Parasite host range and the evolution of host resistance

Parasite host range plays a pivotal role in the evolution and ecology of hosts and the emergence of infectious disease. Although the factors that promote host range and the epidemiological consequences of variation in host range are relatively well characterized, the effect of parasite host range on host resistance evolution is less well understood. In this study, we tested the impact of parasite host range on host resistance evolution. To do so, we used the host bacterium Pseudomonas fluorescens SBW25 and a diverse suite of coevolved viral parasites (lytic bacteriophage Φ2) with variable host ranges (defined here as the number of host genotypes that can be infected) as our experimental model organisms. Our results show that resistance evolution to coevolved phages occurred at a much lower rate than to ancestral phage (approximately 50% vs. 100%), but the host range of coevolved phages did not influence the likelihood of resistance evolution. We also show that the host range of both single parasites and populations of parasites does not affect the breadth of the resulting resistance range in a naïve host but that hosts that evolve resistance to single parasites are more likely to resist other (genetically) more closely related parasites as a correlated response. These findings have important implications for our understanding of resistance evolution in natural populations of bacteria and viruses and other host–parasite combinations with similar underlying infection genetics, as well as the development of phage therapy.     

Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata

Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.     

Parasite diversity drives rapid host dynamics and evolution of resistance in a bacteria‐phage system

Host–parasite evolutionary interactions are typically considered in a pairwise species framework. However, natural infections frequently involve multiple parasites. Altering parasite diversity alters ecological and evolutionary dynamics as parasites compete and hosts resist multiple infection. We investigated the effects of parasite diversity on host–parasite population dynamics and evolution using the pathogen Pseudomonas aeruginosa and five lytic bacteriophage parasites. To manipulate parasite diversity, bacterial populations were exposed for 24 hours to either phage monocultures or diverse communities containing up to five phages. Phage communities suppressed host populations more rapidly but also showed reduced phage density, likely due to interphage competition. The evolution of resistance allowed rapid bacterial recovery that was greater in magnitude with increases in phage diversity. We observed no difference in the extent of resistance with increased parasite diversity, but there was a profound impact on the specificity of resistance; specialized resistance evolved to monocultures through mutations in a diverse set of genes. In summary, we demonstrate that parasite diversity has rapid effects on host–parasite population dynamics and evolution by selecting for different resistance mutations and affecting the magnitude of bacterial suppression and recovery. Finally, we discuss the implications of phage diversity for their use as biological control agents.     

Effects of antagonistic coevolution on parasite‐mediated host coexistence

Parasites can promote diversity by mediating coexistence between a poorer and superior competitor, if the superior competitor is more susceptible to parasitism. However, hosts and parasites frequently undergo antagonistic coevolution. This process may result in the accumulation of pleiotropic fitness costs associated with host resistance, and could breakdown coexistence. We experimentally investigated parasite‐mediated coexistence of two genotypes of the bacterium Pseudomonas fluorescens, where one genotype underwent coevolution with a parasite (a virulent bacteriophage), whereas the other genotype was resistant to the evolving phages at all time points, but a poorer competitor. In the absence of phages, the resistant genotype was rapidly driven extinct in all populations. In the presence of the phages, the resistant genotype persisted in four of six populations and eventually reached higher frequencies than the sensitive genotype. The coevolving genotype showed a reduction in the growth rate, consistent with a cost of resistance, which may be responsible for a decline in its relative fitness. These results demonstrate that the stability of parasite‐mediated coexistence of resistant and susceptible species or genotypes is likely to be affected if parasites and susceptible hosts coevolve.     

Differences in parasite susceptibility and costs of resistance between naturally exposed and unexposed host populations

It is generally assumed that resistance to parasitism entails costs. Consequently, hosts evolving in the absence of parasites are predicted to invest less in costly resistance mechanisms than hosts consistently exposed to parasites. This prediction has, however, rarely been tested in natural populations. We studied the susceptibility of three naïve, three parasitized and one recently isolated Asellus aquaticus isopod populations to an acanthocephalan parasite. We found that parasitized populations, with the exception of the isopod population sympatric with the parasite strain used, were less susceptible to the parasite than the naïve populations. Exposed but uninfected (resistant) isopods from naïve populations, but not from parasitized populations, exhibited greater mortality than controls, implying that resistance entails survival costs primarily for naïve isopods. These results suggest that parasites can drive the evolution of host resistance in the wild, and that co‐existence with parasites may increase the cost‐effectiveness of defence mechanisms.     

