Arrested larval development in cattle nematodes

Most economically important cattle nematodes are able to arrest their larval development within the host - entering a period of dormancy or hypobiosis. Arrested larvae have a low death rate, and large numbers can accumulate in infected cattle during the grazing season. Because of this, outbreaks of disease caused by such nematodes can occur at times when recent infection with the parasites could not have occurred, for example during winter in temperature northern climates when cattle are normally housed. The capacity to arrest is a heritable trait. It is seen as an adaptation by the parasite to avoid further development to its free-living stages during times when the climate is unsuitable for free-living survival. But levels of arrestment can vary markedly in different regions, in different cattle, and under different management regimes. Climatic factors, previous conditioning, host immune status, and farm management all seem to affect arrestment levels. In this article, James Armour and Mary Duncan review the biological basis of the phenomenon, and discuss the apparently conflicting views on how it is controlled.     

Thermoregulation in the life cycle of nematodes

An unanswered question in the biology of many parasites is the mechanism by which environmental (or external) and intrinsic signals are integrated to determine the switch from one developmental stage to the next. This is particularly pertinent for nematode parasites, many of which have a free-living stage in the environment prior to infection of the mammalian host, or for parasites such as filarial nematodes, which utilise an insect vector for transmission. The environmental changes experienced by a parasite upon infection of a mammalian host are extremely complex and poorly understood. However, the ability of a parasite to sense its new environment must be intrinsically linked to its developmental programme, as progression of the life cycle is dependent upon the infection event. In this review, the relationship between temperature and development in filarial nematodes and in the free-living species Caenorhabditis elegans is summarised, with a focus on the role of heat shock factor and heat shock protein 90 in the nematode life cycle.     

Identification of DnaJ-like chaperone in Clostridium botulinum type A

Clostridium botulinum type A cells, when challenged to elevated temperature (45°C), increased the expression of at least nine heat shock proteins (HSPs). Simultaneously with the induction of HSPs, changes in the synthesis rates of other cellular proteins were observed. A 40-kDa stress protein was induced and its synthesis rate was enhanced when the cells were shifted to 45°C. Using heterologous antibodies raised against E. coli DnaJ heat shock proteins, the 40-kDa stress protein of C. botulinum type A has been identified as a DnaJ-like chaperone. The DnaJ chaperone might be involved in translocation of the neurotoxin and other cellular proteins across the cell membrane, repair of damaged proteins, and organism survival inside the host. This is the first report of the existence of a DnaJ-like chaperone in this organism.     

Pollution and parasitism in the aquatic environment

The studies of aquatic parasitology and of aquatic pollution effects both have experienced increasing interest during the recent fifteen years. Although considerable effort has been spent on studying the role of pollution as a cause or a trigger of anomalies, tumors and infectious diseases in aquatic organisms, the interactions between pollution and parasitism have been largely neglected by scientists.Pollution and other man-made alterations of the aquatic environment may affect a parasite community directly by acting on free-living parasite stages or on ectoparasites, or indirectly by acting on the intermediate or the definitive host population. Certain pollution conditions favour the propagation of parasites by excluding their natural predators, by reducing the resistance of their hosts or by providing improved living conditions for their intermediate hosts. In a number of experimental studies parasitized organisms have been shown to suffer from greater mortalities when exposed to high temperature, to low oxygen stress or to high levels of dissolved heavy metal salts, when compared to nonparasitized control animals. Unfortunately, field studies on synergistic effects of pollution and parasites on host populations are still scarce and seldom offer more than qualitative observations and theoretical evaluations.The complexity of the pollution-parasite-host system complicates the use of parasites as indicators of pollution effects. However, experience from aquaculture practice teaches that a number of (mostly ecto-) parasites are more susceptible to certain chemicals (used as parasiticides) and to artificial alterations of salinity, temperature or oxygen content of the water than their hosts. Accordingly, it is postulated that during future studies the composition of ectoparasitic faunas of aquatic organisms might turn out to become a useful and quickly reacting indicator for effects of certain pollution conditions, such as anthropogene oxygen deficiency, salt introduction from salines into freshwater ecosystems, and introduction of certain heavy metal salts.     

Host-specificity of monogenean (platyhelminth) parasites: a role for anterior adhesive areas?

