Host sexual dimorphism affects the outcome of within‐host pathogen competition

Natural infections often consist of multiple pathogens of the same or different species. When coinfections occur, pathogens compete for access to host resources and fitness is determined by how well a pathogen can reproduce compared to its competitors. Yet not all hosts provide the same resource pool. Males and females, in particular, commonly vary in both their acquisition of resources and investment in immunity, but their ability to modify any competition between different pathogens remains unknown. Using the Daphnia magna–Pasteuria ramosa model system, we exposed male and female hosts to either a single genotype infection or coinfections consisting of two pathogen genotypes of varying levels of virulence. We found that coinfections within females favored the transmission of the more virulent pathogen genotype, whereas coinfections within male hosts resulted in equal transmission of competing pathogen genotypes. This contrast became less pronounced when the least virulent pathogen was able to establish an infection first, suggesting that the influence of host sex is shaped by priority effects. We suggest that sex is a form of host heterogeneity that may influence the evolution of virulence within coinfection contexts and that one sex may be a reservoir for pathogen genetic diversity in nature.     

PATHOGEN LIFE‐HISTORY TRADE‐OFFS REVEALED IN ALLOPATRY

Trade‐offs in life‐history traits is a central tenet in evolutionary biology, yet their ubiquity and relevance to realized fitness in natural populations remains questioned. Trade‐offs in pathogens are of particular interest because they may constrain the evolution and epidemiology of diseases. Here, we studied life‐history traits determining transmission in the obligate fungal pathogen, Podosphaera plantaginis, infecting Plantago lanceolata. We find that although traits are positively associated on sympatric host genotypes, on allopatric host genotypes relationships between infectivity and subsequent transmission traits change shape, becoming even negative. The epidemiological prediction of this change in life‐history relationships in allopatry is lower disease prevalence in newly established pathogen populations. An analysis of the natural pathogen metapopulation confirms that disease prevalence is lower in newly established pathogen populations and they are more prone to go extinct during winter than older pathogen populations. Hence, life‐history trade‐offs mediated by pathogen local adaptation may influence epidemiological dynamics at both population and metapopulation levels.     

Effects of pathogen exposure on life‐history variation in the gypsy moth (Lymantria dispar)

Investment in host defences against pathogens may lead to trade‐offs with host fecundity. When such trade‐offs arise from genetic correlations, rates of phenotypic change by natural selection may be affected. However, genetic correlations between host survival and fecundity are rarely quantified. To understand trade‐offs between immune responses to baculovirus exposure and fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations between survival probability and traits related to fecundity, such as pupal weight. In addition, we tested whether different virus isolates have different effects on male and female pupal weight. To estimate genetic correlations, we exposed individuals of known relatedness to a single baculovirus isolate. To then evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy moth strain to 16 baculovirus isolates. We found a negative genetic correlation between survival and pupal weight. In addition, virus exposure caused late‐pupating females to be identical in weight to males, whereas unexposed females were 2–3 times as large as unexposed males. Finally, we found that female pupal weight is a quadratic function of host mortality across virus isolates, which is likely due to trade‐offs and compensatory growth processes acting at high and low mortality levels, respectively. Overall, our results suggest that fecundity costs may strongly affect the response to selection for disease resistance. In nature, baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens often do in forest‐defoliating insects. We therefore argue that trade‐offs between host life‐history traits may help explain outbreak dynamics.     

Effects of host heterogeneity on pathogen diversity and evolution

Phenotypic variation is common in most pathogens, yet the mechanisms that maintain this diversity are still poorly understood. We asked whether continuous host variation in susceptibility helps maintain phenotypic variation, using experiments conducted with a baculovirus that infects gypsy moth (Lymantria dispar) larvae. We found that an empirically observed tradeoff between mean transmission rate and variation in transmission, which results from host heterogeneity, promotes long‐term coexistence of two pathogen types in simulations of a population model. This tradeoff introduces an alternative strategy for the pathogen: a low‐transmission, low‐variability type can coexist with the high‐transmission type favoured by classical non‐heterogeneity models. In addition, this tradeoff can help explain the extensive phenotypic variation we observed in field‐collected pathogen isolates, in traits affecting virus fitness including transmission and environmental persistence. Similar heterogeneity tradeoffs might be a general mechanism promoting phenotypic variation in any pathogen for which hosts vary continuously in susceptibility.     

