Evolutionary implications of host–pathogen specificity: the fitness consequences of host life history traits

Pathogens and parasites can be strong agents of selection, and often exhibit some degree of genetic specificity for individual host strains. Here we show that this host–pathogen specificity can affect the evolution of host life history traits. All else equal, evolution should select for genes that increase individuals' reproduction rates or lifespans (and thus total reproduction per individual). Using a simple host–pathogen model, we show that when the genetic specificity of pathogen infection is low, host strains with higher reproduction rates or longer lifespans drive slower-reproducing or shorter-lived host strains to extinction, as one would expect. However, when pathogens exhibit specificity for host strains with different life history traits, the evolutionary advantages of these traits can be greatly diminished by pathogen-mediated selection. Given sufficient host–pathogen specificity, pathogen-mediated selection can maintain polymorphism in host traits that are correlated with pathogen resistance traits, despite large intrinsic fitness differences among host strains. These results have two important implications. First, selection on host life history traits will be weaker than expected, whenever host fitness is significantly affected by genotype-specific pathogen attack. Second, where polymorphism in host traits is maintained by pathogen-mediated selection, preserving the genetic diversity of host species may require preserving their pathogens as well. This revised version was published online in November 2006 with corrections to the Cover Date.     

The potential for rust infection to cause natural selection in apomictic Arabis holboellii (Brassicaceae)

Few studies have examined the potential for pathogens with complex life cycles to cause selection on their required alternate (=intermediate) hosts. Here we examine the effects of two fungal pathogens on an herbaceous mustard, Arabis holboellii. One pathogen species uses A. holboellii as a primary host, the other uses it as an alternate host. This plant-pathogen system is especially interesting because the host, A. holboellii, is apomictic; thus individuals reproduce exact copies of themselves. Despite this mode of reproduction, A. holboellii populations are surprisingly genetically diverse. Could frequency dependent selection by pathogens be maintaining clonal diversity? This study assesses the potential for selection by pathogens. In a controlled greehouse experiment we show that there is heritable variation in A. holboellii's resistance to the rust, Puccinia monoica, and that host fitness is severely reduced by P. monoica infection in both the greenhouse and under natural conditions. Field observations indicate that host clones are also differentially susceptible to the short-cycled rust, P. thlaspeos, and that host fitness is reduced by infection to this pathogen as well. Although the preconditions for pathogen-mediated selection are present, frequency-dependent selection by pathogens is unlikely to be important in structuring populations of Arabis holboellii because multiple host genotypes are susceptible to the same inoculum and the pathogen has a long generation time.     

A gravity model for the spread of a pollinator-borne plant pathogen

Many pathogens of plants are transmitted by arthropod vectors whose movement between individual hosts is influenced by foraging behavior. Insect foraging has been shown to depend on both the quality of hosts and the distances between hosts. Given the spatial distribution of host plants and individual variation in quality, vector foraging patterns may therefore produce predictable variation in exposure to pathogens. We develop a "gravity" model to describe the spatial spread of a vector-borne plant pathogen from underlying models of insect foraging in response to host quality using the pollinator-borne smut fungus Microbotryum violaceum as a case study. We fit the model to spatially explicit time series of M. violaceum transmission in replicate experimental plots of the white campion Silene latifolia. The gravity model provides a better fit than a mean field model or a model with only distance-dependent transmission. The results highlight the importance of active vector foraging in generating spatial patterns of disease incidence and for pathogen-mediated selection for floral traits.     

Ecosystem dynamics, biological diversity and emerging infectious diseases

In this article, we summarize the major scientific developments of the last decade on the transmission of infectious agents in multi-host systems. Almost sixty percent of the pathogens that have emerged in humans during the last 30-40 years are of animal origin and about sixty percent of them show an important variety of host species besides humans (3 or more possible host species). In this review, we focus on zoonotic infections with vector-borne transmission and dissect the contrasting effects that a multiplicity of host reservoirs and vectors can have on their disease dynamics. We discuss the effects exerted by host and vector species richness and composition on pathogen prevalence (i.e., reduction, including the dilution effect, or amplification). We emphasize that, in multiple host systems and for vector-borne zoonotic pathogens, host reservoir species and vector species can exert contrasting effect locally. The outcome on disease dynamics (reduced pathogen prevalence in vectors when the host reservoir species is rich and increased pathogen prevalence when the vector species richness increases) may be highly heterogeneous in both space and time. We then ask briefly how a shift towards a more systemic perspective in the study of emerging infectious diseases, which are driven by a multiplicity of hosts, may stimulate further research developments. Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective.     

