Evolution Of Parasite Virulence Research Articles

Hyperparasitism and the evolution of parasite virulence.

Hyperparasites (species which parasitize other parasites) are common in natural populations, affecting many parasitic taxa, including: eukaryotic parasites; bacterial and fungal pathogens. Hyperparasitism is therefore likely to shape the ecology and evolution of many host-parasite systems, representing a promising method for biocontrol (e.g., treating antimicrobial resistant infections). However, the eco-evolutionary consequences of hyperparasitism have received little attention. We use a host-parasite-hyperparasite model to explore how introducing a hyperparasite drives the evolution of parasite virulence, and what impact this has on the host population. We show when the introduction of a hyperparasite selects for higher or lower parasite virulence, and the changes in virulence experienced by the host population. Crucially, we show that variation in the direct effects of hyperparasites on virulence and transmission, and the probability of cotransmission, can lead to a previously unseen hysteresis effect, whereby small shifts in hyperparasite characteristics can lead to sudden shifts in parasite virulence. We also show that hyperparasites can induce diversification in parasite virulence, leading to the coexistence of high and low virulence strains. Our results show hyperparasites can have dramatic effects on the evolution of parasite virulence, and that the use of hyperparasites in biocontrol should be approached with caution.

The evolution of parasite virulence under targeted culling and harvesting in wildlife and livestock.

There is a clear need to understand the effect of human intervention on the evolution of infectious disease. In particular, culling and harvesting of both wildlife and managed livestock populations are carried out in a wide range of management practices, and they have the potential to impact the evolution of a broad range of disease characteristics. Applying eco-evolutionary theory we show that once culling/harvesting becomes targeted on specific disease classes, the established result that culling selects for higher virulence is only found when sufficient infected individuals are culled. If susceptible or recovered individuals are targeted, selection for lower virulence can occur. An important implication of this result is that when culling to eradicate an infectious disease from a population, while it is optimal to target infected individuals, the consequent evolution can increase the basic reproductive ratio of the infection, , and make parasite eradication more difficult. We show that increases in evolved virulence due to the culling of infected individuals can lead to excess population decline when sustainably harvesting a population. In contrast, culling susceptible or recovered individuals can select for decreased virulence and a reduction in population decline through culling. The implications to the evolution of virulence are typically the same in wildlife populations, that are regulated by the parasite, and livestock populations, that have a constant population size where restocking balances the losses due to mortality. However, the well-known result that vertical transmission selects for lower virulence and transmission in wildlife populations is less marked in livestock populations for parasites that convey long-term immunity since restocking can enhance the density of the immune class. Our work emphasizes the importance of understanding the evolutionary consequences of intervention strategies and the different ecological feedbacks that can occur in wildlife and livestock populations.

Tolerance-conferring defensive symbionts and the evolution of parasite virulence.

Defensive symbionts in the host microbiome can confer protection from infection or reduce the harms of being infected by a parasite. Defensive symbionts are therefore promising agents of biocontrol that could be used to control or ameliorate the impact of infectious diseases. Previous theory has shown how symbionts can evolve along the parasitism-mutualism continuum to confer greater or lesser protection to their hosts and in turn how hosts may coevolve with their symbionts to potentially form a mutualistic relationship. However, the consequences of introducing a defensive symbiont for parasite evolution and how the symbiont may coevolve with the parasite have received relatively little theoretical attention. Here, we investigate the ecological and evolutionary implications of introducing a tolerance-conferring defensive symbiont into an established host-parasite system. We show that while the defensive symbiont may initially have a positive impact on the host population, parasite and symbiont evolution tend to have a net negative effect on the host population in the long term. This is because the introduction of the defensive symbiont always selects for an increase in parasite virulence and may cause diversification into high- and low-virulence strains. Even if the symbiont experiences selection for greater host protection, this simply increases selection for virulence in the parasite, resulting in a net negative effect on the host population. Our results therefore suggest that tolerance-conferring defensive symbionts may be poor biocontrol agents for population-level infectious disease control.

