Mining the Plasmodium genome database to define organellar function: what does the apicoplast do?

Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for a wide range of diseases in many organisms. Despite differences in the diseases they cause, these parasites share an underlying biology, from the genetic controls used to differentiate through the complex parasite life cycle, to the basic biochemical pathways employed for intracellular survival, to the distinctive cell biology necessary for host cell attachment and invasion. Different parasites lend themselves to the study of different aspects of parasite biology: Eimeria for biochemical studies, Toxoplasma for molecular genetic and cell biological investigation, etc. The Plasmodium falciparum Genome Project contributes the first large-scale genomic sequence for an apicomplexan parasite. The Plasmodium Genome Database (http://PlasmoDB.org) has been designed to permit individual investigators to ask their own questions, even prior to formal release of the reference P. falciparum genome sequence. As a case in point, PlasmoDB has been exploited to identify metabolic pathways associated with the apicomplexan plastid, or 'apicoplast' - an essential organelle derived by secondary endosymbiosis of an alga, and retention of the algal plastid.     

Intravital imaging of host‐parasite interactions in organs of the thoracic and abdominopelvic cavities

Infections with protozoan and helminthic parasites affect multiple organs in the mammalian host. Imaging pathogens in their natural environment takes a more holistic view on biomedical aspects of parasitic infections. Here, we focus on selected organs of the thoracic and abdominopelvic cavities most commonly affected by parasites. Parasitic infections of these organs are often associated with severe medical complications or have health implications beyond the infected individual. Intravital imaging has provided a more dynamic picture of the host–parasite interplay and contributed not only to our understanding of the various disease pathologies, but has also provided fundamental insight into the biology of the parasites.     

Diversification and host switching in avian malaria parasites

The switching of parasitic organisms to novel hosts, in which they may cause the emergence of new diseases, is of great concern to human health and the management of wild and domesticated populations of animals. We used a phylogenetic approach to develop a better statistical assessment of host switching in a large sample of vector-borne malaria parasites of birds (Plasmodium and Haemoproteus) over their history of parasite-host relations. Even with sparse sampling, the number of parasite lineages was almost equal to the number of avian hosts. We found that strongly supported sister lineages of parasites, averaging 1.2% sequence divergence, exhibited highly significant host and geographical fidelity. Event-based matching of host and parasite phylogenetic trees revealed significant cospeciation. However, the accumulated effects of host switching and long distance dispersal cause these signals to disappear before 4% sequence divergence is achieved. Mitochondrial DNA nucleotide substitution appears to occur about three times faster in hosts than in parasites, contrary to findings on other parasite-host systems. Using this mutual calibration, the phylogenies of the parasites and their hosts appear to be similar in age, suggesting that avian malaria parasites diversified along with their modern avian hosts. Although host switching has been a prominent feature over the evolutionary history of avian malaria parasites, it is infrequent and unpredictable on time scales germane to public health and wildlife management.     

Chemokines and chemokine receptors: Insights from human disease and experimental models of helminthiasis

Infection with helminth parasites affects more than 1.5 billion people and is concentrated in global areas of extreme poverty, having a significant impact on public health, social life and the economy. Upon entry into the host, helminth parasites often migrate through specific tissues triggering host immunity. The immune response triggered by helminth infections is complex and depends on parasite load, site of infection, acuteness/chronicity of the infection and is species-dependent. In general, susceptibility or resistance to the infection involves the participation of the innate immune response and then the balance between several effector CD4⁺ T cells subsets, such as Th1, Th2, Th9, Th17, Tfh and Treg, coordinated by immune mediators such as cytokines and chemokines. Chemokines guide the recruitment and activation of leukocytes under inflammatory and homeostatic states. The chemokine system has been associated with several diseases and experimental models with a significant inflammatory component, including infection with helminth parasites. Therefore, this critical review will highlight the main findings concerning chemokine responses elicited by the interaction between helminth parasites and the hosts’ immune system, hence contributing to the understanding of the relevance of chemokine synthesis and biology in the immunological response to infection by parasitic helminths.     