Monogeneans (flatworms) are among the most host-specific of parasites in general and may be the most host-specific of all fish parasites. Specificity, in terms of a restricted spatial distribution within an environment, is not unique to parasites and is displayed by some fungi, insects, birds, symbionts and pelagic larvae of free-living marine invertebrates. The nature of cues, how "habitats" are recognised and how interactions between partners are mediated and maintained is of interest across these diverse "associations". We review some experiments that demonstrate important factors that contribute to host-specificity at the level of infective stages (larvae of oviparous monogeneans; juveniles of viviparous gyrodactylids) and adult parasites. Recent research on immune responses by fish to monogenean infections is considered. We emphasise the critical importance of host epidermis to the Monogenea. Monogeneans live on host epidermis, they live in its products (e.g. mucus), monopisthocotyleans feed on it, some of its products are "attractants" and it may be an inhospitable surface because of its immunological activity. We focus attention on fish but reference is made to amphibian hosts. We develop the concept for a potential role in host-specificity by the anterior adhesive areas, either the specialised tegument and/or anterior secretions produced by monogeneans for temporary but firm attachment during locomotion on host epithelial surfaces. Initial contact between the anterior adhesive areas of infective stages and host epidermis may serve two important purposes. (1) Appropriate sense organs or receptors on the parasite interact with a specific chemical or chemicals or with surface structures on host epidermis. (2) A specific but instant recognition or reaction occurs between component(s) of host mucus and the adhesive(s) secreted by monogeneans. The chemical composition of fish skin is known to be species-specific and our preliminary analysis of the chemistry of some monogenean adhesives indicates they are novel proteins that display some differences between parasite families and species.     

Genome-wide identification of molecular mimicry candidates in parasites

Among the many strategies employed by parasites for immune evasion and host manipulation, one of the most fascinating is molecular mimicry. With genome sequences available for host and parasite, mimicry of linear amino acid epitopes can be investigated by comparative genomics. Here we developed an in silico pipeline for genome-wide identification of molecular mimicry candidate proteins or epitopes. The predicted proteome of a given parasite was broken down into overlapping fragments, each of which was screened for close hits in the human proteome. Control searches were carried out against unrelated, free-living eukaryotes to eliminate the generally conserved proteins, and with randomized versions of the parasite proteins to get an estimate of statistical significance. This simple but computation-intensive approach yielded interesting candidates from human-pathogenic parasites. From Plasmodium falciparum, it returned a 14 amino acid motif in several of the PfEMP1 variants identical to part of the heparin-binding domain in the immunosuppressive serum protein vitronectin. And in Brugia malayi, fragments were detected that matched to periphilin-1, a protein of cell-cell junctions involved in barrier formation. All the results are publicly available by means of mimicDB, a searchable online database for molecular mimicry candidates from pathogens. To our knowledge, this is the first genome-wide survey for molecular mimicry proteins in parasites. The strategy can be adopted to any pair of host and pathogen, once appropriate negative control organisms are chosen. MimicDB provides a host of new starting points to gain insights into the molecular nature of host-pathogen interactions.     

The role of small heat shock proteins in parasites

The natural life cycle of many protozoan and helminth parasites involves exposure to several hostile environmental conditions. Under these circumstances, the parasites arouse a cellular stress response that involves the expression of heat shock proteins (HSPs). Small HSPs (sHSPs) constitute one of the main families of HSPs. The sHSPs are very divergent at the sequence level, but their secondary and tertiary structures are conserved and some of its members are related to α-crystallin from vertebrates. They are involved in a variety of cellular processes. As other HSPs, the sHSPs act as molecular chaperones; however, they have shown other activities apparently not related to chaperone action. In this review, the diverse activities of sHSPs in the major genera of protozoan and helminth parasites are described. These include stress response, development, and immune response, among others. In addition, an analysis comparing the sequences of sHSPs from some parasites using a distance analysis is presented. Because many parasites face hostile conditions through its life cycles the study of HSPs, including sHSPs, is fundamental.     

IMMUNE EVASION AND THE EVOLUTION OF MOLECULAR MIMICRY IN PARASITES

Parasites that are molecular mimics express proteins which resemble host proteins. This resemblance facilitates immune evasion because the immune molecules with the specificity to react with the parasite also cross‐react with the host's own proteins, and these lymphocytes are rare. Given this advantage, why are not most parasites molecular mimics? Here we explore potential factors that can select against molecular mimicry in parasites and thereby limit its occurrence. We consider two hypotheses: (1) molecular mimics are more likely to induce autoimmunity in their hosts, and hosts with autoimmunity generate fewer new infections (the “costly autoimmunity hypothesis”); and (2) molecular mimicry compromises protein functioning, lowering the within‐host replication rate and leading to fewer new infections (the “mimicry trade‐off hypothesis”). Our analysis shows that although both hypotheses may select against molecular mimicry in parasites, unique hallmarks of protein expression identify whether selection is due to the costly autoimmunity hypothesis or the mimicry trade‐off hypothesis. We show that understanding the relevant selective forces is necessary to predict how different medical interventions will affect the proportion of hosts that experience the different infection types, and that if parasite evolution is ignored, interventions aimed at reducing infection‐induced autoimmunity may ultimately fail.     