Evolution of host resistance and trade‐offs between virulence and transmission potential in an obligately killing parasite

Standard epidemiological theory predicts that parasites, which continuously release propagules during infection, face a trade‐off between virulence and transmission. However, little is known how host resistance and parasite virulence change during coevolution with obligate killers. To address this question we have set up a coevolution experiment evolving Nosema whitei on eight distinct lines of Tribolium castaneum. After 11 generations we conducted a time‐shift experiment infecting both the coevolved and the replicate control host lines with the original parasite source, and coevolved parasites from generation 8 and 11. We found higher survival in the coevolved host lines than in the matching control lines. In the parasite populations, virulence measured as host mortality decreased during coevolution, while sporeload stayed constant. Both patterns are compatible with adaptive evolution by selection for resistance in the host and by trade‐offs between virulence and transmission potential in the parasite.     

Virulence‐driven trade‐offs in disease transmission: A meta‐analysis*

The virulence–transmission trade‐off hypothesis proposed more than 30 years ago is the cornerstone in the study of host–parasite co‐evolution. This hypothesis rests on the premise that virulence is an unavoidable and increasing cost because the parasite uses host resources to replicate. This cost associated with replication ultimately results in a deceleration in transmission rate because increasing within‐host replication increases host mortality. Empirical tests of predictions of the hypothesis have found mixed support, which cast doubt about its overall generalizability. To quantitatively address this issue, we conducted a meta‐analysis of 29 empirical studies, after reviewing over 6000 published papers, addressing the four core relationships between (1) virulence and recovery rate, (2) within‐host replication rate and virulence, (3) within‐host replication and transmission rate, and (4) virulence and transmission rate. We found strong support for an increasing relationship between replication and virulence, and replication and transmission. Yet, it is still uncertain if these relationships generally decelerate due to high within‐study variability. There was insufficient data to quantitatively test the other two core relationships predicted by the theory. Overall, the results suggest that the current empirical evidence provides partial support for the trade‐off hypothesis, but more work remains to be done.     

AN EXPERIMENTAL TEST OF THE TRANSMISSION‐VIRULENCE TRADE‐OFF HYPOTHESIS IN A PLANT VIRUS

The transmission–virulence trade‐off hypothesis is one of the few adaptive explanations of virulence evolution, and assumes that there is an overall positive correlation between parasite transmission and virulence. The shape of the transmission–virulence relationship predicts whether virulence should evolve toward either a maximum or to an intermediate optimum. A positive correlation between each of these traits and within‐host growth is often suggested to underlie the relationship between virulence and transmission. There are few experimental tests of this hypothesis; this study reports on the first empirical test on a plant pathogen. We infected Brassica rapa plants with nine natural isolates of Cauliflower mosaic virus and then estimated three traits: transmission, virulence, and within‐host viral accumulation. As predicted by the trade‐off hypothesis, we observed a positive correlation between transmission and virulence, suggestive of the existence of an intermediate optimum. We discovered the unexpected existence of two groups of within‐host accumulation, differing by at least an order of magnitude. When accumulation groups were not accounted for, within‐host accumulation was correlated neither to virulence nor transmission, although our results suggest that within each group these correlations exist.     

THE IMPACT OF SPATIAL SCALE AND HABITAT CONFIGURATION ON PATTERNS OF TRAIT VARIATION AND LOCAL ADAPTATION IN A WILD PLANT PARASITE

Theory indicates that spatial scale and habitat configuration are fundamental for coevolutionary dynamics and how diversity is maintained in host–pathogen interactions. Yet, we lack empirical data to translate the theory to natural host–parasite systems. In this study, we conduct a multiscale cross‐inoculation study using the specialist wild plant pathogen Podosphaera plantaginis on its host plant Plantago lanceolata. We apply the same sampling scheme to a region with highly fragmented (Åland) and continuous (Saaremaa) host populations. Although theory predicts higher parasite virulence in continuous regions, we did not detect differences in traits conferring virulence among the regions. Patterns of adaptation were highly scale dependent. We detected parasite maladaptation among regions, and among populations separated by intermediate distances (6.0–40.0 km) within the fragmented region. In contrast, parasite performance did not vary significantly according to host origin in the continuous landscape. For both regions, differentiation among populations was much larger for genetic variation than for phenotypic variation, indicating balancing selection maintaining phenotypic variation within populations. Our findings illustrate the critical role of spatial scale and habitat configuration in driving host–parasite coevolution. The absence of more aggressive strains in the continuous landscape, in contrast to theoretical predictions, has major implications for long‐term decision making in conservation, agriculture, and public health.     