寄生虫基因组学研究进展

寄生虫病严重危害人和动物的健康,但目前防治寄生虫病尚存在困难,随着分子生物学技术的迅速发展,运用分子生物学技术手段来控制寄生虫病将成为可能.本文主要介绍寄生虫基因的组成及特征、目前的测序现状、基因组测序、分析、基因功能及蛋白质组的研究技术等,可为寄生虫种类鉴定、寄生虫病诊断、药物设计和疫苗研制提供新的方向.     

Host traits,identity, and ecological conditions predict consistent flea abundance and prevalence on free-living California ground squirrels

Understanding why some individuals are more prone to carry parasites and spread diseases than others is a key question in biology. Although epidemiologists and disease ecologists increasingly recognize that individuals of the same species can vary tremendously in their relative contributions to the emergence of diseases, very few empirical studies systematically assess consistent individual differences in parasite loads within populations over time. Two species of fleas (Oropsylla montana and Hoplopsyllus anomalous) and their hosts, California ground squirrels (Otospermophilus beecheyi), form a major complex for amplifying epizootic plague in the western United States. Understanding its biology is primarily of major ecological importance and is also relevant to public health. Here, we capitalize on a long-term data set to explain flea incidence on California ground squirrels at Briones Regional Park in Contra Costa County, USA. In a 7 year study, we detected 42,358 fleas from 2,759 live trapping events involving 803 unique squirrels from two free-living populations that differed in the amount of human disturbance in those areas. In general, fleas were most abundant and prevalent on adult males, on heavy squirrels, and at the pristine site, but flea distributions varied among years, with seasonal conditions (e.g., temperature, rainfall, humidity), temporally within summers, and between flea species. Although on-host abundances of the two flea species were positively correlated, each flea species occupied a distinctive ecological niche. The common flea (O. montana) occurred primarily on adults in cool, moist conditions in early summer whereas the rare flea (H. anomalous) was mainly on juveniles in hot, dry conditions in late summer. Beyond this, we uncovered significantly repeatable and persistent effects of host individual identity on flea loads, finding consistent individual differences among hosts in all parasite measures. Taken together, we reveal multiple determinants of parasites on free-living mammals, including the underappreciated potential for host heterogeneity – within populations – to structure the emergence of zoonotic diseases such as bubonic plague.     

Molecular cross-talk in host-parasite relationships: the intriguing immunomodulatory role of Echinococcus antigen B in cystic echinococcosis

Cystic echinococcosis (CE), a zoonosis caused by the development of Echinococcus granulosus tapeworm larvae in the internal organs of ungulates and humans, continues to pose a major public health burden in underdeveloped and industrialised areas worldwide. Research designed to improve parasitic disease control and find out more about parasite biology has already identified a number of E. granulosus antigenic molecules. The major E. granulosus immunomodulant antigen isolated from hydatid fluid is antigen B, a 120kDa polymeric lipoprotein consisting of various 8kDa subunits. By inhibiting elastase activity and neutrophil chemotaxis and eliciting a non-protective Th2 cell response, antigen B helps the parasite evade the human response. In this review, we briefly discuss current information on the molecular characteristics and immunomodulatory properties of E. granulosus antigen B. Besides focusing on findings that provide intriguing insights into the complex interplay between host and parasite, we suggest how this information could extend the current therapeutic options in inflammatory diseases.     