Interspecific host competition and parasite virulence evolution.

Virulence, the harm to hosts caused by parasite infection, can be selected for by several ecological factors acting synergistically or antagonistically. Here, we focus on the potential for interspecific host competition to shape virulence through such a network of effects. We first summarize how host natural mortality, body mass changes, population density and community diversity affect virulence evolution. We then introduce an initial conceptual framework highlighting how these host factors, which change during host competition, may drive virulence evolution via impacts on life-history trade-offs. We argue that the multi-faceted nature of both interspecific host competition and virulence evolution still requires consideration and experimentation to disentangle contrasting mechanisms. It also necessitates a differential treatment for parasites with various transmission strategies. However, such a comprehensive approach focusing on the role of interspecific host competition is essential to understand the processes driving the evolution of virulence in a tangled bank.

Coevolutionary Dynamics of Host Immune and Parasite Virulence Based on an Age-Structured Epidemic Model

Hosts can activate a defensive response to clear the parasite once being infected. To explore how host survival and fecundity are affected by host-parasite coevolution for chronic parasitic diseases, in this paper, we proposed an age-structured epidemic model with infection age, in which the parasite transmission rate and parasite-induced mortality rate are structured by the infection age. By use of critical function analysis method, we obtained the existence of the host immune evolutionary singular strategy which is a continuous singular strategy (CSS). Assume that parasite-induced mortality begins at infection age [Formula: see text] and is constant v thereafter. We got that the value of the CSS, [Formula: see text], monotonically decreases with respect to infection age [Formula: see text] (see Case (I)), while it is non-monotone if the constant v positively depends on the immune trait c (see Case (II)). This non-monotonicity is verified by numerical simulations and implies that the direction of immune evolution depends on the initial value of immune trait. Besides that, we adopted two special forms of the parasite transmission rate to study the parasite's virulence evolution, by maximizing the basic reproduction ratio [Formula: see text]. The values of the convergence stable parasite's virulence evolutionary singular strategies [Formula: see text] and [Formula: see text] increase monotonically with respect to time lag L (i.e., the time lag between the onset of transmission and mortality). At the singular strategy [Formula: see text] and [Formula: see text], we further obtained the expressions of the case mortalities [Formula: see text] and how they are affected by the time lag L. Finally, we only presented some preliminary results about host and parasite coevolution dynamics, including a general condition under which the coevolutionary singular strategy [Formula: see text] is evolutionarily stable.

The scale of competition impacts parasite virulence evolution

The structure of parasite populations can have important consequences for virulence evolution. Both the scale of competition, whether it is more intense in the within versus between host environment, and the mode of transmission, whether parasites transmit alone or in groups between hosts, influence population structure and can select for changes in virulence.In a selection experiment, we evolved metapopulations of the spider mite parasite Tetranychus urticae, under local (fixed sampling per host patch) or global (sampling determined by host patch productivity) competition, with either co- (with a female parasite from the same host patch) or random (with parasites from different host patches) transmission. After 33 generations of evolution, the fecundity and virulence of each replicate population was measured.Females from the ‘local-random’ regime were more virulent with higher fecundity than females from the ‘global-random’ regime. There was no difference in virulence or fecundity between females from the ‘global-random’ or ‘global co-transmission’ selection regimes.These results show that the scale of competition, and not the type of transmission, impacted virulence evolution for T. urticae. Local competition may maintain higher levels of genetic diversity at the level of the metapopulation. As such, intense local, within-host, competition selected for more productive individuals better able to exploit their environment and be the one to transmit to a new host.

Genome-enabled discovery of candidate virulence loci in Striga hermonthica, a devastating parasite of African cereal crops.

