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Intestinal protozoa infections.

This article reviews important intestinal protozoal infections in cats. Among intestinal protozoa, Giardia and coccidia are the most important infections. Giardiasis is a common problem in catteries, especially where young kittens run free on the floor. Overcrowding and high humidity favour the survival and transmission of Giardia. Diagnosis is made by fecal examination by direct or concentration methods. Metronidazole is the drug of choice for treating giardiasis. Among the coccidial parasites, Isospora felis and Cryptosporidium sp. are the common infections. Virtually all cats become infected with Isospora felis. The pathogenicity of I. felis is controversial. Cryptosporidium parvum infection is a zoonosis. Cryptosporidium is transmitted by direct fecal-oral cycle. Cryptosporidial infections appear to be clinical in immunosuppressed cats. No drug has been found satisfactory for treatment of cryptosporidiosis.

Animals↗

Cytochrome P450 in parasitic protozoa and helminths.

Cytochrome P450 has been demonstrated in flagellate and sporozoan Protozoa. In Plasmodium there is a correlation between chloroquine resistance and cytochrome P450 mono-oxygenase activity, but there is no evidence that the malarial parasite metabolises chloroquine by an oxidative mechanism. There is no evidence for cytochrome P450 in adult helminths (nematodes and platyhelminths) based on P450 content and mono-oxygenase activity with classical substrates, although low activities may be present in free-living larval stages.

Animals↗

Genetic interference in protozoa.

RNA interference first described in Caenorhabditis elegans and transgene-induced post-transcriptional gene silencing first described in plants and fungi now appear as different means of activating a conserved and ancient mechanism that can protect genomes against viruses and transposons and perhaps also control expression of endogenous genes. We present here similar genetic interference phenomena in highly divergent protozoa, Trypanosoma and Paramecium, and look ahead to what contribution these microorganisms could bring to this fast-moving area.

Animals↗

Characterization of the spasmin 1 gene in Zoothamnium arbuscula strain Kawagoe (protozoa, ciliophora) and its relation to other spasmins and centrins.

Zoothamnium arbuscula strain Kawagoe is a giant sessile peritrich ciliated protozoa that possesses a contractile organelle called a spasmoneme. We report here on the molecular characterization and provide an opportunity to discuss the evolutionary relationships of the Z. arbuscula spasmin; spasmins belong to the calmodulin superfamily and are the major components of spasmoneme filaments. We analysed and obtained the whole sequence of the spasmin 1 gene and a partial sequence of the spasmin 2 gene. It is surprising that the sequence of spasmin 1 does not contain introns and encodes an open reading frame of 531 bp. It predicts a product of 177 amino acids with a calculated molecular mass of 19659 Da and a pI of 4.68. The amino acid sequence has two putative calcium-binding domains. One of them is a functional domain, as defined by the EF-hand consensus. The varieties of spasmins were revealed by comparison with amino acid components and molecular relationships of spasmin 1 protein and other spasmins. A comparison of the amino acid sequence between the Z. arbuscula spasmin and known centrins indicates that spasmins have a one residue deletion in the EF-hand domain-2 and four residue insertions in domain-4, as does the Vorticella spasmin. However, there are large variations in the amino acid sequence at domain-4 within spasmin 1, spasmin 2 and the Vorticella spasmin.

Amino Acid Motifs↗

Developmentally controlled genomic rearrangements in ciliated protozoa.

The ciliated protozoa undergo an extensive genome reorganization during the course of forming a transcriptionally active macronucleus. The process includes numerous chromosome fragmentation and DNA breakage and rejoining events. Recent work indicates that transposable elements play a role in the process.

Animals↗

Unexplored reservoirs of pathogenic bacteria: protozoa and biofilms.

In the natural, industrial, hospital and domestic environments, there are numerous phenotypes of pathogenic microorganisms, which vary considerably in chemical, physical and biological properties. A link exists between survival, resistance and virulence. In particular, surface-adherent biofilms and bacteria living within protozoa pose potential health problems that are unrecognized by conventional laboratory culture methods.

Animals↗

Targeting DHFR in parasitic protozoa.

Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.

Animals↗

Potential drug targets in cyst-wall biosynthesis by intestinal protozoa.