Tracking changes in life‐history traits related to unnecessary virulence in a plant‐parasitic nematode

Evaluating trade‐offs in life‐history traits of plant pathogens is essential to understand the evolution and epidemiology of diseases. In particular, virulence costs when the corresponding host resistance gene is lacking play a major role in the adaptive biology of pathogens and contribute to the maintenance of their genetic diversity. Here, we investigated whether life‐history traits directly linked to the establishment of plant–nematode interactions, that is, ability to locate and move toward the roots of the host plant, and to invade roots and develop into mature females, are affected in Meloidogyne incognita lines virulent against the tomato Mi‐1.2 resistance gene. Virulent and avirulent near‐isogenic lines only differing in their capacity to reproduce or not on resistant tomatoes were compared in single inoculation or pairwise competition experiments. Data highlighted (1) a global lack of trade‐off in traits associated with unnecessary virulence with respect to the nematode ability to successfully infest plant roots and (2) variability in these traits when the genetic background of the nematode is considered irrespective of its (a)virulence status. These data suggest that the variation detected here is independent from the adaptation of M. incognita to host resistance, but rather reflects some genetic polymorphism in this asexual organism.     

GENETIC VARIATION IN RESISTANCE AND FECUNDITY TOLERANCE IN A NATURAL HOST–PATHOGEN INTERACTION

Individuals vary in their ability to defend against pathogens. Determining how natural selection maintains this variation is often difficult, in part because there are multiple ways that organisms defend themselves against pathogens. One important distinction is between mechanisms of resistance that fight off infection, and mechanisms of tolerance that limit the impact of infection on host fitness without influencing pathogen growth. Theory predicts variation among genotypes in resistance, but not necessarily in tolerance. Here, we study variation among pea aphid (Acyrthosiphon pisum) genotypes in defense against the fungal pathogen Pandora neoaphidis. It has been well established that pea aphids can harbor symbiotic bacteria that protect them from fungal pathogens. However, it is unclear whether aphid genotypes vary in defense against Pandora in the absence of protective symbionts. We therefore measured resistance and tolerance to fungal infection in aphid lines collected without symbionts, and found variation among lines in survival and in the percent of individuals that formed a sporulating cadaver. We also found evidence of variation in tolerance to the effects of pathogen infection on host fecundity, but no variation in tolerance of pathogen‐induced mortality. We discuss these findings in light of theoretical predictions about host‐pathogen coevolution.     

Host resistance and pathogen infectivity in host populations with varying connectivity

Theory predicts that hosts and pathogens will evolve higher resistance and aggressiveness in systems where populations are spatially connected than in situations in which populations are isolated and dispersal is more local. In a large cross‐inoculation experiment we surveyed patterns of host resistance and pathogen infectivity in anther‐smut diseased Viscaria alpina populations from three contrasting areas where populations range from continuous, through patchy but spatially connected to highly isolated demes. In agreement with theory, isolated populations of V. alpina were more susceptible on average than either patchily distributed or continuous populations. While increased dispersal in connected systems increases disease spread, it may also increase host gene flow and the potential for greater host resistance to evolve. In the Viscaria–Microbotryum system, pathogen infectivity mirrored patterns of host resistance with strains from the isolated populations being the least infective and strains from the more resistant continuous populations being the most infective on average, suggesting that high resistance selects for high infectivity. To our knowledge this study is the first to characterize the impacts of varying spatial connectivity on patterns of host resistance and pathogen infectivity in a natural system.     