Information about transmission opportunities triggers a life-history switch in a parasite

Many microbial pathogens can switch to new hosts or adopt alternative transmission routes as environmental conditions change, displaying unexpected flexibility in their infection pathways and often causing emerging diseases. In contrast, parasitic worms that must develop through a fixed series of host species appear less likely to show phenotypic plasticity in their transmission pathways. Here, I demonstrate experimentally that a trematode parasite, Coitocaecum parvum, can accelerate its development and rapidly reach precocious maturity in its crustacean intermediate host in the absence of chemical cues emanating from its fish definitive host. Juvenile trematodes can also mature precociously when the mortality rate of their intermediate hosts is increased. Eggs produced by precocious adults hatch into viable larvae, capable of pursuing the parasite's life cycle. In the absence of chemical cues from fish hosts, the size of eggs released by precocious trematodes in their intermediate hosts becomes more variable, possibly indicating a bet-hedging strategy. These results illustrate that parasitic worms with complex life cycles have development and transmission strategies that are more plastic than commonly believed, allowing them to skip one host in their cycle when they perceive limited opportunities for transmission.     

Parasites of the superorganism: are they indicators of ecosystem health?

The concept of ecosystem health is derived from analogies with human health, which subsequently leads to the implication that the ecosystem has organismal properties, a 'superorganism' in the Clementsian sense. Its application and usefulness has been the subject of a contentious debate; yet, the term 'ecosystem health' has captured the public's imagination and woven its way into the current lexicon, even incorporated into public policy. However, the application of parasites as bioindicators of ecosystem health poses a curious conundrum. Perceptions of parasites range from mild distaste to sheer disgust among the general public, the media, environmental managers and non-parasitologists in the scientific community. Nevertheless, the biological nature of parasitism incorporates natural characteristics that are informative and useful for environmental management. The helminths in particular have evolved elegant means to ensure their transmission, often relying on complex life cycle interactions that include a variety of invertebrate and vertebrate hosts. The assemblage of these diverse parasites within a host organism potentially reflect that host's trophic position within the food web as well as the presence in the ecosystem of any other organisms that participate in the various parasite life cycles. Perturbations in ecosystem structure and function that affect food web topology will also impact upon parasite transmission, thus affecting parasite species abundance and composition. As such, parasite populations and communities are useful indicators of environmental stress, food web structure and biodiversity. In addition, there may be useful other means to utilise parasitic organisms based on their biology and life histories such as suites or guilds that may be effective bioindicators of particular forms of environmental degradation. The challenge for parasitology is to convince resource managers and fellow scientists that parasites are a natural part of all ecosystems, each species being a potentially useful information unit, and that healthy ecosystems have healthy parasites.     

The biology of the heat shock response in parasites

The heat shock response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stress. It has been shown that heat shock proteins play major roles in many cellular processes and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology and from cancer research to interactions between host and parasite. In this review, Bruno Maresca and Luisella Carratu deal with some of the unique characteristics of the heat shock response in parasitic organisms.     

Nematodes as host resistance models for detection of immunotoxicity

Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. The focus of this paper is resistance to infection with the parasitic nematode Trichinella spiralis as a model of host resistance. Topics include overviews of parasite biology, host immune responses that limit infection and methods used to evaluate the host response to infection. Detailed protocols are provided for adult and larval parasite counts, female parasite fecundity, parasite antigen-driven lymphocyte proliferation and antibody responses to infection.     

Advances in drug discovery and biochemical studies

Japanese researchers continue to discover new means to combat parasites and make important contributions toward developing tools for global control of parasitic diseases. Streptomyces avermectinius, the source of ivermectin, was discovered in Japan in the early 1970s and renewed and vigorous screening of microbial metabolites in recent years has led to the discovery of new antiprotozoals and anthelminthics, including antimalarial drugs. Intensive studies of parasite energy metabolism, such as NADH-fumarate reductase systems and the synthetic pathways of nucleic acids and amino acids, also contribute to the identification of novel and unique drug targets.     

