Role of the long slender to short stumpy transition in the life cycle of the african trypanosomes

It is shown using mouse models that the African trypanosomes exert a significant drain upon their host's carbohydrate (energy) resources; and that the higher the parasitemia, the greater the energy demand. It is, therefore, hypothesized that the long slender (LS) to short stumpy (SS) transition evolved, in part, to help control the parasitemia and to increase host survival time. It is also suggested that the SS population is heterogeneous. One part of the population is tsetse infective, while a second older SS population is undergoing apoptotic-like events, which leads to their cell death and their stimulation of the host's immune response. This immune stimulation by the old dying SS forms would eliminate the major LS and SS variant antigen population, and produce the chronic relapsing infection. It is concluded that the SS stages during the apoptosis-like process are acting altruistically. They give their lives to insure the long-term survival of the host, and to insure renewed growth of the minor LS variants and new infective SS forms. This process is predicted to increase the probability for the successful transmission of the trypanosomes to a new host.     

The ins,outs and roundabouts of malaria

The malaria parasite Plasmodium falciparum is a complex eukaryote parasite with a dynamic pattern of genomic expression, enabling it to exploit a series of different habitats in human and mosquito hosts. In the human bloodstream, the parasite grows and multiplies within red blood cells and modifies them in various ways to gain nutrients and combat the host's defences, before escaping and invading new red blood cells by a multi-step process. These events are reflected in the constantly changing structure of the organism during the red blood cell cycle.     

Intracellular protozoan parasites and apoptosis: diverse strategies to modulate parasite-host interactions

Programmed cell death (apoptosis) is an important regulator of the host's response during infection with a variety of intracellular protozoan parasites. Parasitic pathogens have evolved diverse strategies to induce or inhibit host-cell apoptosis, thereby modulating the host's immune response, aiding dissemination within the host or facilitating intracellular survival. Here, we review the molecular and cell-biological mechanisms of the pathogen-induced modulation of host-cell apoptosis and its effects on the parasite-host interaction and the pathogenesis of parasitic diseases. We also discuss the previously unrecognized phenomenon of apoptotic cell death in (unicellular) protozoan parasites and its potential implications.     

Cryptosporidia: epicellular parasites embraced by the host cell membrane

The ultrastructure of two gastric cryptosporidia, Cryptosporidium muris from experimentally infected rodents (Mastomys natalensis) and Cryptosporidium sp. 'toad' from naturally infected toads (Duttaphrynus melanostictus), was studied using electron microscopy. Observations presented herein allowed us to map ultrastructural aspects of the cryptosporidian invasion process and the origin of a parasitophorous sac. Invading parasites attach to the host cell, followed by gradual envelopment, with the host's cell membrane folds, eventually forming the parasitophorous sac. Cryptosporidian developmental stages remain epicellular during the entire life cycle. The parasite development is illustrated in detail using high resolution field emission scanning electron microscopy. This provides a new insight into the ultrastructural detail of host-parasite interactions and species-specific differences manifested in frequency of detachment of the parasitophorous sac, radial folds of the parasitophorous sac and stem-formation of the parasitised host cell.     

The Invasive Nature of an Infectious Bacterial Symbiont

ABSTRACT. Xenosomes are infectious bacterial symbionts that exist exclusively in the cytoplasm of the small philasterine marine ciliate Parauronema acutum. We have used this host-symbiont system as a model to study infection. In the past we postulated that infection took place by a process in which the symbionts escaped digestion and entered into the host's cytoplasm through the food vacuole during phagocytosis. This is clearly not the case. We now present evidence based on electron microscopic observations that the symbionts infect in a manner involving direct penetration of the protozoan's cell membranes. We have obtained additional data that suggest that, following entrance of the symbionts into the cytoplasm, only a single xenosome is required to establish an infection.     

Shared control of epidemiological traits in a coevolutionary model of host-parasite interactions

Most models concerning the evolution of a parasite's virulence and its host's resistance assume that each component of the relationship (transmission, virulence, recovery, etc.) is controlled by either the host or the parasite but not by both. We present a model that describes the coevolution of host and parasite, assuming that the rate of transmission or the virulence depends on both genotypes. The evolution of these traits is constrained by trade-offs that account for costs of defense and attack strategies, in line with previous studies on the separate evolution of the host and the parasite. Considering shared control by the host and the parasite in determining the traits of the relationship leads to several novel predictions. First, the host should evolve maximal investment in defense against parasites with an intermediate replication rate. Second, the evolution of the parasite strongly depends on the way the host's defense is described. Third, the coevolutionary process may lead to decreasing the parasite's virulence as a response to a rise in the host's background mortality, contrary to classical predictions.     

Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form

African trypanosomes produce some prostanoids, especially PGD2, PGE2 and PGF2alpha (Kubata et al. 2000, J. Exp. Med. 192: 1327-1338), probably to interfere with the host's physiological response. However, addition of prostaglandin D2 (but not PGE2 or PGF2alpha) to cultured bloodstream form trypanosomes led also to a significant inhibition of cell growth. Based on morphological alterations and specific staining methods using vital dyes, necrosis and autophagy were excluded. Here, we report that in bloodstream form trypanosomes PGD2 induces an apoptosis-like programmed cell death, which includes maintenance of plasma membrane integrity, phosphatidylserine exposure, loss of mitochondrial membrane potential, nuclear chromatin condensation and DNA degradation. The use of caspase inhibitors cannot prevent the cell death, indicating that the process is caspase-independent. Based on these results, we suggest that PGD2-induced programmed cell death is part of the population density regulation as observed in infected animals.     

Protein trafficking in Plasmodium falciparum-infected red blood cells

Plasmodium falciparum inhabits a niche within the most highly terminally differentiated cell in the human body--the mature red blood cell. Life inside this normally quiescent cell offers the parasite protection from the host's immune system, but provides little in the way of cellular infrastructure. To survive and replicate in the red blood cell, the parasite exports proteins that interact with and dramatically modify the properties of the host red blood cell. As part of this process, the parasite appears to establish a system within the red blood cell cytosol that allows the correct trafficking of parasite proteins to their final cellular destinations. In this review, we examine recent developments in our understanding of the pathways and components involved in the delivery of important parasite-encoded proteins to their final destination in the host red blood cell. These complex processes are not only fundamental to the survival of malaria parasites in vivo, but are also major determinants of the unique pathogenicity of this parasite.     

Mitogenic effect of muscle on the neuroepithelium of the developing spinal cord

A previous study revealed that segments of bowel grafted between the neural tube and somites of a younger chick host embryo would induce a unilateral increase in cellularity of the host's neural tube. The current experiments were done to test the hypotheses that muscle tissue in the wall of the gut is responsible for this growth-promoting effect and that the spinal cord enlargement is the result of a mitogenic action on the neuroepithelium. Fragments of skeletal (E8-15) or cardiac muscle (E4-14) were removed from quail embryos and grafted between the neural tube and somites of chick host embryos (E2). Both skeletal and cardiac muscle grafts mimicked the effect of bowel and induced an increase in cell number as well as a unilateral enlargement of the region of the host's neural tube immediately adjacent to the grafts. The growth-promoting effect of muscle-containing grafts was restricted to the neural tube itself and was not seen in proximate dorsal root or sympathetic ganglia. The action of the grafts of muscle was neither species- nor class-specific, since enlargement of the neural tube was observed following implantation of fetal mouse skeletal muscle into quail hosts. Grafts of skeletal muscle or gut increased the number of cells taking up [3H]thymidine in the host's neuroepithelium as early as 9 h following implantation of a graft. The increase in the number of cells entering the S phase of the cell cycle preceded the increase in cell number. These observations demonstrate that muscle-containing tissues can increase the rate of proliferation of neuroepithelial cells when these tissues are experimentally placed together.     

How ubiquitination and autophagy participate in the regulation of the cell response to bacterial infection

Bacterial infection relies on the micro-organism's ability to orchestrate the host's cell signalling such that the immune response is not activated. Conversely, the host cell has dedicated signalling pathways for coping with intrusions by pathogens. The autophagy of foreign micro-organisms (known as xenophagy) has emerged as one of the most powerful of these pathways, although the triggering mode remains largely unknown. In the present paper, we discuss the role that certain post-translational modifications (primarily ubiquitination) may play in the activation of xenophagy and how some bacteria have evolved mechanisms to subvert or hijack this process. In particular, we address the role played by P62/SQSTM1 (sequestosome 1). Finally, we discuss how autophagy can be subverted to eliminate bacteria-induced danger signals.     

