Parasite co-structure: broad and local scale approaches

A co-structure study is a comparison of demographic and/or genetic structure between two or more species. Such a comparative analysis among a parasite and its host(s) or among multiple parasite species is useful to elucidate factors that shape genetic variation within and among parasite populations. I provide a brief review of how co-structure studies in parasite systems can be used to address ecological, evolutionary, and epidemiological questions. Subjects that can be addressed with parasite costructure studies range from broad-scale analyses that compare phylogeographical patterns to local scale analyses that examine among host transmission within a host population.     

The host of parasites--the ecological approach

As in some studies the opinion that "the host is a biotope for the parasite, mediating its interactions with the environment" is a frequent occurrence, this paper is an attempt to point out the origin of this error and to present the theoretical basis for the accurate approach to these notions, namely parasite and host.     

A fresh look at the origin of Plasmodium falciparum, the most malignant malaria agent

From which host did the most malignant human malaria come: birds, primates, or rodents? When did the transfer occur? Over the last half century, these have been some of the questions up for debate about the origin of Plasmodium falciparum, the most common and deadliest human malaria parasite, which is responsible for at least one million deaths every year. Recent findings bring elements in favor of a transfer from great apes, but are these evidences really solid? What are the grey areas that remain to be clarified? Here, we examine in depth these new elements and discuss how they modify our perception of the origin and evolution of P. falciparum. We also discuss the perspectives these new discoveries open.     

The pathogenesis of cryptosporidiosis

Human infection with the protozoan parasite Cryptosporidium parvum has recently emerged as a global public health problem. Although infection is unrelenting in patients classically regarded as immunocompromised, a tantalizing observation is that infection with this parasite results in both acute self-limited as well as chronic diarrhea in young children. Recent data have begun to elucidate multiple potential mechanisms by which parasitism of the intestinal epithelium may yield an intestinal secretory response. However, a central issue for future studies is to understand how Cryptosporidium infection in young children results in such a broad spectrum of clinical presentation. An answer to this question is likely to result through a dual understanding of how systemic or enteric immunity impacts on intestinal secretory responses and how intra-cellular parasitism alters intestinal epithelial cell function and signals the submucosal intestinal compartment. The virulence factors of Cryptosporidium mediating these events need to be identified. Douglas Clark and Cynthia Sears here review the current understanding of the pathogenesis of intestinal secretion in response to Cryptosporidium infection, and discuss key questions requiring additional study.     

The role of parasites and pathogens in influencing generalised anxiety and predation-related fear in the mammalian central nervous system

This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and Disease." Behavioural and neurophysiological traits and responses associated with anxiety and predation-related fear have been well documented in rodent models. Certain parasites and pathogens which rely on predation for transmission appear able to manipulate these, often innate, traits to increase the likelihood of their life-cycle being completed. This can occur through a range of mechanisms, such as alteration of hormonal and neurotransmitter communication and/or direct interference with the neurons and brain regions that mediate behavioural expression. Whilst some post-infection behavioural changes may reflect 'general sickness' or a pathological by-product of infection, others may have a specific adaptive advantage to the parasite and be indicative of active manipulation of host behaviour. Here we review the key mechanisms by which anxiety and predation-related fears are controlled in mammals, before exploring evidence for how some infectious agents may manipulate these mechanisms. The protozoan Toxoplasma gondii, the causative agent of toxoplasmosis, is focused on as a prime example. Selective pressures appear to have allowed this parasite to evolve strategies to alter the behaviour in its natural intermediate rodent host. Latent infection has also been associated with a range of altered behavioural profiles, from subtle to severe, in other secondary host species including humans. In addition to enhancing our knowledge of the evolution of parasite manipulation in general, to further our understanding of how and when these potential changes to human host behaviour occur, and how we may prevent or manage them, it is imperative to elucidate the associated mechanisms involved.     