Direct and correlated responses to selection in a host-parasite system: testing for the emergence of genotype specificity

Genotype x environment interactions can facilitate coexistence of locally adapted specialists. Interactions evolve if adaptation to one environment trades off with performance in others. We investigated whether evolution on one host genotype traded off with performance on others in long-term experimental populations of different genotypes of the protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. A total of nine parasite selection lines evolving on three host genotypes and the ancestral parasite were tested in a cross-infection experiment. We found that evolved parasites produced more infections than did the ancestral parasites, both on host genotypes they had evolved on (positive direct response to selection) and on genotypes they had not evolved on (positive correlated response to selection). On two host genotypes, a negative relationship between direct and correlated responses indicated pleiotropic costs of adaptation. On the third, a positive relationship suggested cost-free adaptation. Nonetheless, on all three hosts, resident parasites tended to be superior to the average nonresident parasite. Thus genotype specificity (i.e., patterns of local adaptation) may evolve without costs of adaptation, as long as direct responses to selection exceed correlated responses.     

The cost of phage resistance in a plant pathogenic bacterium is context‐dependent

Parasites are ubiquitous features of living systems and many parasites severely reduce the fecundity or longevity of their hosts. This parasite‐imposed selection on host populations should strongly favor the evolution of host resistance, but hosts typically face a trade‐off between investment in reproductive fitness and investment in defense against parasites. The magnitude of such a trade‐off is likely to be context‐dependent, and accordingly costs that are key in shaping evolution in nature may not be easily observable in an artificial environment. We set out to assess the costs of phage resistance for a plant pathogenic bacterium in its natural plant host versus in a nutrient‐rich, artificial medium. We demonstrate that mutants of Pseudomonas syringae that have evolved resistance via a single mutational step pay a substantial cost for this resistance when grown on their tomato plant hosts, but do not realize any measurable growth rate costs in nutrient‐rich media. This work demonstrates that resistance to phage can significantly alter bacterial growth within plant hosts, and therefore that phage‐mediated selection in nature is likely to be an important component of bacterial pathogenicity.     

Host manipulation by parasites in the world of dead-end predators: adaptation to enhance transmission?

Trophically transmitted parasites often alter their intermediate host's phenotype, thereby predisposing the hosts to increased predation. This is generally considered a parasite strategy evolved to enhance transmission to the next hosts. However, the adaptive value of host manipulation is not clear as it may be associated with costs, such as increased susceptibility to predators that are unsuitable next hosts for the parasites. We examined the ratio between the benefits and costs of host manipulation for transmission success of Acanthocephalus lucii (Acanthocephala), a parasite that alters the hiding behaviour and pigmentation of its isopod hosts. We experimentally compared the susceptibility of infected and uninfected isopods to predation by perch (Perca fluvialis; definitive host of the parasite) and dragonfly larvae (dead end). We found that the parasite predisposed the isopods to predation by both predators. However, the increased predation vulnerability of the infected isopods was higher towards perch. This suggests that, despite the costs due to non-host predation, host manipulation may still be advantageous for the parasite.     

Host lifespan and the evolution of resistance to multiple parasites

Hosts are typically challenged by multiple parasites, but to date theory on the evolution of resistance has mainly focused on single infections. We develop a series of models that examine the impact of multiple parasites on the evolution of resistance under the assumption that parasites coexist at the host population scale as a consequence of superinfection. In this way, we are able to explicitly examine the impact of ecological dynamics on the evolutionary outcome. We use our models to address a key question of how host lifespan affects investment in resistance to multiple parasites. We show that investment in costly resistance depends on the specificity of the immune response and on whether or not the focal parasite leads to more acute infection than the co‐circulating parasite. A key finding is that investment in resistance always increases as the immune response becomes more general independently of whether it is the focal or the co‐circulating parasite that exploits the host most aggressively. Long‐lived hosts always invest more than short‐lived hosts in both general resistance and resistance that is specific to relatively acute focal parasites. However, for specific resistance to parasites that are less acute than co‐circulating parasites it is the short‐lived hosts that are predicted to invest most. We show that these results apply whatever the mode of defence, that is whether it is through avoidance or through increased recovery, with or without acquired immunity, or through acquired immunity itself. As a whole, our results emphasize the importance of considering multiple parasites in determining optimal immune investment in eco‐evolutionary systems.     