Parasites have evolved proteins, virulence factors (VFs), that facilitate plant colonisation, however VFs mediating parasitic plant-host interactions are poorly understood. Striga hermonthica is an obligate, root-parasitic plant of cereal hosts in sub-Saharan Africa, causing devastating yield losses. Understanding the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding resistance and delaying the evolution of parasite virulence. We assembled the S. hermonthica genome and identified secreted proteins using in silico prediction. Pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host allowed us to scan for loci where selection imposed by the resistant host had elevated the frequency of alleles contributing to successful colonisation. Thirty-eight putatively secreted VFs had very different allele frequencies with functions including host cell wall modification, protease or protease inhibitor and kinase activities. These candidate loci had significantly higher Tajima's D than the genomic background, consistent with balancing selection. Our results reveal diverse strategies used by S. hermonthica to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as part of a sustainable control strategy.

Host phenology can drive the evolution of intermediate virulence strategies in some obligate-killer parasites.

Traditional mechanistic trade‐offs between transmission and virulence are the foundation of nearly all theory on parasite virulence evolution. For obligate‐host killer parasites, evolution toward intermediate virulence depends on a trade‐off between virulence (time to death) and transmission (the number of progeny released upon death). Although several ecological factors impact optimal virulence strategies constrained by trade‐offs, these factors have been insufficient to explain the intermediate virulence levels observed in nature. The timing of seasonal activity, or phenology, is a factor that commonly influences ecological interactions but is difficult to incorporate into virulence evolution studies. We present a mathematical model of a seasonal obligate‐killer parasite to study the impact of host phenology on virulence evolution. The model demonstrates that host phenology can select for intermediate parasite virulence even when a traditional mechanistic trade‐off between transmission and virulence is omitted. The optimal virulence strategy is impacted by both the host activity period duration and the host emergence timing variation. Parasites with lower virulence strategies are favored in environments with longer host activity periods and when hosts emerge synchronously. The results demonstrate that host phenology can be sufficient to select for intermediate virulence strategies, providing an alternative driver of virulence evolution in some natural systems.

Effects of an alternative host on the prevalence and intensity of infection of a bumble bee parasite.

Several bee parasites are transmitted through flowers, and some of them can infect multiple host species. Given the shared use of flowers by bee species, parasites can potentially encounter multiple host species, which could affect the evolution of parasite virulence. We used the trypanosomatid parasite Crithidia bombi and its host, the common eastern bumble bee (Bombus impatiens), to explore the effect of infecting an alternative host, the alfalfa leaf-cutter bee (Megachile rotundata), on parasite infectivity and ability to replicate. We conducted a serial passage experiment on primary and alternative hosts, assessing infectivity and intensity of infection during five passes. Parasite cells from each pass through the alternative host were also used to infect a group of primary hosts. We found that serial passes through the alternative host increased infectivity, but there was no effect on intensity of infection. Interestingly, both the probability and intensity of infection on the primary host increased after serial passage through the alternative host. This increase in intensity of infection could be due to maladaptation after selection of new C. bombi strains has occurred in the alternative host. This study suggests that host switching has the potential to affect the adaptation of bee parasites to their hosts.

How parasite interaction strategies alter virulence evolution in multi-parasite communities.

The majority of organisms host multiple parasite species, each of which can interact with hosts and competitors through a diverse range of direct and indirect mechanisms. These within-host interactions can directly alter the mortality rate of coinfected hosts and alter the evolution of virulence (parasite-induced host mortality). Yet we still know little about how within-host interactions affect the evolution of parasite virulence in multi-parasite communities. Here, we modeled the virulence evolution of two coinfecting parasites in a host population in which parasites interacted through cross immunity, immune suppression, immunopathology, or spite. We show (1) that these within-host interactions have different effects on virulence evolution when all parasites interact with each other in the same way versus when coinfecting parasites have unique interaction strategies, (2) that these interactions cause the evolution of lower virulence in some hosts, and higher virulence in other hosts, depending on the hosts infection status, and (3) that for cross immunity and spite, whether parasites increase or decrease the evolutionarily stable virulence in coinfected hosts depended on interaction strength. These results improve our understanding of virulence evolution in complex parasite communities, and show that virulence evolution must be understood at the community scale.