Early variations of host thyroxine and interleukin-7 favor Schistosoma mansoni development

Schistosoma mansoni induces, in the vertebrate host, cutaneous production of interleukin-7 (IL-7), which is beneficial for parasite establishment and development. Infection of mice deficient in IL-7 expression leads to parasite dwarfism. Because similar findings were previously described in hypothyroid mice, this study aimed to elucidate the potential link between IL-7 and thyroid hormones (THs), using several models including hypo- and hyperthyroid mice, modified either transiently or constitutively. Mice treated with thyroxine led to increased worm numbers and development of giant worms, whereas an iodine-deficient diet reduced parasite maturation, egg laying, and liver pathology. Conversely, mice genetically deficient for either of the nuclear TH receptors displayed normal worm development despite modifications in hormone levels, suggesting that thyroxine action is mediated through host receptors. In addition, no modification of antibody titers has been evidenced in thyroxine-treated mice, whereas antibody levels were altered in transgenic animals. These observations suggest that the immune system is not likely to be involved in the modifications of parasite development reported in this study. Interestingly, concomitant treatment with IL-7 and thyroxine had a synergistic effect, leading to recovery of very large worms, thus raising questions about the complexity of interactions between IL-7 and metabolic hormones.     

The comparative ecology and biogeography of parasites

Comparative ecology uses interspecific relationships among traits, while accounting for the phylogenetic non-independence of species, to uncover general evolutionary processes. Applied to biogeographic questions, it can be a powerful tool to explain the spatial distribution of organisms. Here, we review how comparative methods can elucidate biogeographic patterns and processes, using analyses of distributional data on parasites (fleas and helminths) as case studies. Methods exist to detect phylogenetic signals, i.e. the degree of phylogenetic dependence of a given character, and either to control for these signals in statistical analyses of interspecific data, or to measure their contribution to variance. Parasite–host interactions present a special case, as a given trait may be a parasite trait, a host trait or a property of the coevolved association rather than of one participant only. For some analyses, it is therefore necessary to correct simultaneously for both parasite phylogeny and host phylogeny, or to evaluate which has the greatest influence on trait expression. Using comparative approaches, we show that two fundamental properties of parasites, their niche breadth, i.e. host specificity, and the nature of their life cycle, can explain interspecific and latitudinal variation in the sizes of their geographical ranges, or rates of distance decay in the similarity of parasite communities. These findings illustrate the ways in which phylogenetically based comparative methods can contribute to biogeographic research.     

Chemical defence in avian brood parasites: production and function of repulsive secretions in common cuckoo chicks

The use of active chemical defence against predators is relatively rare in birds. Among others, it has been reported for some members of family Cuculidae whose chicks, when threatened, expel dark foul‐smelling liquid from their cloaca. Apart from the brood parasitic great spotted cuckoo Clamator glandarius, however, this phenomenon has not yet been systematically studied in any other cuckoo species. Here we investigated the repellent behaviour in the evicting brood parasite, the common cuckoo Cuculus canorus, parasitizing the great reed warbler Acrocephalus arundinaceus. We explored whether production of secretions varies with chick age or size, and tested its presumed repellent function against various types of predators. We found that the production of secretions commenced at the age of approximately eight days, then gradually increased and decreased again shortly before fledging. Furthermore, we experimentally confirmed a more intensive repellent effect of the secretions on mammal predators than on avian predators, such as raptors and owls. The secretions have, however, no effect on corvid predators, probably because these scavengers often consume malodorous food. Further experimental studies together with phylogenetic comparative analyses are needed to elucidate the origin and function of this intriguing phenomenon both in parasitic and non‐parasitic cuckoos.     

Does Trypanosoma cruzi calreticulin modulate the complement system and angiogenesis?

Calreticulin, a calcium-binding protein that is highly conserved in its multiple functions, is present in a wide spectrum of subcellular compartments in virtually every cell of higher organisms. In this article, we propose a dual role for parasite calreticulin, with emphasis on the Trypanosoma cruzi model. By modulating the vertebrate complement system, calreticulin might provide the parasite with an effective immune-escape mechanism. Alternatively, by inhibiting angiogenesis, the parasite molecule might protect the host from ongoing neoplasic aggressions. Many questions are still unanswered, particularly those regarding the consequences that these interactions could have in vivo for both the parasite and the host.     

Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities

Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.     

Evidence for trafficking of PfEMP1 to the surface of P. falciparum-infected erythrocytes via a complex membrane network

The human malarial parasite Plasmodium falciparum exports virulence determinants, such as the P. falciparum erythrocyte membrane protein 1 (PfEMP1), beyond its own periplasmatic boundaries to the surface of its host erythrocyte. This is remarkable given that erythrocytes lack a secretory pathway. Here we present evidence for a continuous membrane network of parasite origin in the erythrocyte cytoplasm. Co-localizations with antibodies against PfEMP1, PfExp-1, Pf332 and PfSbpl at the light and electron microscopical level indicate that this membrane network is composed of structures that have been previously described as tubovesicular membrane network (TVM), Maurer's clefts and membrane whorls. This membrane network could also be visualized in vivo by vital staining of infected erythrocytes with the fluorescent dye LysoSensor Green DND-153. At sites where the membrane network abuts the erythrocyte plasma membrane we observed small vesicles of 15-25 nm in size, which seem to bud from and/or fuse with the membrane network and the erythrocyte plasma membrane, respectively. On the basis of our data we hypothesize that this membrane network of parasite origin represents a novel secretory organelle that is involved in the trafficking of PfEMP1 across the erythrocyte cytoplasm.     

Observations on Echinococcus granulosus of cattle origin in Switzerland

Switzerland is one of the few countries where high fertility rates have been reported in cattle hydatid cysts and where the cattle/dog cycle is the most important for the maintenance of Echinococcus granulosus. The developmental and morphological characteristics of E. granulosus of Swiss cattle origin were studied and compared with that of E. granulosus of domestic animal origin from Great Britain and Australia, countries where bovine hydatid cysts are usually sterile and cattle play little role in the life-cycle of the parasite. Adult E. granulosus of Swiss cattle origin differed markedly in its developmental characteristics compared to other isolates, particularly in its rate of maturation in dogs, producing eggs as early as 35 days post-infection. The morphology of E. granulosus of Swiss cattle origin was characteristic and it could be easily distinguished from other isolates of the parasite. Further, E. granulosus of Swiss cattle origin was found to closely resemble that occurring in cattle in South Africa where high fertility rates have also been reported in bovine hydatid cysts. It is concluded that a strain of E. granulosus exists which is adapted to cattle and that further studies are required to determine whether this strain warrants formal taxonomic status as the species E. ortleppi which was originally described for the parasite of South African cattle origin.     

Giardia: highly evolved parasite or early branching eukaryote?

The phylogeny of the commonest protozoal agent of intestinal disease, Giardia, is unclear. Although recent intensive research suggests this important human parasite is an early branching eukaryote that evolved before the endosymbiotic origin of mitochondria, there is also evidence to suggest that, as a highly evolved parasite, it has lost many of its ancestral characteristics. In this case, these organisms might have arisen much more recently from aerobic free-living flagellates.     

Peroxidoxins: a new antioxidant family

Peroxidoxins are a recently described family of antioxidants. They have an ancient origin, being present in organisms as primitive as the archaea, and they appear to be ubiquitous in living cells. Here, Sharon McGonigle, John Dalton and Eric James review the present understanding of the functions and mechanism of action of these enzymes and suggest that these antioxidants may represent the ;missing link' in the metabolism of reactive oxygen species by some protozoan and helminth parasites. Also, by performing sequence comparisons of homologues entered in the public databases, they have classified the parasite peroxidoxins as 1-cys or 2-cys enzymes. The discovery of these antioxidants may change our understanding of how reactive oxygen species, of parasite or host origin, are managed by parasites.     

Export of proteins via a novel secretory pathway.