Cycloheximide induces synchronous swelling of perialgal vacuoles enclosing symbiotic Chlorella vulgaris and digestion of the algae in the ciliate Paramecium bursaria

Cycloheximide is known to inhibit preferentially protein synthesis of symbiotic Chlorella of the ciliate Paramecium bursaria, but to hardly host protein synthesis. Treatment of algae-bearing Paramecium cells with cycloheximide induces synchronous swelling of all perialgal vacuoles that are localized immediately beneath the host's cell membrane. In this study, the space between the symbiotic algal cell wall and the perialgal vacuole membrane widened to about 25 times its normal width 24 h after treatment with cycloheximide. Then, the vacuoles detached from beneath the host's cell membrane, were condensed and stained with Gomori's solution, and the algae in the vacuoles were digested. Although this phenomenon is induced only under a fluorescent light condition, and not under a constant dark condition, this phenomenon was not induced in paramecia treated with cycloheximide in the light in the presence of the photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea. These results indicate that algal proteins synthesized in the presence of algal photosynthesis serve some important function to prevent expansion of the perialgal vacuole and to maintain the ability of the perialgal vacuole membrane to protect itself from host lysosomal fusion.     

Schistosomes, fibroblasts, and growth factors: how a worm causes liver scarring

The traditional concept of tissue scarring as a static pathological endpoint has been replaced by the modern perspective of a potentially reversible process comprising a sequence of discrete biological events (cell recruitment and hyperplasia, excessive matrix production, and matrix degradation). Cytokines, including several produced by inflammatory cells, have been identified that specifically regulate these events. Research into the cellular and molecular biology of scar formation is motivated by clinical and basic scientific considerations. One model of fibrogenesis that is being studied in detail is the liver fibrosis associated with schistosomiasis. In this helminthic infection, the host's granulomatous inflammatory response to the parasite eggs apparently lead to scar formation. A novel lymphokine that is mitogenic for fibroblasts and is produced by CD4+ lymphocytes in the granuloma has been found in infected livers. Preliminary evidence for the existence of immunoregulatory mechanisms of fibrogenesis in this disease also has been obtained. The potential role of genetic determinants that may influence this process needs to be further studied.     

Glucose transport in malaria infected erythrocytes

Intracellular protozoan parasites of the genus Plasmodium spend much of the cell cycle inside the vertebrate host's erythrocytes. Recent studies on the metabolism of D-glucose in Plasmodium-infected erythrocytes have suggested that the parasite does not depend on the glycolytic activity of the host erythrocyte. Kazuyuki Tanabe describes how the intraerythrocytic parasite acquires extracellular D-glucose from the host and the pathways through which the sugar crosses the membranes of both the parasite and the host eruthrocyte. It appears that the parasite adapts itself to the host's physiological environment and modifies the functions of the host erythrocyte to be able to complete intraerythrocytic development.     

The biology and functional anatomy of Modiolarca tumida (Musculus marmoratus) Bivalvia: Mytilidae

Modiolarca tumida (Hanley, 1843) is a member of the sub-family Crenellinae (Mytilidae). The preferred habitat of the species is the test of certain ascidians. The shell is dorsally flattened, which prevents it from cutting into the test during dorso-ventral contraction of the byssal retractors. The use of the byssus enables it to surround itself completely with host tissue. Adoption of the feeding posture involves the anterior-posterior contraction of the byssal retractors, which elevates the posterior margin above the host's surface using the anterior margin as the fulcrum against the host. Modiolarca tumida are attracted by the tunicin of the host, a process probably facilitated by the host's feeding currents. The smallest individuals are found round the oral aperture. Colonization of other parts of the host may result from surface migration as M. tumida can be highly mobile, crawling by means of the very extensible foot. It is during this process that individuals may be swept away in local currents and be forced to adopt a free-living existence.     

Endosymbiosis as a compact ecosystem with material cycling: parasitism or mutualism?

To discover the evolutionary logic of intracellular endosymbiosis, we investigated a theoretical model (simultaneous ordinary differential equations) of a material-cycling system inside a host cell. In the model, we introduced a recently developed cell biology concept called "autophagy", which is a decomposing-recycle process of self-compiled materials found universally among eukaryote cells. Our model is based on traditional simultaneous ODE for natural ecosystems that involve producing, grazing, and decomposing processes in material cycling. In the basic intracellular metabolic system, several enzymes regulate metabolism by synthesizing and converting metabolites into biomolecules that are precursors for enzymes involved in the producing process. Symbionts are involved in grazing processes and autophagosomes that degrade materials are involved in decomposing recycles. We compared and analyzed the local stability of ODE systems in three cases: (1) the independent, free-living cell (the basal state of a cell), (2) the case where symbionts invade and exploit macrobiomaterials as parasites inside a host cell, and (3) the combination where symbionts assist the host's metabolism. We conclude that: (i) as consumers, symbionts are required to have a growth rate that is higher than the rate of autophagosome decomposition, (ii) the host cell with a biomass larger than the threshold size would realize the mutualistic relationship with its symbiont, and (iii) this partnership accelerates the biomaterial turnover flow on the basis of biomaterials.     