How Individual Variation in Host Tolerance Affects Competence to Transmit Parasites

Tolerance, or the maintenance of host health or fitness at a given parasite burden, has often been studied in evolutionary and medical contexts, particularly with respect to effects on the evolution of parasite virulence and individual patient outcomes. These bodies of work have provided insight about tolerance for evolutionary phenomena (e.g., virulence) and individual health (e.g., recovering from an infection). However, due to the specific motivations of that work, few studies have considered the ecological ramifications of variation in tolerance, namely, how variation in forms of tolerance could mediate parasite movement through populations and even community-level disease dynamics. Tolerance is most commonly regarded as the relationship between host fitness and parasite burden. However, few if any studies have actually quantified host fitness, instead utilizing proxies of fitness as the response variables to be regressed against parasite burden. Here, we address how attention to the effects of parasite burden on traits that are relevant to host competence (i.e., the ability to amplify parasites to levels transmissible to other hosts/vectors) will enhance our understanding of disease dynamics in nature. We also provide several forms of guidance for how to overcome the challenges of quantifying tolerance in wild organisms.

The role of defensive symbionts in host-parasite coevolution.

Understanding the coevolution of hosts and parasites is a long-standing goal of evolutionary biology. There is a well-developed theoretical framework to describe the evolution of host-parasite interactions under the assumption of direct, two-species interactions, which can result in arms race dynamics or sustained genotype fluctuations driven by negative frequency dependence (Red Queen dynamics). However, many hosts rely on symbionts for defence against parasites. Whilst the ubiquity of defensive symbionts and their potential importance for disease control are increasingly recognized, there is still a gap in our understanding of how symbionts mediate or possibly take part in host-parasite coevolution. Herein we address this question by synthesizing information already available from theoretical and empirical studies. First, we briefly introduce current hypotheses on how defensive mutualisms evolved from more parasitic relationships and highlight exciting new experimental evidence showing that this can occur very rapidly. We go on to show that defensive symbionts influence virtually all important determinants of coevolutionary dynamics, namely the variation in host resistance available to selection by parasites, the specificity of host resistance, and the trade-off structure between host resistance and other components of fitness. In light of these findings, we turn to the limited theory and experiments available for such three-species interactions to assess the role of defensive symbionts in host-parasite coevolution. Specifically, we discuss under which conditions the defensive symbiont may take over from the host the reciprocal adaptation with parasites and undergo its own selection dynamics, thereby altering or relaxing selection on the hosts' own immune defences. Finally, we address potential effects of defensive symbionts on the evolution of parasite virulence. This is an important problem for which there is no single, clear-cut prediction. The selection on parasite virulence resulting from the presence of defensive symbionts in their hosts will depend on the underlying mechanism of defence. We identify the evolutionary predictions for different functional categories of symbiont-conferred resistance and we evaluate the empirical literature for supporting evidence. We end this review with outstanding questions and promising avenues for future research to improve our understanding of symbiont-mediated coevolution between hosts and parasites.

Next Generation Sequencing uncovers within-host differences in the genetic diversity of Cryptosporidium gp60 subtypes

The extent of within-host genetic diversity of parasites has implications for our understanding of the epidemiology, disease severity and evolution of parasite virulence. As with many other species, our understanding of the within-host diversity of the enteric parasite Cryptosporidium is changing. The present study compared Sanger and Next Generation Sequencing of glycoprotein 60 (gp60) amplicons from Cryptosporidium hominis (n=11), Cryptosporidium parvum (n=22) and Cryptosporidium cuniculus (n=8) DNA samples from Australia and China. Sanger sequencing identified only one gp60 subtype in each DNA sample: one C. hominis subtype (IbA10G2) (n=11), four C. parvum subtypes belonging to IIa (n=3) and IId (n=19) and one C. cuniculus subtype (VbA23) (n=8). Next Generation Sequencing identified the same subtypes initially identified by Sanger sequencing, but also identified additional gp60 subtypes in C. parvum and C. cuniculus but not in C. hominis, DNA samples. The number of C. parvum and C. cuniculus subtypes identified by Next Generation Sequencing within individual DNA samples ranged from two to four, and both C. parvum IIa and IId subtype families were identified within the one host in two samples. The finding of the present study has important implications for Cryptosporidium transmission tracking as well as vaccine and drug studies.