Pathogens and sex in plants

Summary Extant theories that attribute the evolution of sex to pathogen attack depend on the assumption that pathogens are narrowly specialized, so that high fitness on one host genotype results in poor fitness on hosts with other allele combinations. This assumption is necessary in order for frequency-dependent selection to produce sustained cycling of gametic disequilibrium across the host's disease resistance loci, which makes recombination advantageous. However, a review of numerous genetic studies on plant disease resistance failed to uncover a single example consistent with this assumption. Instead, the empirical results provide strong support for a different pattern of pathogen specificity, in which adaptation by pathogens to one resistance allele does not preclude high fitness on alternate host genotypes lacking that allele. Modification of traditional models for pathogen-mediated evolution of sex showed that for conditions close to the empirical pattern of genotypic specificity, sex is almost never favoured. For plants, these results cast doubt on current theories arguing that pathogens are the primary selective agent responsible for sexual reproduction.     

Biogeographical patterns and co-occurrence of pathogenic infection across island populations of Berthelot’s pipit (<Emphasis Type="Italic">Anthus berthelotii</Emphasis>)

Pathogens can exert strong selective forces upon host populations. However, before we can make any predictions about the consequences of pathogen-mediated selection, we first need to determine whether patterns of pathogen distribution are consistent over spatiotemporal scales. We used molecular techniques to screen for a variety of blood pathogens (avian malaria, pox and trypanosomes) over a three-year time period across 13 island populations of the Berthelot’s pipit (Anthus berthelotii). This species has only recently dispersed across its range in the North Atlantic, with little subsequent migration, providing an ideal opportunity to examine the causes and effects of pathogenic infection in populations in the early stages of differentiation. We screened 832 individuals, and identified two strains of Plasmodium, four strains of Leucocytozoon, and one pox strain. We found strong differences in pathogen prevalence across populations, ranging from 0 to 65%, and while some fluctuations in prevalence occurred, these differences were largely stable over the time period studied. Smaller, more isolated islands harboured fewer pathogen strains than larger, less isolated islands, indicating that at the population level, colonization and extinction play an important role in determining pathogen distribution. Individual-level analyses confirmed the island effect, and also revealed a positive association between Plasmodium and pox infection, which could have arisen due to dual transmission of the pathogens by the same vectors, or because one pathogen lowers resistance to the other. Our findings, combined with an effect of infection on host body condition, suggest that Berthelot’s pipits are subject to different levels of pathogen-mediated selection both across and within populations, and that these selective pressures are consistent over time.     

Niche‐based host extinction increases prevalence of an environmentally acquired pathogen

Understanding the ecology of environmentally acquired and multi‐host pathogens affecting humans and wildlife has been elusive in part because fluctuations in the abundance of host and pathogen species may feed back onto pathogen transmission. Complexity of pathogen‐host dynamics emerges from processes driving local extinction of the pathogen, its hosts and non‐hosts. While the extinction of species may entail losses in pathogen–host interactions and decrease the proportion of hosts infected by a pathogen (prevalence), some studies suggest the opposite pattern. Niche‐based extinction, based on the species tolerance to environmental conditions, may increase prevalence of infection because the pathogen and its hosts persist, while other species go extinct. Hence, understanding prevalence of infection requires disentangling random‐ and niche‐based extinction processes occurring simultaneously. To contribute to this exercise, we analysed the prevalence of an environmentally acquired, multi‐host pathogen, Mycobacterium ulcerans (MU), in a unique dataset of 16 communities of freshwater animals, surveyed during 12 months in Akonolinga, Cameroon in equatorial Africa. Two different ecosystems were identified: rivers (lotic) and swamps and flooded areas (lentic). Increased prevalence of MU infection was correlated with niche‐based extinction of aquatic host invertebrates and vertebrates in the lentic ecosystems, whereas decreased prevalence was associated with random disassembly of the lotic ecosystems. This finding suggests that random and niche‐based extinction of host taxa are key to assessing the effect of local extinction of species on the ecology of environmentally acquired and multi‐host pathogens.     

