the human gut, highlighting their role as carriers of vital gene pools impacting bacterial hosts and ecosystem dynamics.

Phylogeny determines the role of helminth parasites in intertidal food webs.

1. Parasites affect interactions among species in food webs and should be considered in any analysis of the structure, dynamics or resilience of trophic networks. 2. However, the roles of individual parasite species, such as their importance as connectors within the network, and what factors determine these roles, are yet to be investigated. Here, we test the hypotheses that the species roles of trematode, cestode and nematode parasites in aquatic food webs are influenced by the type of definitive host they use, and also determined by their phylogenetic affiliations. 3. We quantified the network role of 189 helminth species from six highly resolved intertidal food webs. We focused on four measures of centrality (node degree, closeness centrality, betweenness centrality and eigenvalue centrality), which characterize each parasite's position within the web, and on relative connectedness of a parasite species to taxa in its own module vs. other modules of the web (within-module degree and participation coefficient). 4. All six food webs displayed a significant modular structure, that is, they consisted of subsets of species interacting mostly with each other and less with species from other subsets. We demonstrated that the parasites themselves are not generating this modularity, though they contribute to intermodule connectivity. 5. Mixed-effects models revealed only a modest influence of the type of definitive host used (bird or fish) and of the web of origin on the different measures of parasite species roles. In contrast, the taxonomic affiliations of the parasites, included in the models as nested random factors, accounted for 37-93% of the total variance, depending on the measure of species role. 6. Our findings indicate that parasites are important intermodule connectors and thus contribute to web cohesion. We also uncover a very strong phylogenetic signal in parasite species roles, suggesting that the role of any parasite species in a food web, including new invasive species, is to some extent predictable based solely on its taxonomic affiliations.

Temporal dynamics of direct reciprocal and indirect effects in a host-parasite network.

1. Temporal variation in the direct and indirect influence that hosts and parasites exert on each other is still poorly understood. However, variation in species' influence due to species and interactions turnover can have important consequences for host community dynamics and/or for parasite transmission dynamics, and eventually for the risk of zoonotic diseases. 2. We used data on a network of small mammals and their ectoparasites surveyed over 6 years to test hypotheses exploring (i) the temporal variability in direct and indirect influences species exert on each other in a community, and (ii) the differences in temporal variability of direct/indirect influences between temporally persistent (TP) and temporally intermittent species. 3. We modelled the temporal variation in (i) direct reciprocal influence between hosts and parasites (hosts providing resources to parasites and parasites exploiting the resources of hosts), using an asymmetry index, and (ii) indirect influence among species within a community (e.g. facilitation of parasite infestation by other parasites), using betweenness centrality. We also correlated asymmetry and centrality to examine the relationship between them. 4. Network dynamics was determined by TP species but even those species had strong among-species heterogeneity in the temporal variation of the direct/indirect effects they exerted. In addition, there was a significant positive linear correlation between asymmetry and centrality. 5. We conclude that the temporal dynamics of host-parasite interactions is driven by TP hosts. However, even within this group of persistent species, some exhibit large temporal variation, such that the functional roles they play (e.g. in promoting parasite transmission) change over time. In addition, parasites having a large negative impact on hosts are also those facilitating the spread of other parasites through the entire host community. Our results provide new insights into community dynamics and can be applied in the management of antagonistic networks aimed at preventing disease outbreaks.

Conceptualizing microbe-plasmid communities as complex adaptive systems.

Plasmids shape microbial communities' diversity, structure, and function. Nevertheless, we lack a mechanistic understanding of how community structure and dynamics emerge from local microbe-plasmid interactions and coevolution. Addressing this gap is challenging because multiple processes operate simultaneously at multiple levels of organization. For example, immunity operates between a plasmid and a cell, but incompatibility mechanisms regulate coexistence between plasmids. Conceptualizing microbe-plasmid communities as complex adaptive systems is a promising approach to overcoming these challenges. I illustrate how agent-based evolutionary modeling, extended by network analysis, can be used to quantify the relative importance of local processes governing community dynamics. These theoretical developments can advance our understanding of plasmid ecology and evolution, especially when combined with empirical data.

Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness.

Cancer cells alter the expression levels of metabolic enzymes to fuel proliferation. The mitochondrion is a central hub of metabolic reprogramming, where chaperones service hundreds of clients, forming chaperone-client interaction networks. How network structure affects its robustness to chaperone targeting is key to developing cancer-specific drug therapy. However, few studies have assessed how structure and robustness vary across different cancer tissues. Here, using ecological network analysis, we reveal a non-random, hierarchical pattern whereby the cancer type modulates the chaperones' ability to realize their potential client interactions. Despite the low similarity between the chaperone-client interaction networks, we highly accurately predict links in one cancer type based on another. Moreover, we identify groups of chaperones that interact with similar clients. Simulations of network robustness show that this group structure affects cancer-specific response to chaperone removal. Our results open the door for new hypotheses regarding the ecology and evolution of chaperone-client interaction networks and can inform cancer-specific drug development strategies.

Multilayer networks of plasmid genetic similarity reveal potential pathways of gene transmission.

Antimicrobial resistance (AMR) is a significant threat to public health. Plasmids are principal vectors of AMR genes, significantly contributing to their spread and mobility across hosts. Nevertheless, little is known about the dynamics of plasmid genetic exchange across animal hosts. Here, we use theory and methodology from network and disease ecology to investigate the potential of gene transmission between plasmids using a data set of 21 plasmidomes from a single dairy cow population. We constructed a multilayer network based on pairwise plasmid genetic similarity. Genetic similarity is a signature of past genetic exchange that can aid in identifying potential routes and mechanisms of gene transmission within and between cows. Links between cows dominated the transmission network, and plasmids containing mobility genes were more connected. Modularity analysis revealed a network cluster where all plasmids contained a mobM gene, and one where all plasmids contained a beta-lactamase gene. Cows that contain both clusters also share transmission pathways with many other cows, making them candidates for super-spreading. In support, we found signatures of gene super-spreading in which a few plasmids and cows are responsible for most gene exchange. An agent-based transmission model showed that a new gene invading the cow population will likely reach all cows. Finally, we showed that edge weights contain a non-random signature for the mechanisms of gene transmission, allowing us to differentiate between dispersal and genetic exchange. These results provide insights into how genes, including those providing AMR, spread across animal hosts.

Host body microcosm and ectoparasite infracommunities: arthropod ectoparasites are not spatially segregated.

We studied the distribution of ectoparasite species (an ixodid tick, a chigger mite, 7 mesostigmate mites, 5 fleas and 3 lice) on bodies of 5 species of rodent hosts from the marshlands in Argentina to establish whether arthropod ectoparasites are segregated across body parts of the same host individual. We asked (a) whether an individual ectoparasite species prefers certain parts of the body of its host and, if yes, whether these preferences overlap among ectoparasite species; (b) whether ectoparasite species composition differs among different parts of a host's body; and (c) whether co-occurrences of ectoparasite species within pre-defined body parts of a host are non-random and, if yes, whether ectoparasites co-occur in the same body part of a host either less or more often than expected by chance. It was found that, in general, ectoparasite species were not segregated across body parts of a host. Although some ectoparasites preferred certain body parts, these preferences were similar among ectoparasites belonging to different species and/or higher taxa resulting in similarity among host body parts in ectoparasite species composition. In addition, ectoparasite species demonstrated a tendency to co-occur on the same body parts of a host and not to be segregated among them. It was concluded that the distribution of ectoparasites on the body of a small mammalian host is driven mainly by their interaction with the host rather than by distinct preferences or interactions among ectoparasite species.

Habitat aridity as a determinant of the trade-off between water conservation and evaporative heat loss in bats.