The synergistic effect of hyperthermia and ethanol on changing gene expression of mouse lymphocytes

Cultured mouse lymphocytes respond to a brief incubation at an elevated temperature (41-43 degrees C) with the new and (or) enhanced synthesis of a select group of polypeptides (known as heat-shock proteins, HSPs) having relative molecular masses of 110, 100, 90, 70, and 65 kilodaltons (kDa). Expression of these HSPs is dependent on new RNA synthesis. Because the synthesis of any particular HSP is dependent on the temperature and the length of time cells remain at a particular elevated temperature, synthesis of each HSP is not necessarily coordinated with the synthesis of the other HSPs. Cultured mouse lymphocytes treated with arsenite or ethanol exhibit new and (or) enhanced synthesis of HSPs with molecular masses of 110, 90, 70, and 65 kDa but do not exhibit enhanced synthesis of the 100-kDa HSP. Short-term concurrent exposure of mouse lymphocytes to an elevated temperature and a level of ethanol, which individually do not induce detectable HSP synthesis, results in the pronounced synthesis of HSPs similar to those seen following exposure to higher levels of either stress applied separately. Thus, in this study we demonstrate that hyperthermia and ethanol stress can act synergistically to affect a dramatic change in the gene expression of mouse lymphocytes.     

Fixed behaviours and migration in parasitic flatworms

This paper considers how fixed behaviours may play a role in post-larval migrations of Entobdella soleae. A general argument is that a shift away from the paradigm of orientation is required to elucidate the mechanisms that parasites use to navigate on the surface of their hosts. Some migrations may rely on fixed behaviours (genetically programmed stereotyped behaviours) that often evolve under predictable environmental conditions with reliable signals. In turbulent and stochastic free-living environments, homeostatic hosts present very predictable topological substrates and physico-chemical characteristics to their parasites. Over the course of evolution on these predictable host substrates, adaptive behaviours in the parasites can become fixed. Examples of endoparasite migration behaviour, particularly that of the common liver fluke, Fasciola hepatica, will be used to develop an approach based on the perceptual worlds of migrating parasites. An important conclusion is that multi-disciplinary approaches, firmly rooted in an understanding of each parasite's natural history, are requisite to successful interpretation of migration behaviours on the host.     

Do Fleas Affect Energy Expenditure of Their Free-Living Hosts?

Background

Parasites can cause energetically costly behavioural and immunological responses which potentially can reduce host fitness. However, although most laboratory studies indicate that the metabolic rate of the host increases with parasite infestation, this has never been shown in free-living host populations. In fact, studies thus far have shown no effect of parasitism on field metabolic rate (FMR).

Methodology and Results

We tested the effect of parasites on the energy expenditure of a host by measuring FMR using doubly-labelled water in free-living Baluchistan gerbils (Gerbillus nanus) infested by naturally occurring fleas during winter, spring and summer. We showed for the first time that FMR of free-living G. nanus was significantly and positively correlated with parasite load in spring when parasite load was highest; this relationship approached significance in summer when parasite load was lowest but was insignificant in winter. Among seasons, winter FMRs were highest and summer FMRs were lowest in G. nanus.

Discussion

The lack of parasite effect on FMR in winter could be related to the fact that FMR rates were highest among seasons. In this season, thermoregulatory costs are high which may indicate that less energy could be allocated to defend against parasites or to compensate for other costly activities. The question about the cost of parasitism in nature is now one of the major themes in ecological physiology. Our study supports the hypothesis that parasites can elevate FMR of their hosts, at least under certain conditions. However, the effect is complex and factors such as season and parasite load are involved.     

Effects of host condition on susceptibility to infection, parasite developmental rate, and parasite transmission in a snail-trematode interaction

Whether or not organisms become infected by parasites is likely to be a complex interplay between host and parasite genotypes, as well as the physiological condition of both species. Details of this interplay are very important because physiology‐driven susceptibility has the potential to confound genetic coevolutionary responses. Here we concentrate on how physiological aspects of infection may interfere with genetic‐based infectivity in a snail–trematode (Potamopyrgus antipodarum/Microphallus sp.) interaction by asking: (1) how does host condition affect susceptibility to infection? and (2) how does host condition affect the survival of infected individuals? We manipulated host condition by experimentally varying resources. Contrary to our expectation, host condition did not affect susceptibility to infection, suggesting that genetics are more important than physiology in this regard. However, hosts in poor condition had higher parasite‐induced mortality than hosts in good condition. Taken together, these results suggest that coevolutionary interactions with parasites may depend on host condition, not by altering susceptibility, but rather by affecting the likelihood of parasite transmission.     