Host manipulation as a parasite transmission strategy when manipulation is exploited by non-host predators

Trophically transmitted parasites often alter their intermediate host's phenotype, thereby predisposing hosts to increased predation. This is generally considered to be a parasite strategy evolved to enhance transmission to the next host. However, the adaptive value of host manipulation is not clear, as it may be associated with costs, such as increased susceptibility to predator species that are unsuitable next hosts for the parasites. Thus, it has been proposed that, to be adaptive, manipulation should be specific by predisposing hosts more strongly to predation by target hosts (next host in the life cycle) than to non-hosts. Here we formally evaluate this prediction, and show that manipulation does not have to be specific to be adaptive. However, when manipulation is nonspecific, it needs to effectively increase the overall predation risk of infected hosts if it is to increase the parasite transmission probability. Thus, when initial predation risk is low, even highly nonspecific manipulation strategies can be adaptive. However, when initial predation risk is high, manipulation needs to be more specific to increase parasite transmission success. Therefore, nonspecific host manipulation may evolve in nature, but the adaptive value of a certain manipulation strategy can vary among different parasite populations depending on the variation in initial predation risk.     

Relative number of generations of hosts and parasites does not influence parasite local adaptation in coevolving populations of bacteria and phages

A potential consequence of host-parasite coevolution in spatially structured populations is parasite local adaptation: local parasites perform better than foreign parasites on their local host populations. It has been suggested that the generally shorter generation times of parasites compared with their hosts contributes to parasites, rather than hosts, being locally adapted. We tested the hypothesis that relative generation times of hosts and parasites affect local adaptation of hosts and parasites, using the bacterium Pseudomonas fluorescens and a lytic phage as host and parasite, respectively. Generation times were not directly manipulated, but instead one of the coevolving partners was regularly removed and replaced with a population from an earlier time point. Thus, one partner underwent more generations than the other. Manipulations were carried out at both early and later periods of coevolutionary interactions. At early stages of coevolution, host and parasites that underwent relatively more generations displayed higher levels of resistance and infectivity, respectively. However, the relative number of generations that bacteria and phages underwent did not change the level of local adaptation relative to control populations. This is likely because generalist hosts and parasites are favoured during early stages of coevolution, preventing local adaptation. By contrast, at later stages manipulations had no effect on either average levels of resistance or infectivity, or alter the level of local adaptation relative to the controls, possibly because traits other than resistance and infectivity were under strong selection. Taken together, these data suggest that the relative generation times of hosts and parasites may not be an important determinant of local adaptation in this system.     

Adaptation of the fungal parasite Zygorhizidium planktonicum during 200 generations of growth on homogeneous and heterogeneous populations of its host, the diatom Asterionella formosa

We followed adaptation of the chytrid parasite Zygorhizidium planktonicum during 200 generations of growth on its host, the freshwater diatom Asterionella formosa, in a serial passage experiment. Evolution of parasite fitness was assessed both on a homogenous and heterogeneous host population, consisting of respectively a single new and ten different new host strains. These 10 host strains were genetically different and also varied in their initial susceptibility to the parasite. Parasite fitness increased significantly and rapidly on the new, genetically homogenous host population, but remained unaltered during 200 generations of growth on the heterogeneous host population. Enhanced parasite fitness was the result of faster and more efficient transmission, resulting in higher values of R0 (number of secondary infections). Consequently, parasites that evolved within the uniclonal host population infected significantly more of these hosts than did their ancestors. We thus provide experimental evidence for the widely held view that host genetic diversity restricts evolution of parasites and moderates their harmful effects. Genetically uniform host populations are not only at increased risk from fungal epidemics because they all share the same susceptibility, but also because new parasite strains are able to adapt quickly to new host environments and to improve their fitness.     