The maintenance of water balance in arid environments might represent a formidable challenge for Chiroptera, since they have high surface-to-volume ratios. In deserts, bats conserve water, for example, using daily torpor, but they also might experience episodic heat bouts, when they may need to increase total evaporative water loss (TEWL) to thermoregulate. We hypothesized that in bats, habitat aridity and its variability determine a trade-off between water conservation and thermoregulation via evaporative means. To test this hypothesis, we collated data from the literature of 22 species of bats on TEWL, body temperature and resting metabolic rate, in torpor and euthermy. We also collected data on ambient temperature (Ta) and precipitation of the locations where bats were captured, calculated an aridity index, and built an index of variability of the environment. After correcting for phylogeny, we found that, as aridity and variability of the environment increased, bats had lower values of TEWL, but the rate at which TEWL increases with Ta was higher, supporting our hypothesis. These results suggest that at high Ta there is a trade-off between water conservation and evaporative heat loss in bats. The evolution of physiological mechanisms that allow water conservation and tolerance to conditions of high Ta without access to free water might thus be crucial to explain the distribution of desert bats.

Age-specific patterns of DBLα var diversity can explain why residents of high malaria transmission areas remain susceptible to Plasmodium falciparum blood stage infection throughout life.

Immunity to Plasmodium falciparum is non-sterilising, thus individuals residing in malaria-endemic areas are at risk of infection throughout their lifetime. Here we seek to find a genomic epidemiological explanation for why residents of all ages harbour blood stage infections despite lifelong exposure to P. falciparum in areas of high transmission. We do this by exploring, for the first known time, the age-specific patterns of diversity of variant antigen encoding (var) genes in the reservoir of infection. Microscopic and submicroscopic P. falciparum infections were analysed at the end of the wet and dry seasons in 2012-2013 for a cohort of 1541 residents aged from 1 to 91 years in an area characterised by high seasonal malaria transmission in Ghana. By sequencing the near ubiquitous Duffy-binding-like alpha domain (DBLα) that encodes immunogenic domains, we defined var gene diversity in an estimated 1096 genomes detected in sequential wet and dry season sampling of this cohort. Unprecedented var (DBLα) diversity was observed in all ages with 42,399 unique var types detected. There was a high degree of maintenance of types between seasons (>40% seen more than once), with many of the same types, especially upsA, appearing multiple times in isolates from different individuals. Children and adolescents were found to be significant reservoirs of var DBLα diversity compared with adults. Var repertoires within individuals were highly variable, with children having more related var repertoires compared to adolescents and adults. Individuals of all ages harboured multiple genomes with var repertoires unrelated to those infecting other hosts. High turnover of parasites with diverse isolate var repertoires was also observed in all ages. These age-specific patterns are best explained by variant-specific immune selection. The observed level of var diversity for the population was then used to simulate the development of variant-specific immunity to the diverse var types under conservative assumptions. Simulations showed that the extent of observed var diversity with limited repertoire relatedness was sufficient to explain why adolescents and adults in this community remain susceptible to blood stage infection, even with multiple genomes.

Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission.

In high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires, or strains, in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the response of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more persistent under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the described enhanced persistence under perturbation, intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence.

The network structure and eco-evolutionary dynamics of CRISPR-induced immune diversification.

As a heritable sequence-specific adaptive immune system, CRISPR-Cas is a powerful force shaping strain diversity in host-virus systems. While the diversity of CRISPR alleles has been explored, the associated structure and dynamics of host-virus interactions have not. We explore the role of CRISPR in mediating the interplay between host-virus interaction structure and eco-evolutionary dynamics in a computational model and compare the results with three empirical datasets from natural systems. We show that the structure of the networks describing who infects whom and the degree to which strains are immune, are respectively modular (containing groups of hosts and viruses that interact strongly) and weighted-nested (specialist hosts are more susceptible to subsets of viruses that in turn also infect the more generalist hosts with many spacers matching many viruses). The dynamic interplay between these networks influences transitions between dynamical regimes of virus diversification and host control. The three empirical systems exhibit weighted-nested immunity networks, a pattern our theory shows is indicative of hosts able to suppress virus diversification. Previously missing from studies of microbial host-pathogen systems, the immunity network plays a key role in the coevolutionary dynamics.