Given that resistance to antiprotozoal drugs exists and is likely to increase and given that currently no reliable treatments exist for some of these infections, efforts to find new targets for chemotherapy must be continued. In the case of cyst-forming pathogenic protozoa, one such target might be encystment pathways and cyst-wall assembly. Information is increasing on protozoan encystment and, as it does, we can begin to answer the question of whether targeting it for chemotherapy is a viable drug strategy. Currently, there are significant efforts to understand encystment in Giardia and Entamoeba, and potential targets are being discovered as work on their encystment mechanisms progress. We know with certainty now that Giardia and Entamoeba cyst walls contain unique proteins and polysaccharides which differ from those of their hosts and thus make them potentially interesting targets for a variety of chemotherapeutic attacks. Although we lack detailed information about the other protozoan cyst formers, enough evidence exists for Giardia and Entamoeba that it seems prudent to screen them with some of the antifungal drugs, especially those that target mannoproteins, chitin synthesis, and beta (1, 3) glucan synthesis to ascertain if they target elements in these protozoan pathways that are similar to those found in fungi.

Animals↗

Signaling of immune system cells by glycosylphosphatidylinositol (GPI) anchor and related structures derived from parasitic protozoa.

Glycosylphosphatidylinositol (GPI) anchor and glycoinositolphospholipid (GIPL) are abundant molecules present in the membrane of parasitic protozoa that are common etiologic agents of medical and veterinary diseases. Recent studies have documented the immunostimulatory/regulatory activity of protozoan-derived GPI-anchors and related structures. Among the bioactivity displayed by the protozoan-derived GPI-anchor is the ability to elicit the synthesis of pro-inflammatory cytokines as well as nitric oxide by host macrophages. In contrast, at high concentrations GIPL and lipophosphoglycan (LPG) derived from protozoan parasites suppress several functions of the host immune system. Additionally, the protozoan-derived GPI-anchor and GIPL have been shown to serve as targets for both specific B and NK-T lymphocyte responses. This information extends our knowledge about parasite molecules that stimulate/regulate the host immune system during protozoan infection. The identification of receptor(s) and signaling pathways triggered by these GPI-related glycolipids may provide new insights for the development of therapies that inhibit detrimental immune responses or potentiate beneficial immune responses observed during infection with protozoan parasites.

Animals↗

Ecto-ATPases in protozoa parasites: looking for a function.

The plasma membrane of cells contains enzymes whose active sites face the external medium rather than the cytoplasm. The activities of these enzymes, referred to as ecto-enzymes, can be measured using living cells. Cell membrane ecto-ATPases are integral membrane glycoproteins that are millimolar divalent cation-dependent, low specificity enzymes that hydrolyze all nucleoside triphosphates. Their physiological role is still unknown. However, several hypotheses have been suggested such as; (i). protection from cytolytic effects of extracellular ATP, (ii). regulation of ectokinase substrate concentration, (iii). termination of purinergic signaling, (iv). involvement in signal transduction, and (v). involvement in cellular adhesion. In this review, the biochemical properties and possible functions of the ecto-ATPases of different protozoa are summarized.

Adenosine Triphosphatases↗

Ecology of testate amoebae (Protozoa: Rhizopoda) on peatlands in western Russia with special attention to niche separation in closely related taxa.

Testate amoebae (Protozoa: Rhizopoda) are frequently used as indicators of past environmental changes, and the interpretation of fossil assemblages depends upon our knowledge of ecological affinities of taxa in modern environments. A variety of taxonomic approaches have been used in fossil studies, mostly involving grouping of closely related taxa. This paper presents data from peatlands in western Russia relating surface wetness parameters to species occurrence. Relationships between species abundance, water table depth and soil moisture are modelled using weighted averaging, and species niches are calculated as optima and tolerance for these parameters. Niche separation of closely related taxa is examined in detail and it is shown that there is often a gradient of hydrological preference within each group of taxa. Wet to dry gradients include those found in the Trigonopyxis arcula group (T. arcula var. major > T. arcula > T. minuta), the Assulina-Valkanovia group (A. seminulum > A. muscorum > V. elegans), and the Trinema lineare group (T. lineare var. truncatum/ T. lineare > T. lineare var. terricola), all of which are associated with a large to small size gradient. In addition, spined forms within the Euglypha and Placocista genera are shown to consistently occur in wetter habitats than glabrous forms or those with shorter spines. It is concluded that palaeoecological studies should attempt the lowest taxonomic divisions possible within these groups, to maximise the ecological indicator value of the assemblages recorded.

Amoeba↗

Modelling of microscale patch encounter by chemotactic protozoa.