Disease‐structured N‐mixture models: A practical guide to model disease dynamics using count data

Obtaining inferences on disease dynamics (e.g., host population size, pathogen prevalence, transmission rate, host survival probability) typically requires marking and tracking individuals over time. While multistate mark–recapture models can produce high‐quality inference, these techniques are difficult to employ at large spatial and long temporal scales or in small remnant host populations decimated by virulent pathogens, where low recapture rates may preclude the use of mark–recapture techniques. Recently developed N‐mixture models offer a statistical framework for estimating wildlife disease dynamics from count data. N‐mixture models are a type of state‐space model in which observation error is attributed to failing to detect some individuals when they are present (i.e., false negatives). The analysis approach uses repeated surveys of sites over a period of population closure to estimate detection probability. We review the challenges of modeling disease dynamics and describe how N‐mixture models can be used to estimate common metrics, including pathogen prevalence, transmission, and recovery rates while accounting for imperfect host and pathogen detection. We also offer a perspective on future research directions at the intersection of quantitative and disease ecology, including the estimation of false positives in pathogen presence, spatially explicit disease‐structured N‐mixture models, and the integration of other data types with count data to inform disease dynamics. Managers rely on accurate and precise estimates of disease dynamics to develop strategies to mitigate pathogen impacts on host populations. At a time when pathogens pose one of the greatest threats to biodiversity, statistical methods that lead to robust inferences on host populations are critically needed for rapid, rather than incremental, assessments of the impacts of emerging infectious diseases.     

Evolution of Drosophila resistance against different pathogens and infection routes entails no detectable maintenance costs

Pathogens exert a strong selective pressure on hosts, entailing host adaptation to infection. This adaptation often affects negatively other fitness‐related traits. Such trade‐offs may underlie the maintenance of genetic diversity for pathogen resistance. Trade‐offs can be tested with experimental evolution of host populations adapting to parasites, using two approaches: (1) measuring changes in immunocompetence in relaxed‐selection lines and (2) comparing life‐history traits of evolved and control lines in pathogen‐free environments. Here, we used both approaches to examine trade‐offs in Drosophila melanogaster populations evolving for over 30 generations under infection with Drosophila C Virus or the bacterium Pseudomonas entomophila, the latter through different routes. We find that resistance is maintained after up to 30 generations of relaxed selection. Moreover, no differences in several classical life‐history traits between control and evolved populations were found in pathogen‐free environments, even under stresses such as desiccation, nutrient limitation, and high densities. Hence, we did not detect any maintenance costs associated with resistance to pathogens. We hypothesize that extremely high selection pressures commonly used lead to the disproportionate expression of costs relative to their actual occurrence in natural systems. Still, the maintenance of genetic variation for pathogen resistance calls for an explanation.     

Evidence of trade‐offs shaping virulence evolution in an emerging wildlife pathogen

In the mid‐1990s, the common poultry pathogen Mycoplasma gallisepticum (MG) made a successful species jump to the eastern North American house finch Haemorhous mexicanus (HM). Subsequent strain diversification allows us to directly quantify, in an experimental setting, the transmission dynamics of three sequentially emergent geographic isolates of MG, which differ in the levels of pathogen load they induce. We find significant among‐strain variation in rates of transmission as well as recovery. Pathogen strains also differ in their induction of host morbidity, measured as the severity of eye lesions due to infection. Relationships between pathogen traits are also investigated, with transmission and recovery rates being significantly negatively correlated, whereas transmission and virulence, measured as average eye lesion score over the course of infection, are positively correlated. By quantifying these disease‐relevant parameters and their relationships, we provide the first analysis of the trade‐offs that shape the evolution of this important emerging pathogen.     

Linking anthropogenic resources to wildlife–pathogen dynamics: a review and meta‐analysis

Urbanisation and agriculture cause declines for many wildlife, but some species benefit from novel resources, especially food, provided in human‐dominated habitats. Resulting shifts in wildlife ecology can alter infectious disease dynamics and create opportunities for cross‐species transmission, yet predicting host–pathogen responses to resource provisioning is challenging. Factors enhancing transmission, such as increased aggregation, could be offset by better host immunity due to improved nutrition. Here, we conduct a review and meta‐analysis to show that food provisioning results in highly heterogeneous infection outcomes that depend on pathogen type and anthropogenic food source. We also find empirical support for behavioural and immune mechanisms through which human‐provided resources alter host exposure and tolerance to pathogens. A review of recent theoretical models of resource provisioning and infection dynamics shows that changes in host contact rates and immunity produce strong non‐linear responses in pathogen invasion and prevalence. By integrating results of our meta‐analysis back into a theoretical framework, we find provisioning amplifies pathogen invasion under increased host aggregation and tolerance, but reduces transmission if provisioned food decreases dietary exposure to parasites. These results carry implications for wildlife disease management and highlight areas for future work, such as how resource shifts might affect virulence evolution.     