Solving the Wolbachia paradox: modeling the tripartite interaction between host, Wolbachia, and a natural enemy

Wolbachia is one of the most common symbionts of arthropods. Its establishment requires lateral transfer to and successful transmission within novel host species. However, Wolbachia performs poorly when introduced into new host species, and models predict that Wolbachia should seldom be able to establish from low initial frequencies. Recently, various symbionts, including Wolbachia, have been shown to protect their hosts from natural enemies. Hence, Wolbachia invasion may be facilitated by the dynamic interaction between it, its host, and a natural enemy. We model such an interaction whereby Wolbachia induces either complete resistance, partial resistance, or tolerance to a host-specific pathogen and also induces the common manipulation phenotype of cytoplasmic incompatibility (CI). We show that the presence of the pathogen greatly facilitates Wolbachia invasion from rare and widens the parameter space in which "imperfect" Wolbachia strains can invade. Furthermore, positive frequency-dependent selection through CI can drive Wolbachia to very high frequencies, potentially excluding the pathogen. These results may explain a poorly understood aspect of Wolbachia biology: it is widespread, despite performing poorly after transfer to new host species. They also support the intriguing possibility that Wolbachia strains that encode both CI and natural-enemy resistance could potentially rid insects, including human disease vectors, of important pathogens.     

Forest species diversity reduces disease risk in a generalist plant pathogen invasion

Empirical evidence suggests that biodiversity loss can increase disease transmission, yet our understanding of the 'diversity-disease hypothesis' for generalist pathogens in natural ecosystems is limited. We used a landscape epidemiological approach to examine two scenarios regarding diversity effects on the emerging plant pathogen Phytophthora ramorum across a broad, heterogeneous ecoregion: (1) an amplification effect exists where disease risk is greater in areas with higher plant diversity due to the pathogen's wide host range, or (2) a dilution effect where risk is reduced with increasing diversity due to lower competency of alternative hosts. We found evidence for pathogen dilution, whereby disease risk was lower in sites with higher species diversity, after accounting for potentially confounding effects of host density and landscape heterogeneity. Our results suggest that although nearly all plants in the ecosystem are hosts, alternative hosts may dilute disease transmission by competent hosts, thereby buffering forest health from infectious disease.     

Pathogens manipulate the preference of vectors,slowing disease spread in a multi‐host system

The spread of vector‐borne pathogens depends on a complex set of interactions among pathogen, vector, and host. In single‐host systems, pathogens can induce changes in vector preferences for infected vs. healthy hosts. Yet it is unclear if pathogens also induce changes in vector preference among host species, and how changes in vector behaviour alter the ecological dynamics of disease spread. Here, we couple multi‐host preference experiments with a novel model of vector preference general to both single and multi‐host communities. We show that viruliferous aphids exhibit strong preferences for healthy and long‐lived hosts. Coupling experimental results with modelling to account for preference leads to a strong decrease in overall pathogen spread through multi‐host communities due to non‐random sorting of viruliferous vectors between preferred and non‐preferred host species. Our results demonstrate the importance of the interplay between vector behaviour and host diversity as a key mechanism in the spread of vectored‐diseases.     

Imperfect vaccines and the evolution of pathogens causing acute infections in vertebrates

A study by Gandon et al. (2001) considered the potential ways pathogens may evolve in response to vaccination with imperfect vaccines. In this paper, by focusing on acute infections of vertebrate hosts, we examine whether imperfect vaccines that do not completely block a pathogen's replication (antigrowth) or transmission (antitransmission) may lead to evolution of more or less virulent pathogen strains. To address this question, we use models of the within-host dynamics of the pathogen and the host's immune responses. One advantage of the use of this within-host approach is that vaccination can be easily incorporated in the models and the trade-offs between pathogen transmissibility, host recovery, and virulence that drive evolution of pathogens in these models can be easily estimated. We find that the use of either antigrowth or antitransmission vaccines leads to the evolution of pathogens with an increased within-host growth rate; infection of unvaccinated hosts with such evolved pathogens results in high host mortality and low pathogen transmission. Vaccination of only a fraction of hosts with antigrowth vaccines may prevent pathogens from evolving high virulence due to pathogen adaptation to unvaccinated hosts and thus protection of vaccinated hosts from pathogen-induced disease. In contrast, antitransmission vaccines may be beneficial only if they are effective enough to cause pathogen extinction. Our results suggest that particular mechanisms of action of vaccines and their efficacy are crucial in predicting longterm evolutionary consequences of the use of imperfect vaccines.     