Within- and between-population variation for resistance of Daphnia magna to the bacterial endoparasite Pasteuria ramosa

Genetic variation among hosts for resistance to parasites is an important assumption underlying evolutionary theory of host and parasite evolution. Using the castrating bacterial parasite Pasteuria ramosa and its cladoceran host Daphnia magna, we examined both within- and between-population genetic variation for resistance. First, we tested hosts from four populations for genetic variation for resistance to three parasite isolates. Allozyme analysis revealed significant host population divergence and that genetic distance corresponds to geographic distance. Host and parasite fitness components showed strong genetic differences between parasite isolates for host population by parasite interactions and for clones within populations, whereas host population effects were significant for only a few traits. In a second experiment we tested explicitly for within-population differences in variation for resistance by challenging nine host clones from a single population with four different parasite spore doses. Strong clone and dose effects were evident. More susceptible clones also suffered higher costs once infected. The results indicate that within-population variation for resistance is high relative to between-population variation. We speculate that P. ramosa adapts to individual host clones rather than to its host population.     

Experimental evolution of field populations of Daphnia magna in response to parasite treatment

Although there is little doubt that hosts evolve to reduce parasite damage, little is known about the evolutionary time scale on which host populations may adapt under natural conditions. Here we study the effects of selection by the microsporidian parasite Octosporea bayeri on populations of Daphnia magna. In a field study, we infected replicated populations of D. magna with the parasite, leaving control populations uninfected. After two summer seasons of experimental evolution (about 15 generations), the genetic composition of infected host populations differed significantly from the control populations. Experiments revealed that hosts from the populations that had evolved with the parasite had lower mortality on exposure to parasite spores and a higher competitive ability than hosts that had evolved without the parasite. In contrast, the susceptibility of the two treatment groups to another parasite, the bacterium Pasteuria ramosa, which was not present during experimental evolution of the populations, did not differ. Fitness assays in the absence of parasites revealed a higher fitness for the control populations, but only under low population density with high resource availability. Overall, our results show that, under natural conditions, Daphnia populations are able to adapt rapidly to the prevailing conditions and that this evolutionary change is specific to the environment.     

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.     

Temporal patterns of genetic variation for resistance and infectivity in a Daphnia-microparasite system

Theoretical studies have indicated that the population genetics of host-parasite interactions may be highly dynamic. with parasites perpetually adapting to common host genotypes and hosts evolving resistance to common parasite genotypes. The present study examined temporal variation in resistance of hosts and infectivity of parasites within three populations of Daphnia magna infected with the sterilizing bacterium Pasteuria ramosa. Parasite isolates and host clones were collected in each of two years (1997, 1998) from one population; in two other populations, hosts were collected from both years, but parasites from only the first year. We then performed infection experiments (separately for each population) that exposed hosts to parasites from the same year or made combinations involving hosts and parasites from different years. In two populations, patterns were consistent with the evolution of host resistance: either infectivity or the speed with which parasites sterilized hosts declined from 1997 to 1998. In another population, infectivity, virulence, and parasite spore production did not vary among host-year or parasite-year. For this population, we also detected strong within-population genetic variation for resistance. Thus, in this case, genetic variability for fitness-related traits apparently did not translate into evolutionary change. We discuss a number of reasons why genetic change may not occur as expected in parasite-host systems, including negative correlations between resistance and other traits, gene flow, or that the dynamic process itself may obscure the detection of gene frequency changes.     

Variation in costs of parasite resistance among natural host populations

Organisms that can resist parasitic infection often have lower fitness in the absence of parasites. These costs of resistance can mediate host evolution during parasite epidemics. For example, large epidemics will select for increased host resistance. In contrast, small epidemics (or no disease) can select for increased host susceptibility when costly resistance allows more susceptible hosts to outcompete their resistant counterparts. Despite their importance for evolution in host populations, costs of resistance (which are also known as resistance trade‐offs) have mainly been examined in laboratory‐based host–parasite systems. Very few examples come from field‐collected hosts. Furthermore, little is known about how resistance trade‐offs vary across natural populations. We addressed these gaps using the freshwater crustacean Daphnia dentifera and its natural yeast parasite, Metschnikowia bicuspidata. We found a cost of resistance in two of the five populations we studied – those with the most genetic variation in resistance and the smallest epidemics in the previous year. However, yeast epidemics in the current year did not alter slopes of these trade‐offs before and after epidemics. In contrast, the no‐cost populations showed little variation in resistance, possibly because large yeast epidemics eroded that variation in the previous year. Consequently, our results demonstrate variation in costs of resistance in wild host populations. This variation has important implications for host evolution during epidemics in nature.     

ON THE EVOLUTION OF SEXUAL REPRODUCTION IN HOSTS COEVOLVING WITH MULTIPLE PARASITES

Host–parasite coevolution has been studied extensively in the context of the evolution of sex. Although hosts typically coevolve with several parasites, most studies considered one‐host/one‐parasite interactions. Here, we study population‐genetic models in which hosts interact with two parasites. We find that host/multiple‐parasite models differ nontrivially from host/single‐parasite models. Selection for sex resulting from interactions with a single parasite is often outweighed by detrimental effects due to the interaction between parasites if coinfection affects the host more severely than expected based on single infections, and/or if double infections are more common than expected based on single infections. The resulting selection against sex is caused by strong linkage‐disequilibria of constant sign that arise between host loci interacting with different parasites. In contrast, if coinfection affects hosts less severely than expected and double infections are less common than expected, selection for sex due to interactions with individual parasites can now be reinforced by additional rapid linkage‐disequilibrium oscillations with changing sign. Thus, our findings indicate that the presence of an additional parasite can strongly affect the evolution of sex in ways that cannot be predicted from single‐parasite models, and that thus host/multiparasite models are an important extension of the Red Queen Hypothesis.     

Adaptation to abiotic conditions drives local adaptation in bacteria and viruses coevolving in heterogeneous environments

Parasite local adaptation, the greater performance of parasites on their local compared with foreign hosts, has important consequences for the maintenance of diversity and epidemiology. While the abiotic environment may significantly affect local adaptation, most studies to date have failed either to incorporate the effects of the abiotic environment, or to separate them from those of the biotic environment. Here, we tease apart biotic and abiotic components of local adaptation using the bacterium Pseudomonas fluorescens and its viral parasite bacteriophage Φ2. We coevolved replicate populations of bacteria and phages at three different temperatures, and determined their performance against coevolutionary partners from the same and different temperatures. Crucially, we measured performance at different assay temperatures, which allowed us to disentangle adaptation to biotic and abiotic habitat components. Our results show that bacteria and phages are more resistant and infectious, respectively, at the temperature at which they previously coevolved, confirming that local adaptation to abiotic conditions can play a crucial role in determining parasite infectivity and host resistance. Our work underlines the need to assess host–parasite interactions across multiple relevant abiotic environments, and suggests that microbial adaption to local temperatures can create ecological barriers to dispersal across temperature gradients.     

THE ORIGIN OF SPECIFICITY BY MEANS OF NATURAL SELECTION: EVOLVED AND NONHOST RESISTANCE IN HOST–PATHOGEN INTERACTIONS

Most species seem to be completely resistant to most pathogens and parasites. This resistance has been called “nonhost resistance” because it is exhibited by species that are considered not to be part of the normal host range of the pathogen. A conceptual model is presented suggesting that failure of infection on nonhosts may be an incidental by‐product of pathogen evolution leading to specialization on their source hosts. This model is contrasted with resistance that results from hosts evolving to resist challenge by their pathogens, either as a result of coevolution with a persistent pathogen or as the result of one‐sided evolution by the host against pathogens that are not self‐sustaining on those hosts. Distinguishing evolved from nonevolved resistance leads to contrasting predictions regarding the relationship between resistance and genetic distance. An analysis of cross‐inoculation experiments suggests that the resistance is often the product of pathogen specialization. Understanding the contrasting evolutionary origins of resistance is critical for studies on the genetics and evolution of host–pathogen interactions in human, agricultural, and natural populations. Research on human infectious disease using animal models may often study resistances that have quite contrasting evolutionary origins, and therefore very different underlying genetic mechanisms.