Host–parasite coevolution: genetic variation in a virus population and the interaction with a host gene

Host–parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host‐specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major‐effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission‐blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.     

Social immunity modulates competition between coinfecting pathogens

Coinfections with multiple pathogens can result in complex within‐host dynamics affecting virulence and transmission. While multiple infections are intensively studied in solitary hosts, it is so far unresolved how social host interactions interfere with pathogen competition, and if this depends on coinfection diversity. We studied how the collective disease defences of ants – their social immunity – influence pathogen competition in coinfections of same or different fungal pathogen species. Social immunity reduced virulence for all pathogen combinations, but interfered with spore production only in different‐species coinfections. Here, it decreased overall pathogen sporulation success while increasing co‐sporulation on individual cadavers and maintaining a higher pathogen diversity at the community level. Mathematical modelling revealed that host sanitary care alone can modulate competitive outcomes between pathogens, giving advantage to fast‐germinating, thus less grooming‐sensitive ones. Host social interactions can hence modulate infection dynamics in coinfected group members, thereby altering pathogen communities at the host level and population level.     

Sex differences in the effects of juvenile and adult diet on age‐dependent reproductive effort

Sexual selection should cause sex differences in patterns of resource allocation. When current and future reproductive effort trade off, variation in resource acquisition might further cause sex differences in age‐dependent investment, or in sensitivity to changes in resource availability over time. However, the nature and prevalence of sex differences in age‐dependent investment remain unclear. We manipulated resource acquisition at juvenile and adult stages in decorated crickets, Gryllodes sigillatus, and assessed effects on sex‐specific allocation to age‐dependent reproductive effort (calling in males, fecundity in females) and longevity. We predicted that the resource and time demands of egg production would result in relatively consistent female strategies across treatments, whereas male investment should depend sharply on diet. Contrary to expectations, female age‐dependent reproductive effort diverged substantially across treatments, with resource‐limited females showing much lower and later investment in reproduction; the highest fecundity was associated with intermediate lifespans. In contrast, long‐lived males always signalled more than short‐lived males, and male age‐dependent reproductive effort did not depend on diet. We found consistently positive covariance between male reproductive effort and lifespan, whereas diet altered this covariance in females, revealing sex differences in the benefits of allocation to longevity. Our results support sex‐specific selection on allocation patterns, but also suggest a simpler alternative: males may use social feedback to make allocation decisions and preferentially store resources as energetic reserves in its absence. Increased calling effort with age therefore could be caused by gradual resource accumulation, heightened mortality risk over time, and a lack of feedback from available mates.     

Linking predator–prey interactions with exposure to a trophically transmitted parasite using PCR‐based analyses

Parasite transmission is determined by the rate of contact between a susceptible host and an infective stage and susceptibility to infection given an exposure event. Attempts to measure levels of variation in exposure in natural populations can be especially challenging. The level of exposure to a major class of parasites, trophically transmitted parasites, can be estimated by investigating the host's feeding behaviour. Since the parasites rely on the ingestion of infective intermediate hosts for transmission, the potential for exposure to infection is inherently linked to the definitive host's feeding ecology. Here, we combined epidemiological data and molecular analyses (polymerase chain reaction) of the diet of the definitive host, the white‐footed mouse (Peromyscus leucopus), to investigate temporal and individual heterogeneities in exposure to infection. Our results show that the consumption of cricket intermediate hosts accounted for much of the variation in infection; mice that had consumed crickets were four times more likely to become infected than animals that tested negative for cricket DNA. In particular, pregnant female hosts were three times more likely to consume crickets, which corresponded to a threefold increase in infection compared with nonpregnant females. Interestingly, males in breeding condition had a higher rate of infection even though breeding males were just as likely to test positive for cricket consumption as nonbreeding males. These results suggest that while heterogeneity in host diet served as a strong predictor of exposure risk, differential susceptibility to infection may also play a key role, particularly among male hosts. By combining PCR analyses with epidemiological data, we revealed temporal variation in exposure through prey consumption and identified potentially important individual heterogeneities in parasite transmission.