Effects of species diversity on disease risk

The transmission of infectious diseases is an inherently ecological process involving interactions among at least two, and often many, species. Not surprisingly, then, the species diversity of ecological communities can potentially affect the prevalence of infectious diseases. Although a number of studies have now identified effects of diversity on disease prevalence, the mechanisms underlying these effects remain unclear in many cases. Starting with simple epidemiological models, we describe a suite of mechanisms through which diversity could increase or decrease disease risk, and illustrate the potential applicability of these mechanisms for both vector-borne and non-vector-borne diseases, and for both specialist and generalist pathogens. We review examples of how these mechanisms may operate in specific disease systems. Because the effects of diversity on multi-host disease systems have been the subject of much recent research and controversy, we describe several recent efforts to delineate under what general conditions host diversity should increase or decrease disease prevalence, and illustrate these with examples. Both models and literature reviews suggest that high host diversity is more likely to decrease than increase disease risk. Reduced disease risk with increasing host diversity is especially likely when pathogen transmission is frequency-dependent, and when pathogen transmission is greater within species than between species, particularly when the most competent hosts are also relatively abundant and widespread. We conclude by identifying focal areas for future research, including (1) describing patterns of change in disease risk with changing diversity; (2) identifying the mechanisms responsible for observed changes in risk; (3) clarifying additional mechanisms in a wider range of epidemiological models; and (4) experimentally manipulating disease systems to assess the impact of proposed mechanisms.     

Richness and Composition of Niche-Assembled Viral Pathogen Communities

The pathogen and parasite community that inhabits every free-living organism can control host vital rates including lifespan and reproductive output. To date, however, there have been few experiments examining pathogen community assembly replicated at large-enough spatial scales to inform our understanding of pathogen dynamics in natural systems. Pathogen community assembly may be driven by neutral stochastic colonization and extinction events or by niche differentiation that constrains pathogen distributions to particular environmental conditions, hosts, or vectors.Here, we present results from a regionally-replicated experiment investigating the community of barley and cereal yellow dwarf viruses (B/CYDV''s) in over 5000 experimentally planted individuals of six grass species along a 700 km latitudinal gradient along the Pacific coast of North America (USA) in response to experimentally manipulated nitrogen and phosphorus supplies. The composition of the virus community varied predictably among hosts and across nutrient-addition treatments, indicating niche differentiation among virus species. There were some concordant responses among the viral species. For example, the prevalence of most viral species increased consistently with perennial grass cover, leading to a 60% increase in the richness of the viral community within individual hosts (i.e., coinfection) in perennial-dominated plots. Furthermore, infection rates of the six host species in the field were highly correlated with vector preferences assessed in laboratory trials. Our results reveal the importance of niche differentiation in structuring virus assemblages. Virus species distributions reflected a combination of local host community composition, host species-specific vector preferences, and virus responses to host nutrition. In addition, our results suggest that heterogeneity among host species in their capacity to attract vectors or support pathogens between growing seasons can lead to positive covariation among virus species.     

The phylogenetic range of bacterial and viral pathogens of vertebrates

Many major human pathogens are multihost pathogens, able to infect other vertebrate species. Describing the general patterns of host–pathogen associations across pathogen taxa is therefore important to understand risk factors for human disease emergence. However, there is a lack of comprehensive curated databases for this purpose, with most previous efforts focusing on viruses. Here, we report the largest manually compiled host–pathogen association database, covering 2,595 bacteria and viruses infecting 2,656 vertebrate hosts. We also build a tree for host species using nine mitochondrial genes, giving a quantitative measure of the phylogenetic similarity of hosts. We find that the majority of bacteria and viruses are specialists infecting only a single host species, with bacteria having a significantly higher proportion of specialists compared to viruses. Conversely, multihost viruses have a more restricted host range than multihost bacteria. We perform multiple analyses of factors associated with pathogen richness per host species and the pathogen traits associated with greater host range and zoonotic potential. We show that factors previously identified as important for zoonotic potential in viruses—such as phylogenetic range, research effort, and being vector‐borne—are also predictive in bacteria. We find that the fraction of pathogens shared between two hosts decreases with the phylogenetic distance between them. Our results suggest that host phylogenetic similarity is the primary factor for host‐switching in pathogens.     

The evolution of virulence in pathogens with frequency-dependent transmission

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.     