Highly potent host external immunity acts as a strong selective force enhancing rapid parasite virulence evolution.

Virulence is often under selection during host-parasite coevolution. In order to increase fitness, parasites are predicted to circumvent and overcome host immunity. A particular challenge for pathogens are external immune systems, chemical defence systems comprised of potent antimicrobial compounds released by prospective hosts into the environment. We carried out an evolution experiment, allowing for coevolution to occur, with the entomopathogenic fungus, Beauveria bassiana, and the red flour beetle, Tribolium castaneum, which has a well-documented external immune system with strong inhibitory effects against B. bassiana. After just seven transfers of experimental evolution we saw a significant increase in parasite induced host mortality, a proxy for virulence, in all B. bassiana lines. This apparent virulence increase was mainly the result of the B. bassiana lines evolving resistance to the beetles' external immune defences, not due to increased production of toxins or other harmful substances. Transcriptomic analyses of evolved B. bassiana implicated the up-regulation of oxidative stress resistance genes in the observed resistance to external immunity. It was concluded that external immunity acts as a powerful selective force for virulence evolution, with an increase in virulence being achieved apparently entirely by overcoming these defences, most likely due to elevated oxidative stress resistance.

A general model for the influence of immune priming on disease prevalence

Invertebrate immune priming, and other forms of innate immune memory in bacteria, plants, and mammals, modulate the post‐infection resistance, tolerance, and survival phenotypes of individuals previously exposed to microbes. By influencing the probability of both transmission and disease‐induced mortality, priming is likely to have a significant impact on disease dynamics. Two alternative models have been proposed as frameworks for the role of priming in infected populations, but the differences in their underlying key assumptions yield very different predictions for the effect of priming on disease dynamics. By examining these assumptions from the lens of within‐host dynamics, the model presented in this paper demonstrates that priming systems can be characterized along a continuous dose‐response gradient that unites these disparate frameworks. Moreover, it facilitates the incorporation of different kinds of immunological plasticity mechanisms, as well as the exposure probability and transmission characteristics of parasites. Simulating the interaction of these thresholds with the diversity of parasite life history strategies and distributions predicts that priming may actually inflate disease prevalence under certain conditions. Thus, priming of innate immune systems may act analogously to leaky vaccines and drive parasite virulence evolution. The results underscore the need for experimental studies that determine dose response curves for the both the probability of becoming primed following primary parasite exposure and shifts in resistance and tolerance in infected primed hosts. This framework is applicable to a variety of systems that show immunological memory.

Population structure of a vector-borne plant parasite.

Parasites are among the most diverse groups of life on Earth, yet complex natural histories often preclude studies of their speciation processes. The biology of parasitic plants facilitates insitu collection of data on both genetic structure and the mechanisms responsible for that structure. Here, we studied the role of mating, dispersal and establishment in host race formation of a parasitic plant. We investigated the population genetics of a vector-borne desert mistletoe (Phoradendron californicum) across two legume host tree species (Senegalia greggii and Prosopis velutina) in the Sonoran desert using microsatellites. Consistent with host race formation, we found strong host-associated genetic structure in sympatry, little genetic variation due to geographic site and weak isolation by distance. We hypothesize that genetic differentiation results from differences in the timing of mistletoe flowering by host species, as we found initial flowering date of individual mistletoes correlated with genetic ancestry. Hybrids with intermediate ancestry were detected genetically. Individuals likely resulting from recent, successful establishment events following dispersal between the host species were detected at frequencies similar to hybrids between host races. Therefore, barriers to gene flow between the host races may have been stronger at mating than at dispersal. We also found higher inbreeding and within-host individual relatedness values for mistletoes on the more rare and isolated host species (S.greggii). Our study spanned spatial scales to address how interactions with both vectors and hosts influence parasitic plant structure with implications for parasite virulence evolution and speciation.