Parasites reduce food web robustness because they are sensitive to secondary extinction as illustrated by an invasive estuarine snail

A robust food web is one in which few secondary extinctions occur after removing species. We investigated how parasites affected the robustness of the Carpinteria Salt Marsh food web by conducting random species removals and a hypothetical, but plausible, species invasion. Parasites were much more likely than free-living species to suffer secondary extinctions following the removal of a free-living species from the food web. For this reason, the food web was less robust with the inclusion of parasites. Removal of the horn snail, Cerithidea californica, resulted in a disproportionate number of secondary parasite extinctions. The exotic Japanese mud snail, Batillaria attramentaria, is the ecological analogue of the native California horn snail and can completely replace it following invasion. Owing to the similarities between the two snail species, the invasion had no effect on predator–prey interactions. However, because the native snail is host for 17 host-specific parasites, and the invader is host to only one, comparison of a food web that includes parasites showed significant effects of invasion on the native community. The hypothetical invasion also significantly reduced the connectance of the web because the loss of 17 native trematode species eliminated many links.     

Migration highways and migration barriers created by host–parasite interactions

Co‐evolving parasites may play a key role in host migration and population structure. Using co‐evolving bacteria and viruses, we test general hypotheses as to how co‐evolving parasites affect the success of passive host migration between habitats that can support different intensities of host–parasite interactions. First, we show that parasites aid migration from areas of intense to weak co‐evolutionary interactions and impede migration in the opposite direction, as a result of intraspecific apparent competition mediated via parasites. Second, when habitats show qualitative difference such that some environments support parasite persistence while others do not, different population regulation forces (either parasitism or competitive exclusion) will reduce the success of migration in both directions. Our study shows that co‐evolution with parasites can predictably homogenises or isolates host populations, depending on heterogeneity of abiotic conditions, with the second scenario constituting a novel type of ‘isolation by adaptation’.     

Heat shock proteins: essential proteins for apoptosis regulation

Many different external and intrinsic apoptotic stimuli induce the accumulation in the cells of a set of proteins known as stress or heat shock proteins (HSPs). HSPs are conserved proteins present in both prokaryotes and eukaryotes. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and by preventing their aggregation. HSPs have a protective function, that is they allow the cells to survive to otherwise lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several of these proteins have demonstrated to directly interact with components of the cell signalling pathways, for example those of the tightly regulated caspase-dependent programmed cell death machinery, upstream, downstream and at the mitochondrial level. HSPs can also affect caspase-independent apoptosis-like process by interacting with apoptogenic factors such as apoptosis-inducing factor (AIF) or by acting at the lysosome level. This review will describe the different key apoptotic proteins interacting with HSPs and the consequences of these interactions in cell survival, proliferation and apoptotic processes. Our purpose will be illustrated by emerging strategies in targeting these protective proteins to treat haematological malignancies.     

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.     

HOST IMMUNE STATUS DETERMINES SEXUALITY IN A PARASITIC NEMATODE

We examine the hypothesis that sexual reproduction by parasites is an adaptation to counter the somatic evolution of vertebrate immune responses. This is analogous to the idea that antagonistic coevolution between hosts and their parasites maintains sexual reproduction in host populations. Strongyloides ratti is a parasitic nematode of rats. It can have a direct life cycle, with clonal larvae of the wholly parthenogenetic parasites becoming infective, or an indirect life cycle, with clonal larvae developing into free-living dioecious adults. These free-living adults produce infective larvae by conventional meiosis and syngamy. The occurrence of the sexual cycle is determined by both environmental and genetic factors. By experimentally manipulating host immune status using hypothymic mutants, corticosteroids, whole-body γ-irradiation and previous exposure to S. ratti, we show that larvae from hosts that have acquired immune protection are more likely to develop into sexual adults. This effect is independent of the method of manipulation, larval density, and the number of days postinfection. This immune-determined sexuality is consistent with the idea that sexual reproduction by parasites is adaptive in the face of specific immunity, an idea which, if true, has clinical and epidemiological consequences.     

Biodiversity loss decreases parasite diversity: theory and patterns

Past models have suggested host-parasite coextinction could lead to linear, or concave down relationships between free-living species richness and parasite richness. I explored several models for the relationship between parasite richness and biodiversity loss. Life cycle complexity, low generality of parasites and sensitivity of hosts reduced the robustness of parasite species to the loss of free-living species diversity. Food-web complexity and the ordering of extinctions altered these relationships in unpredictable ways. Each disassembly of a food web resulted in a unique relationship between parasite richness and the richness of free-living species, because the extinction trajectory of parasites was sensitive to the order of extinctions of free-living species. However, the average of many disassemblies tended to approximate an analytical model. Parasites of specialist hosts and hosts higher on food chains were more likely to go extinct in food-web models. Furthermore, correlated extinctions between hosts and parasites (e.g. if parasites share a host with a specialist predator) led to steeper declines in parasite richness with biodiversity loss. In empirical food webs with random removals of free-living species, the relationship between free-living species richness and parasite richness was, on average, quasi-linear, suggesting biodiversity loss reduces parasite diversity more than previously thought.