A model of protozoan chemotaxis, based on the rate of change of chemoreceptor occupancy, was used to analyse the efficiency of chemotaxis in a variety of situations. Simulated swimming behaviour replicated patterns observed experimentally. These were classified into three forms of chemosensory behaviour; run-tumble, steered turning, and helical klinotaxis. All three could be simulated from a basic model of chemotaxis by modifying memory times and rotational velocities. In order to steer during helical klinotaxis, the cell must have a short term memory for responding to a signal within a fraction of the time period of the helix. Steered turning was identified as a form where cells react to negative changes in concentration by steering around the turn to swim back up the gradient. All 3 forms were quite effective for encountering targets within the response radius. A response to negative changes in concentration, experienced when the cell is moving away from a target, was found to be important in the absence of periodic changes in swimming direction. The frequency of patch encounter at a fixed density was calculated to be roughly proportional to swimming speed. On the basis of the model, cells are only able to sense point sources within a radius of a few mm. However, even a response radius of 1 mm is enough to increase encounter probability of otherwise minute targets by 2 orders of magnitude. The mean time for patch encounter was calculated to be an exponential function of the mean distance between patches. This results in a very sharp threshold at approximately 6 cm, above which they are not encountered by protozoa within time periods of several days.

Animals↗

Clonal variation of gene expression as a source of phenotypic diversity in parasitic protozoa.

Within a cellular clone, individual cells can express different members of a gene family. If the difference in expression is transmitted to daughter cells, 'phenotypic clones' are formed. Such clonal phenotypic variation has evolved independently in phylogenetically distant parasitic protozoa under similar selective pressure: the need for phenotypic diversity at several steps of their life cycle. Here, I review clonal phenotypic variation processes, outline their role in parasite biology and argue that clonal phenotypic variation is complementary to sexual reproduction as a source of phenotypic diversity.

Animals↗

Protein kinases as drug targets in parasitic protozoa.

The importance of protein kinases in cell signaling and cell cycle control has led to detailed structural and functional studies in various eukaryotes, and hence to the synthesis of specific chemical inhibitors for managing disease. Here, the current progress in applying developments from the wider protein kinase field to parasitic protozoa is reviewed. The availability of genome sequence data for several parasites has led to the identification of many protein kinases. Reverse genetics studies, including gene knockout and 'chemical genetics', can help to define the roles of the protein kinases and validate them as drug targets. In addition, screening chemical libraries with active recombinant protein kinases can identify lead compounds for drug design.

Animals↗

The clonal theory of parasitic protozoa: 12 years on.

The question of population structure in parasitic protozoa has recently gained a renewed topicality with significant contributions on medically important pathogens, such as Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. The proposals that initiated this debate are reviewed here and the subsequent developments of the clonal theory, in light of recent contributions, are examined.

Animals↗

Frontiers in research on parasitic protozoa.

Frontiers in research on parasitic protozoa was the theme of the Autumn Symposium of the British Section of the Society of Protozoologists, held 2 September 2002, in London, UK.

Animals↗

Proteinases of Leishmania mexicana and other flagellate protozoa.

The amastigote form of the human pathogen Leishmania mexicana contains high proteinase activity, some 20 times greater than that in the promastigote form and macrophages and appreciably higher than the activity in other flagellate protozoa. The main amastigote enzymes are soluble, whereas those of the promastigote are particulate, and have inhibitor sensitivities characteristic of cysteine proteinases. The very high soluble proteinase activity of L. mexicana amastigotes may be a primary factor in the survival and growth of this mammalian stage in its potentially degradative intracellular habitat.

Animals↗

Novel biochemical pathways in parasitic protozoa.

Throughout evolution, enzymes and their metabolites have been highly conserved. Parasites are no exception to this and differ most markedly by the absence of metabolic pathways that are present in the mammalian host. In general, parasites are metabolically lazy and rely on the metabolism of the host both for a supply of prefabricated components such as purines, fatty acids, sterols and amino acids and for the removal of end-products. Nonetheless, parasites are metabolically highly sophisticated in that (1) they retain the genetic capacity to induce many pathways, when needed, and (2) they have developed complex mechanisms for their survival in the host. Certain unique features of the metabolism of trypanosomes, leishmania, malaria and anaerobic protozoa will be discussed. This will include (1) glycolysis and electron transport with reference to the unique organelles: the glycosome and the hydrogenosome, (2) purine salvage, pyrimidine biosynthesis and folic acid metabolism and (3) polyamine and thiol metabolism with special reference to the role of the unique metabolite of trypanosomes and leishmanias, trypanothione.

Animals↗