Microsatellite genotyping and genome-wide single nucleotide polymorphism-based indices of Plasmodium falciparum diversity within clinical infections.

BackgroundIn regions where malaria is endemic, individuals are often infected with multiple distinct parasite genotypes, a situation that may impact on evolution of parasite virulence and drug resistance. Most approaches to studying genotypic diversity have involved analysis of a modest number of polymorphic loci, although whole genome sequencing enables a broader characterisation of samples.MethodsPCR-based microsatellite typing of a panel of ten loci was performed on Plasmodium falciparum in 95 clinical isolates from a highly endemic area in the Republic of Guinea, to characterize within-isolate genetic diversity. Separately, single nucleotide polymorphism (SNP) data from genome-wide short-read sequences of the same samples were used to derive within-isolate fixation indices (Fws), an inverse measure of diversity within each isolate compared to overall local genetic diversity. The latter indices were compared with the microsatellite results, and also with indices derived by randomly sampling modest numbers of SNPs.ResultsAs expected, the number of microsatellite loci with more than one allele in each isolate was highly significantly inversely correlated with the genome-wide Fws fixation index (r = −0.88, P < 0.001). However, the microsatellite analysis revealed that most isolates contained mixed genotypes, even those that had no detectable genome sequence heterogeneity. Random sampling of different numbers of SNPs showed that an Fws index derived from ten or more SNPs with minor allele frequencies of >10 % had high correlation (r > 0.90) with the index derived using all SNPs.ConclusionsDifferent types of data give highly correlated indices of within-infection diversity, although PCR-based analysis detects low-level minority genotypes not apparent in bulk sequence analysis. When whole-genome data are not obtainable, quantitative assay of ten or more SNPs can yield a reasonably accurate estimate of the within-infection fixation index (Fws).Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1324-4) contains supplementary material, which is available to authorized users.

Vaccine-driven evolution of parasite virulence and immune evasion in age-structured population: the case of pertussis

Despite enormous success of mass immunization programs in reducing incidence of infectious diseases, vaccine-escape strains have emerged perhaps as a consequence of strong selection pressures exerted on parasites by vaccines. Pertussis presents a well-documented example. As a childhood infection, it exhibits age-specific transmission biased to children. Assuming different transmission rates between children and adults, I study, by means of an age-structured epidemic model, evolutionary dynamics of parasite virulence in a vaccinated population. I find that the age-structure does not affect the evolutionary dynamics of parasite virulence. Also, based on empirical data reporting antigenic divergence with vaccine strains and mutations in virulence-associated genes in pertussis populations, I allow for parallel occurrence of mutations in parasite virulence and associated immune evasion. I conclude that this simultaneous adaptation of both traits may substantially alter the evolutionary course of the parasite. In particular, higher values of virulence are favoured once the parasite is able to evade the transmission-blocking vaccine-induced immunity. On the other hand, lower values of virulence are selected for once the parasite evolves the ability to evade the virulence-blocking vaccine-induced immunity. I emphasize the importance of multi-trait evolution to assess the direction of parasite adaptation more accurately.

Existing Infection Facilitates Establishment and Density of Malaria Parasites in Their Mosquito Vector.

Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito. Mixed infections contained more parasites but these larger populations did not have a detectable impact on vector survival. Together these results suggest that mosquitoes taking multiple infective bites may disproportionally contribute to malaria transmission. This will increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains. Moreover, control measures that reduce parasite prevalence in vertebrate hosts will reduce the likelihood of mosquitoes taking multiple infective feeds, and thus disproportionally reduce transmission. More generally, our study shows that the types of strain interactions detected in vertebrate hosts cannot necessarily be extrapolated to vectors.

Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.