Microbiome influences on insect host vector competence

Insect symbioses lack the complexity and diversity of those associated with higher eukaryotic hosts. Symbiotic microbiomes are beneficial to their insect hosts in many ways, including dietary supplementation, tolerance to environmental perturbations and maintenance and/or enhancement of host immune system homeostasis. Recent studies have also highlighted the importance of the microbiome in the context of host pathogen transmission processes. Here we provide an overview of the relationship between insect disease vectors, such as tsetse flies and mosquitoes, and their associated microbiome. Several mechanisms are discussed through which symbiotic microbes can influence the ability of their host to transmit pathogens, as well as potential disease control strategies that harness symbiotic microbes to reduce pathogen transmission through an insect vector.     

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.     

Restriction of Francisella novicida Genetic Diversity during Infection of the Vector Midgut

The genetic diversity of pathogens, and interactions between genotypes, can strongly influence pathogen phenotypes such as transmissibility and virulence. For vector-borne pathogens, both mammalian hosts and arthropod vectors may limit pathogen genotypic diversity (number of unique genotypes circulating in an area) by preventing infection or transmission of particular genotypes. Mammalian hosts often act as “ecological filters” for pathogen diversity, where novel variants are frequently eliminated because of stochastic events or fitness costs. However, whether vectors can serve a similar role in limiting pathogen diversity is less clear. Here we show using Francisella novicida and a natural tick vector of Francisella spp. (Dermacentor andersoni), that the tick vector acted as a stronger ecological filter for pathogen diversity compared to the mammalian host. When both mice and ticks were exposed to mixtures of F. novicida genotypes, significantly fewer genotypes co-colonized ticks compared to mice. In both ticks and mice, increased genotypic diversity negatively affected the recovery of available genotypes. Competition among genotypes contributed to the reduction of diversity during infection of the tick midgut, as genotypes not recovered from tick midguts during mixed genotype infections were recovered from tick midguts during individual genotype infection. Mediated by stochastic and selective forces, pathogen genotype diversity was markedly reduced in the tick. We incorporated our experimental results into a model to demonstrate how vector population dynamics, especially vector-to-host ratio, strongly affected pathogen genotypic diversity in a population over time. Understanding pathogen genotypic population dynamics will aid in identification of the variables that most strongly affect pathogen transmission and disease ecology.     

A field test of the dilution effect hypothesis in four avian multi-host pathogens

The Dilution Effect Hypothesis (DEH) argues that greater biodiversity lowers the risk of disease and reduces the rates of pathogen transmission since more diverse communities harbour fewer competent hosts for any given pathogen, thereby reducing host exposure to the pathogen. DEH is expected to operate most intensely in vector-borne pathogens and when species-rich communities are not associated with increased host density. Overall, dilution will occur if greater species diversity leads to a lower contact rate between infected vectors and susceptible hosts, and between infected hosts and susceptible vectors. Field-based tests simultaneously analysing the prevalence of several multi-host pathogens in relation to host and vector diversity are required to validate DEH. We tested the relationship between the prevalence in house sparrows (Passer domesticus) of four vector-borne pathogens–three avian haemosporidians (including the avian malaria parasite Plasmodium and the malaria-like parasites Haemoproteus and Leucocytozoon) and West Nile virus (WNV)–and vertebrate diversity. Birds were sampled at 45 localities in SW Spain for which extensive data on vector (mosquitoes) and vertebrate communities exist. Vertebrate censuses were conducted to quantify avian and mammal density, species richness and evenness. Contrary to the predictions of DEH, WNV seroprevalence and haemosporidian prevalence were not negatively associated with either vertebrate species richness or evenness. Indeed, the opposite pattern was found, with positive relationships between avian species richness and WNV seroprevalence, and Leucocytozoon prevalence being detected. When vector (mosquito) richness and evenness were incorporated into the models, all the previous associations between WNV prevalence and the vertebrate community variables remained unchanged. No significant association was found for Plasmodium prevalence and vertebrate community variables in any of the models tested. Despite the studied system having several characteristics that should favour the dilution effect (i.e., vector-borne pathogens, an area where vector and host densities are unrelated, and where host richness is not associated with an increase in host density), none of the relationships between host species diversity and species richness, and pathogen prevalence supported DEH and, in fact, amplification was found for three of the four pathogens tested. Consequently, the range of pathogens and communities studied needs to be broadened if we are to understand the ecological factors that favour dilution and how often these conditions occur in nature.