Multidrug resistance and ABC transporters in parasitic protozoa

Drug resistance is an important problem in parasitic protozoa. We review here the role of ABC transporters in drug resistance in parasites. We have concentrated on gene and gene products for which there is a strong evidence for their role in resistance.     

Viruses of parasitic protozoa

Associations are increasingly recognized between parasitic protozoa and smaller organisms such as bacteria (see Parasitology Today 1, 143), and viruses. Their revelation, originally by ultrastructural studies, may now be indicated by observations of 'rogue bands' on gel electrophoresis of parasite nucleic acids. The origins and roles of parasite 'parasites' are still uncertain, but, as Michael Miles suggests here, they may prove of particular importance as agents to introduce genes for important immunogens into non-pathogenic protozoa for vaccine delivery.     

Viruses of parasitic protozoa

Recently, specific viruses have been identified among the parasitic protozoa Trichomonas vaginalis, Giardia lamblia, Leishmania braziliensis, the Eimeria spp and the Babesia spp. These viruses share many features: they are all RNA viruses and most, if not all, doublestranded (ds) RNA viruses with nonsegmented genomes ranging between 5 and 7 kilobases (kb); they are spherical or icosahedral with an average diameter of 30-40 nm. The giardiavirus is one of the best characterized and can infect virus free G. lamblia trophozoites in its freed, pure form. The replicative intermediate of the giardiavirus genome has been isolated from infected cells, and can be introduced into G. lamblia by electroporation to produce giardiavirus, thus raising the possibility of its being used as a specific genetic transfection vector for the parasite.     

Encystation in parasitic protozoa

Giardia and Entamoeba parasites encase themselves in a carbohydrate-rich cyst for travel from host to host. Both parasites upregulate their Golgi apparatus during this process, yielding organelles that are now found to be similar to those of higher eukaryotes. In fact, unusual enzymes and structural proteins used for cyst wall synthesis, the complexity of the secretory pathways used to transport materials to the developing cyst walls, as well as unexpected mechanisms of gene regulation and parasite-host and parasite-parasite information exchange, are revealing a high level of sophistication in these organisms that occupy low branch points in the eukaryotic lineage.     

Glycoconjugate structures of parasitic protozoa

Glycoconjugates are abundant and ubiquitious on the surface of many protozoan parasites. Their tremendous diversity has implicated their critical importance in the life cycle of these organisms. This review highlights our current knowledge of the major glycoconjugates, with particular emphasis on their structures, of representative protozoan parasites, including Leishmania, Trypanosoma, Giardia, Plasmodia, and others.     

Cysteine proteinases of parasitic protozoa

Proteinases are involved with many processes in living organisms. In recent years, there has been increasing interest in elucidating the functions the enzymes perform in parasites. These studies have revealed that one class of proteinases, the cysteine proteinases, predominates in many parasitic protozoa. In this article Mick North, Jeremy Mottram and Graham Coombs review what is known about the cysteine proteinases of parasitic protozoa and discuss the approaches being pursued in attempts to design antiparasite drugs based on inhibitors or substrates of these enzymes.     

Iron acquisition by parasitic protozoa

The efficient uptake of iron by microorganisms is essential for their survival. Mammalian hosts possess elaborate means of sequestering their iron stores to protect themselves against invading pathogens. In this review, Mary Wilson and Bradley Britigan summarize mechanisms by which bacteria and protozoa effectively scavenge iron from their hosts during infection, as well as the potential and proven effects of these mechanisms on microbial virulence.     

Nucleoside transporters in absorptive epithelia

There are two families of nucleoside transporters, concentrative (termed CNTs) and equilibrative (called ENTs). The members of both families mediate the transmembrane transport of natural nucleosides and some drugs whose structure is based on nucleosides. CNT transporters show a high affinity for their natural substrates (with Km values in the low micromolar range) and are substrate selective. In contrast, ENT transporters show lower affinity and are more permissive regarding the substrates they accept. Both types of transporters are tightly regulated in all cell types studied so far, both by endocrine and growth factors and by substrate availability. The degree of cell differentiation and the proliferation status of a cell also affect the pattern of expressed transporters. Although the presence of both types of transporters in the cells of absortive epithelia suggested the possibility of a transepithelial flux of nucleosides, their exact localization in the different plasma membrane domains of epithelial cells had not been demonstrated until recently. Concentrative transporters are found in the apical membrane while equlibrative transporters are located in the basolateral membrane, thus strengthening the hypothesis of a transepithelial flux of nucleosides.     

Developmental processes in parasitic protozoa

The present paper gives an outline summarizing the ultrastructural features of important developmental processes of protozoan parasites. Especially mechanisms of reproduction and self-protection are described and will be comparatively illustrated during the lecture.     

Repetitive elements in parasitic protozoa

A recent paper published in BMC Genomics suggests that retrotransposition may be active in the human gut parasite Entamoeba histolytica. This adds to our knowledge of the various types of repetitive elements in parasitic protists and the potential influence of such elements on pathogenicity.     

Intermediary metabolism in parasitic protozoa

Recent advances in our knowledge of the intermediary metabolism of parasitic protozoa are reviewed and the implications of the findings to our understanding of how protozoan parasites are adapted to their environment are discussed.     

Niche metabolism in parasitic protozoa

Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generated in silico has been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism.