Cooperation,virulence and siderophore production in bacterial parasites

Kin selection theory predicts that the damage to a host resulting from parasite infection (parasite virulence) will be negatively correlated to the relatedness between parasites within the host. This occurs because a lower relatedness leads to greater competition for host resources, which favours rapid growth to achieve greater relative success within the host, and that higher parasite growth rate leads to higher virulence. We show that a biological feature of bacterial infections can lead to the opposite prediction: a positive correlation between relatedness and virulence. This occurs because a high relatedness can favour greater (cooperative) production of molecules that scavenge iron (siderophores), which results in higher growth rates and virulence. More generally, the same underlying idea can predict a positive relationship between relatedness and virulence in any case where parasites can cooperate to increase their growth rate; other examples include immune suppression and the production of biofilms to aid colonization.     

Virulence evolution via host exploitation and toxin production in spore-producing pathogens

Many pathogens produce resilient free-living propagules that allow their dissemination in the absence of direct contact between susceptible and infected hosts. One might expect pathogens capable of producing such long-lived propagules to evolve high levels of virulence because their reproductive success is de-coupled from the survival of their host. Despite some comparative data supporting this prediction, theory has questioned its general validity. I present theoretical results that incorporate two transmission routes neglected by previous theory: death-mediated propagule production and direct host-host transmission. This theory predicts that spore-producing pathogens should evolve high levels of virulence under quite broad conditions. Moreover, a novel prediction of this theory is that the production of propagules can generate selection for the evolution of pathogen characteristics such as toxins whose sole function is to kill the host. This latter result reveals an unanticipated mechanism through which virulence is expected to evolve in spore-producing pathogens.     

Decomposing propagule pressure: the effects of propagule size and propagule frequency on invasion success

Propagule pressure quantifies the inflow of individuals to a location and appears to be a key driver of invasion success. It is often defined as the average number of individuals introduced per time unit, or equivalently as the product of the average number of individuals introduced per introduction event (propagule size) and the frequency of introduction events (propagule frequency). Here we study how the influence of propagule size, frequency, and their product depends on the underlying ecological conditions. While previous studies have focused on introductions under environmental heterogeneity or a strong Allee effect, we examine a range of ecological scenarios that differ in the type of density dependence and in the sign of per capita growth rate. Our results indicate that the relative influence of propagule size and frequency depends mainly on the sign of per capita growth rate. Given a certain average number of individuals introduced per time unit, a high propagule frequency accelerates invasions under ecological scenarios with positive average per capita growth rate throughout the invasion process (‘easy’ scenarios). If per capita growth rate is negative throughout the invasion process (‘difficult’ scenarios) or if there is both an easy and a difficult stage (‘mixed scenarios’), a high propagule size leads to a faster invasion than a high propagule frequency. To explain this finding, we argue that for a fixed value of the product of propagule size and frequency, an increase in propagule size leads to an increase in demographic variance, which promotes invasion success in difficult and mixed but not in easy scenarios. However, we also show that in many of these cases, the product of propagule size and frequency still correlates more strongly with invasion success than either of the single components. Finally, we illustrate our approach with empirical examples from the literature.     

Proteome of Aedes aegypti in response to infection and coinfection with microsporidian parasites

Hosts are frequently infected with more than one parasite or pathogen at any one time, but little is known as to how they respond to multiple immune challenges compared to those involving single infections. We investigated the proteome of Aedes aegypti larvae following infection with either Edhazardia aedis or Vavraia culicis, and coinfections involving both. They are both obligate intracellular parasites belonging to the phylum microsporidia and infect natural populations of Ae. aegypti. The results found some proteins only showing modified abundance in response to infections involving E. aedis, while others were only differentially abundant when infections involved V. culicis. Some proteins only responded with modified abundance to the coinfection condition, while others were differentially abundant in response to all three types of infection. As time since infection increased, the response to each of the single parasite infections diverged, while the response to the E. aedis and coinfection treatments converged. Some of the proteins differentially abundant in response to infection were identified. They included two vacuolar ATPases, proteins known to have a role in determining the infection success of intracellular parasites. This result suggests microsporidia could influence the infection success of other intracellular pathogens infecting vector species of mosquito, including viruses, Plasmodium and Wolbachia.     

The evolution of virulence in vector-borne and directly transmitted parasites

Ewald (1994) has suggested that vector-borne parasites are expected to evolve a higher level of host exploitation than directly transmitted parasites, and this should thereby result in them being more virulent. Indeed, some data do conform to this general pattern. Nevertheless, his hypothesis has generated some debate about the extent to which it is valid. I explore this issue quantitatively within the framework of mathematical epidemiology. In particular, I present a dynamic optimization model for the evolution of parasite replication strategies that explicitly explores the validity of this hypothesis. A few different model assumptions are explored and it is found that Ewald's hypothesis has only qualified support as a general explanation for why vector-borne parasites are more virulent than those that are directly transmitted. I conclude by suggesting that an alternative explanation might lie in differences in inoculum size between these two types of transmission.     

In situ development of the foliicolous lichen Phyllophiale (Trichotheliaceae) from propagule germination to propagule production

The vegetative cycle of the foliicolous lichen Phyllophiale, from propagule germination to propagule production, was studied by light microscope observation of thalli colonizing plastic cover slips placed within a lowland tropical forest. Discoid propagules germinated by growth of radially arranged fungal cells and developed directly into lichen thalli. The young lichen comprised a single disc of closely branched, radiating filaments of the algal symbiont Phycopeltis, covered by a network of fungal hyphae extending onto the substrate as a prothallus. The prothallic hyphae incorporated additional Phycopeltis thalli encountered on the substrate. The phycobiont formed a single layer, with individual algal thalli clearly distinguishable within the lichen. Radial growth ceased at points of contact between adjacent phycobiont thalli. The visible shape of the crustose lichen thallus corresponded to the perimeter of the phycobiont thalli within. Propagules were initiated at points corresponding to the margins of the phycobiont thalli, by vertical reorientation of horizontal algal filaments surrounded by fungal hyphae. The lichenized alga produced intercalary gametangia. Degeneration of propagules unsuccessful in lichen establishment sometimes resulted in free growth of the phycobiont. The alga generally maintained its shape, growth pattern, and reproductive independence within the lichen, while also participating in the formation of unique symbiotic propagules.     

Evolution and virulence of primate lentiviruses

While the AIDS epidemic caused by human immunodeficiency viruses (HIV) has resulted in the death of over 20 million people worldwide, simian immunodeficiency virus (SIV) infection, found in numerous African primate species, does not induce disease symptoms. The factors accounting for this difference between humans and natural host of SIV remain poorly understood. The entangled nature of the host/virus relationship could be the answer, rather than independent virus or host factors. Such a relationship is as a consequence of host/virus adaptation which has evolved over long periods in naturally infected primate species.     

Host plant species affects virulence in monarch butterfly parasites

1. Studies have considered how intrinsic host and parasite properties determine parasite virulence, but have largely ignored the role of extrinsic ecological factors in its expression. 2. We studied how parasite genotype and host plant species interact to determine virulence of the protozoan parasite Ophryocystis elektroscirrha (McLaughlin & Myers 1970) in the monarch butterfly Danaus plexippus L. We infected monarch larvae with one of four parasite genotypes and reared them on two milkweed species that differed in their levels of cardenolides: toxic chemicals involved in predator defence. 3. Parasite infection, replication and virulence were affected strongly by host plant species. While uninfected monarchs lived equally long on both plant species, infected monarchs suffered a greater reduction in their life spans (55% vs. 30%) on the low-cardenolide vs. the high-cardenolide host plant. These life span differences resulted from different levels of parasite replication in monarchs reared on the two plant species. 4. The virulence rank order of parasite genotypes was unaffected by host plant species, suggesting that host plant species affected parasite genotypes similarly, rather than through complex plant species-parasite genotype interactions. 5. Our results demonstrate that host ecology importantly affects parasite virulence, with implications for host-parasite dynamics in natural populations.     

Shared epigenetic mechanisms control virulence factors in protozoan parasites

Protozoan pathogens have evolved countermeasures to avoid immune clearance and prolong the period of infection in their vertebrate hosts. The type and degree of immune escape strategies depends on the in vivo 'lifestyle' the pathogen has adopted. Here we describe how parasites use different strategies to coordinate their expression of phenotypic variation, which is used in many cases to fool the immune system, or to successfully invade new host cells. Recent insights using modern molecular biology techniques show that this is achieved via a coordinated manner of action of different epigenetic factors such as histone marks, subnuclear localization, or novel unknown mechanism(s). This emerging field may have an enormous impact on disease therapy.     

Evolution of prokaryotic and eukaryotic virulence effectors

Coevolutionary interactions between plants and their bacterial and eukaryotic pathogens are mediated by virulence effectors. These effectors face the daunting challenge of carrying out virulence functions, while also potentially exposing the pathogen to host defense systems. Very strong selective pressures are imposed by these competing roles, and the subsequent genetic changes leave their footprints in the extant allelic variation. This review examines the evolutionary processes that drive pathogen-host interactions as revealed by the genetic signatures left in virulence effectors, and speculate on the different pressures imposed on bacterial versus eukaryotic pathogens. We find numerous instances of positive selection for new allelic forms, and diversifying selection for genetic variability, which results in altered host-pathogen interactions. We also describe how the genetic structure of both bacterial and eukaryotic virulence effectors may contribute to their rapid generation and turnover.     

Differences in accumulation and virulence determine the outcome of competition during Tobacco etch virus coinfection

Understanding the evolution of virulence for RNA viruses is essential for developing appropriate control strategies. Although it has been usually assumed that virulence is a consequence of within-host replication of the parasite, viral strains may be highly virulent without experiencing large accumulation as a consequence of immunopathological host responses. Using two strains of Tobacco etch potyvirus (TEV) that show a negative relationship between virulence and accumulation rate, we first explored the evolution of virulence and fitness traits during simple and mixed infections. Short-term evolution experiments initiated with each strain independently confirmed the genetic and evolutionary stability of virulence and viral load, although infectivity significantly increased for both strains. Second, competition experiments between hypo- and hypervirulent TEV strains have shown that the outcome of competition is driven by differences in replication rate. A simple mathematical model has been developed to analyze the dynamics of these two strains during coinfection. The model qualitatively reproduced the experimental results using biologically meaningful parameters. Further analyses of the model also revealed a wide parametric region in which a low-fitness but hypovirulent virus can still outcompete a high-fitness but hypervirulent one. These results provide additional support to the observation that virulence and within-host replication may not necessarily be strongly tied in plant RNA viruses.     

Low migration decreases interference competition among parasites and increases virulence

Competition among different parasite genotypes within a host is predicted to affect virulence. The direction of this effect, however, depends critically on the mechanisms that parasites use to compete or to cooperate with each other. One mechanism that bacteria use to compete with each other is via the production of bacteria-killing toxins, called bacteriocins. This warfare among parasites within a host is predicted to reduce the rate of host exploitation, resulting in lower virulence. By contrast, if parasites within a host are highly related, there could be a reduction in within-host conflict, increasing virulence. We examined this idea by allowing an insect-parasitic nematode (Steinernema carpocapsae) and its symbiotic bacteria (Xenorhabdus nematophila) to evolve for 20 passages under two different migration treatments (low and high). We found that host mortality rates were higher in the low-migration treatment when compared with the high-migration treatment. In addition, bacteria isolated from the same insect host inhibited each other's growth, but only in the high-migration treatment. These results show that population structure and interactions among parasites within hosts can be critical to understanding virulence.     

Evolution of microbial virulence: the benefits of stress

Although genome sequencing of microbial pathogens has shed light on the evolution of virulence, the drivers of the gain and loss of genes and of pathogenicity islands (gene clusters), which contribute to the emergence of new disease outbreaks, are unclear. Recent experiments with the bean pathogen Pseudomonas syringae pv. phaseolicola illustrate how exposure to resistance mechanisms acts as the driving force for genome reorganization. Here we argue that the antimicrobial conditions generated by host defences can accelerate the generation of genome rearrangements that provide selective advantages to the invading microbe. Similar exposure to environmental stress outside the host could also drive the horizontal gene transfer that has led to the evolution of pathogenicity towards both animals and plants.     

Evolution of early male-killing in horizontally transmitted parasites

Early male-killing (MK) bacteria are vertically transmitted reproductive parasites which kill male offspring that inherit them. Whereas their incidence is well documented, characteristics allowing originally non-MK bacteria to gradually evolve MK ability remain unclear. We show that horizontal transmission is a mechanism enabling vertically transmitted bacteria to evolve fully efficient MK under a wide range of host and parasite characteristics, especially when the efficacy of vertical transmission is high. We also show that an almost 100% vertically transmitted and 100% effective male-killer may evolve from a purely horizontally transmitted non-MK ancestor, and that a 100% efficient male-killer can form a stable coexistence only with a non-MK bacterial strain. Our findings are in line with the empirical evidence on current MK bacteria, explain their high efficacy in killing infected male embryos and their variability within and across insect taxa, and suggest that they may have evolved independently in phylogenetically distinct species.     

Evolution of resistance and virulence in plant-herbivore and plant-pathogen interactions

Herbivores and pathogens often attack or infect the same plant parts, and the same plant traits can affect the likelihood and degree of damage. Research on plant-herbivore and plant-pathogen interactions in natural systems have, however, proceeded largely independently of each other. Our understanding of both types of plant-enemy interaction would be enhanced by greater exposure of researchers to developments in both disciplines and by more studies of interactions between pathogen and herbivore species associated with the same hosts.     

Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control

Standard virulence evolution theory assumes that virulence factors are maintained because they aid parasitic exploitation, increasing growth within and/or transmission between hosts. An increasing number of studies now demonstrate that many opportunistic pathogens (OPs) do not conform to these assumptions, with virulence factors maintained instead because of advantages in non-parasitic contexts. Here we review virulence evolution theory in the context of OPs and highlight the importance of incorporating environments outside a focal virulence site. We illustrate that virulence selection is constrained by correlations between these external and focal settings and pinpoint drivers of key environmental correlations, with a focus on generalist strategies and phenotypic plasticity. We end with a summary of key theoretical and empirical challenges to be met for a fuller understanding of OPs.