The intraerythrocytic location of the malaria parasite necessitates modification of the host cell. These alterations are mediated either directly or indirectly by parasite proteins exported to specific compartments within the host cell. However, little is known about how the parasite specifically targets proteins to locations beyond its plasma membrane. Mark Wiser, Norbert Lanners and Richard Bafford here propose an alternative secretory pathway for the export of parasite proteins into the host erythrocyte. The first step of this pathway is probably an endoplasmic reticulum (ER)-like organelle that is distinct from the normal ER. Possible mechanisms of protein trafficking in the infected erythrocyte are also discussed. The proposed ER-like organelle and alternative secretory pathway raise many questions about the cell biology of protein export and trafficking in Plasmodium.     

3-D analysis of the Plasmodium falciparum Maurer's clefts using different electron tomographic approaches

The human malaria parasite Plasmodium falciparum exports a large number of proteins into its host erythrocyte to install functions necessary for parasite survival. Important structural components of the export machinery are membrane profiles of parasite origin, termed Maurer's clefts. These profiles span much of the distance between the parasite and the host cell periphery and are believed to deliver P. falciparum-encoded proteins to the erythrocyte plasma membrane. Although discovered more than a century ago, Maurer's clefts remain a mysterious organelle with little information available regarding their origin, their morphology or their precise role in protein trafficking. Here, we evaluated different techniques to prepare samples for electron tomography, including whole cell cryo-preparations, vitreous sections, freeze-substitution and chemical fixation. Our data show that the different approaches tested all have their merits, revealing different aspects of the complex structure of the Maurer's clefts.     

Parasite phylogeographical congruence with salmon host evolutionarily significant units: implications for salmon conservation

Comparative phylogeographical studies between parasites and their hosts or with biogeographical regions are useful to predict parasite dispersal potential over a broad geographical range. We used both microsatellite markers and mtDNA sequence data from a trematode parasite, Plagioporus shawi, to test for congruence across two evolutionarily significant unit (ESU) boundaries of its salmonid hosts (Oncorhynchus spp.). We find congruent patterns with the nuclear loci of P. shawi and the ESU boundaries of its salmonid hosts. This pattern indicates that broad-scale phylogeographical patterns of a parasite can be predicted by the biogeographical history of their hosts. Furthermore, this pattern provides independent support for these ESU boundaries as biologically relevant barriers. The mtDNA shows some discordance with nuclear loci and a level of genetic differentiation greater than can be explained by genetic drift. Thus, the mtDNA cannot be used in isolation to infer the population history of P. shawi. The genetic differentiation at both the nuclear and mtDNA markers will be useful for salmon fisheries management by providing a tool to assign ocean-migrating salmonids back to their freshwater population of origin.     

Endocytosis,cadherins and tissue dynamics

By happy chance, the founding of Traffic in 1999 coincided with a clutch of reports that documented the endocytosis and recycling of classical cadherin adhesion receptors. This stimulated a concerted effort to elucidate the molecular regulation of cadherin endocytosis and to identify its functional implications. In particular, endocytosis provided new perspectives to understand how cadherins are modulated during tissue morphogenesis. In this short article, we consider some of what we have learnt about this problem and identify open questions for future research.     

Host patch traits have scale-dependent effects on diversity in a stickleback parasite metacommunity

Many metacommunities are distributed across habitat patches that are themselves aggregated into groups. Perhaps the clearest example of this nested metacommunity structure comes from multi-species parasite assemblages, which occupy individual hosts that are aggregated into host populations. At both spatial scales, we expect parasite community diversity in a given patch (either individual host or population) to depend on patch characteristics that affect colonization rates and species sorting. But, are these patch effects consistent across spatial scales? Or, do different processes govern the distribution of parasite community diversity among individual hosts, versus among host patches? To answer these questions, we document the distribution of parasite richness among host individuals and among populations in a metapopulation of threespine stickleback Gasterosteus aculeatus. We find some host traits (host size, gape width) are associated with increased parasite richness at both spatial scales. Other patch characteristics affect parasite richness only among individuals (sex), or among populations (lake size, lake area, elevation and population mean heterozygosity). These results demonstrate that some rules governing parasite richness in this metacommunity are shared across scales, while others are scale-specific.