Using ecological stoichiometry to understand and predict infectious diseases

A key characteristic of host–parasite interactions is the theft of host nutrients by the parasite, yet we lack a general framework for understanding and predicting the interplay of host and parasite nutrition that applies across biological levels of organization. The elemental nutrients (C, N, P, Fe, etc.), and ecological stoichiometry provide a framework for understanding host–parasite interactions and their relation to ecosystem functioning. Here we use the ecological stoichiometry framework to develop hypotheses and predictions regarding the relationship between elemental nutrients and host–parasite interactions. We predict that a suite of host and parasite traits, stoichiometric homeostasis, host diet stoichiometry, and biogeochemical cycling are related to disease dynamics, host immunity and resistance, and bacterial growth form determination. We show that ecological stoichiometry is capable of expanding our understanding of host–parasite interactions, and complementing other approaches such as population and community ecology, and molecular biology, for studying infectious diseases.     

Tsetse flies,trypanosomes, humans and animals: what is proteomics revealing about their crosstalks?

Human and animal African trypanosomoses, or sleeping sickness and Nagana, are neglected vector-borne parasitic diseases caused by protozoa belonging to the Trypanosoma genus. Advances in proteomics offer new tools to better understand host–vector–parasite crosstalks occurring during the complex parasitic developmental cycle, and to determine the outcome of both transmission and infection. In this review, we summarize proteomics studies performed on African trypanosomes and on the interactions with their vector and mammalian hosts. We discuss the contributions and pitfalls of using diverse proteomics tools, and argue about the interest of pathogenoproteomics, both to generate advances in basic research on the best knowledge and understanding of host–vector–pathogen interactions, and to lead to the concrete development of new tools to improve diagnosis and treatment management of trypanosomoses in the near future.     

Polyamine transport in parasites: a potential target for new antiparasitic drug development

The metabolism of the naturally occurring polyamines-putrescine, spermidine and spermine-is a highly integrated system involving biosynthesis, uptake, degradation and interconversion. Metabolic differences in polyamine metabolism have long been considered to be a potential target to arrest proliferative processes ranging from cancer to microbial and parasitic diseases. Despite the early success of polyamine inhibitors such as alpha-difluoromethylornithine (DFMO) in treating the latter stages of African sleeping sickness, in which the central nervous system is affected, they proved to be ineffective in checking other major diseases caused by parasitic protozoa, such as Chagas' disease, leishmaniasis or malaria. In the use and design of new polyamine-based inhibitors, account must be taken of the presence of up-regulated polyamine transporters in the plasma membrane of the infectious agent that are able to circumvent the effect of the drug by providing the parasite with polyamines from the host. This review contains information on the polyamine requirements and molecular, biochemical and genetic characterization of different transport mechanisms in the parasitic agents responsible for a number of the deadly diseases that afflict underdeveloped and developing countries.     

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

Intravital microscopy allows imaging of biological phenomena within living animals, including host–parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host–parasite interactions within organs at depths, speeds and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarise technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen and the mucosa‐associated lymphoid tissue, and present a view into possible future applications.     

Social parasites among African allodapine bees (Hymenoptera,Anthophoridae, Ceratinini)*

Among the numerous nonparasitic allodapine bees there are 11 known species with parasitic or probably parasitic habits. These species live in nests of their close relatives, the female parasite replacing an egg-layer of the host. Seven of the parasitic species are distributed among four otherwise nonparasitic genera, while four species of parasites are placed in three exclusively parasitic genera. The parasites have mostly arisen independently from different nonparasitic forms. There is much convergence among the parasitic forms involving such characters as the flattened or concave face, reduced eyes, reduced mouthparts, reduced wing venation, and reduced pollen-carrying scopa. In the most specialized parasitic genera the mouthparts are so small as to be almost surely useless for obtaining food from flowers. Such bees must feed in the host nest, and are not found on flowers. Their wings must be adequate to take them to a new host nest but the reduced venation and eyes must reflect the reduced locomotary and sensory needs of a bee that does not visit flowers. In this paper a new, presumably parasitic Allodapula is described as is a parasitic Braunsapis, a parasitic Allodape, and a Eucondylops. A previously described Macrogalea is recognized as a parasite for the first time. A new genus and species of parasites Nasutapsis straussorum, allied to Braunsapis, is also described. All these forms are from Africa.