The metabolic environment of cancer

The tumor cell has a very distinctive metabolism. It acts as a metabolic trap for host nutrients thus taking vital compounds for the metabolism of the host. Depending on the particular tumor growing pattern, cancer cells use preferentially glucose or amino acids for their energetic or biosynthetic needs. Lipids, fatty acids in particular, can also be taken up by the tumor cell. In addition, it can also release some compounds into the host circulation which are not normally produced by the original cell before neoplastic transformation. Some of these compounds affect the metabolism of the host in an unfavorable way since they can oppose the host's metabolic responses, which sustain homeostasis. The final product is that the metabolic machinery of these cells allows them to grow continuously in an uncontrolled manner. The consequences of tumor invasion on the host's metabolism are varied. They have, however, one thing in common: the reduction of the metabolic efficiency of the host. Muscular protein depletion, increased gluconeogenesis, uncoupling of oxidative phosphorylation constitute the main metabolic responses of the host as a result of tumor invasion. The net result of all these metabolic changes is profound energy imbalance which normally ends with cachexia and, eventually, death.     

A modified Escherichia coli protein production strain expressing staphylococcal nuclease,capable of auto-hydrolysing host nucleic acid

The large-scale production of recombinant biotherapeutics, particularly recombinant proteins, provides significant process and regulatory challenges to the biotechnology industry in order to meet the regulatory agencies stringent requirements in a cost-effective manner. Host cell derived nucleic acid causes problems from both a process and a regulatory perspective, as high molecular weight chromosomal DNA is responsible both for the viscosity of cell lysates, and it is a source of heterologous DNA sequences whose inclusion in the final product must be prevented. We have constructed a modified Escherichia coli JM107 expression host (JMN), containing a staphylococcal nuclease expression cassette, integrated into the host chromosome at the dif locus. The nuclease is expressed as a fusion to the ompA signal peptide, and is translocated to the periplasm of the cell, protecting the cytoplasmic nucleic acid from any toxic activity. The nuclease is released during cell lysis, where it subsequently acts to hydrolyse host nucleic acid present in the lysate. Results with this strain show that sufficient levels of nuclease activity are produced to completely auto-hydrolyse the host's chromosomal DNA to a size non-visible on 1% agarose gel, generating a markedly lower lysate viscosity. This provides a suitable methodology to remove heterologous DNA sequences early in the product stream and decrease lysate viscosity, improving the efficiency of downstream processing and product yield, whilst avoiding the addition of exogenous nuclease and its prohibitive costs at large-scale.     

The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila

Most infections induce anorexia but its function, if any, remains unclear. Because this response is common among animals, we hypothesized that infection-induced diet restriction might be an adaptive trait that modulates the host's ability to fight infection. Two defense strategies protect hosts against infections: resistance, which is the ability to control pathogen levels, and tolerance, which helps the host endure infection-induced pathology. Here we show that infected fruit flies become anorexic and that diet restriction alters defenses, increasing the fly's tolerance to Salmonella typhimurium infections while decreasing resistance to Listeria monocytogenes. This suggests that attempts to extend lifespan through diet restriction or the manipulation of pathways mimicking this process will have complicated effects on a host's ability to fight infections.     

The formation of host-parasite relationships in an experimental mixed pathology of opisthorchiasis-tuberculosis as dependent on the phase of the Opisthorchis infestation]

Superinfection of animals having Opisthorchis invasion with Mycobacterium tuberculosis leads to destabilization of host-parasite relationships in opisthorchiasis and formation of new host-parasitocenotic interrelations whose manifestation depends on the phase of the invasive process. At the acute invasive phase of mixed pathology (2 weeks) the activity of the host's immune system increases, while the biological activity of helminths and the number of M. tuberculosis colonies decrease. And on the contrary, at the subacute phase of mixed pathology (2.5 months) the activity of the host's immune system decreases, while the reproductive activity of helminths and the isolation rate of M. tuberculosis from pulmonary tissue increases in comparison with the groups of animals with monoinvasion and monoinfection.