Protozoan Parasites
Protozoan parasites are a major threat to human health with millions of fatalities worldwide especially in nonindustrialized countries. Although there are hundreds of parasitic protozoa with different life cycles, reproductive processes and nutritional needs, to maintain the focus on AQP gene expression, a select few will be discussed briefly to provide a sample of their behavior as health hazards in developing nations. Formerly known as sporozoa, this Apicomplexa protozoa is one of the most important parasitic phyla.[49] Currently there is an estimate of 300-500 million cases with more than 2 million deaths annually due to malaria caused by P. falciparum.[50]
Apicomoplexa are unicellular parasitic protists with no locomotory organelles (flagella, pseudopods or cilia); however, some species possess motile structures, such as flagella or pseudopods, only in certain gamete stages. They are also characterized by a unique organelle called an apical complex for which they are named Apicomplexa. Depending on the species, sporogony may or may not occur in the human or animal host. They are spore-forming (hence the old name sporozoa), and exclusively parasites of humans and animals.
Apicomplexa have complex life cycles involving both asexual and sexual reproduction although the mechanism that regulates this process is unknown.[51] The parasite infects its host then starts dividing to produce sporozoites that enter the host's cells. Multiple parasitic cell divisions within the host's cells destroy the cell causing the cell to rupture and release merozoites, which then invade new cells within the host. This cyclic process continues several times, damaging major organs in the process, until gamonts are produced that form gametes. Gametes fuse to produce a zygote that develops into an oocyte in the Apicomplexa.
The growth in the number of severely immunocompromised individuals as a result of the AIDS epidemic, cancer chemotherapy and organ transplants has been paralleled both by the increasing prevalence of opportunistic infections and by greater recognition of the disease-causing potential of various other protozoan parasites, such as C. parvum, Cyclospora cayetanensis and Microsporidia, as human pathogens. Cryptosporidium remains a pathogen of both immunosuppressed (i.e., AIDS) and immunocompetent individuals, the latter associated with water outbreaks. Other members such as Toxoplasma gondii (toxoplasmosis), Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas' disease), and Leishmania species (leishmaniasis) are major health threats to millions of people worldwide. The association between socioeconomic status, rapid spread of infections and drug-resistant strains has worsened the conditions of those who are victims of these parasites. These factors have caused crises in those countries where the infections have spread.[43] Many of these parasitic species are known worldwide, such as Cryptosporidium sp. considered one of the most common pathogens throughout the world and once believed to be the pathogen of immunocompromised persons. This was disproved after a number of waterborne outbreaks occurred[52,53] and frequent cases in immunocompetent individuals were recorded.[54] The widely distributed and studied species of Apicomplexa Toxoplasma is T. gondii, an intracellular coccidian parasite that is transferred to humans through felines in cat litter or in sand boxes.[55]T. gondii has produced infection and sporadic major outbreaks.[56] Currently, there is no cure for many of these parasitic infections. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites.[57] Since the publication of the genome of P. falciparum, the number of published complete parasite genomes has increased dramatically.[14,44,45,58,59]
The Apicomplexan plastid, known as the apicoplast, is a membranous organelle with a possible function in lipid synthesis and maintenance of the organism's survival. With limited genetic resources, Apicomplexan parasites share many metabolic pathways with their hosts. This situation made finding therapeutic targets problematic since agents that would harm the parasite would have similar effects on the human host. These shared metabolic pathways also make it difficult to develop effective vaccines or treatments against parasites underscoring the need for novel targeting methods to be developed. Recent sequencing of many Apicomplexa genomes, and the availability of these genome sequences, provides a new opportunity for learning more about Apicomplexa evolution, biochemical pathways and, above all, developing new drugs. IMPs, at the interface between the parasite and its host, are a particularly promising target. These genes are highly optimized and fulfill vital roles for the parasitic organism. Among such genes are the AQPs,[3] which are considered potential candidates for anti-parasitic drug development for several reasons: the small number of exposed proteins is either immune stealth or masked or both at different stages of maturity. AQPs are significant in helping the parasite cope with the osmotic stress during transmission between hosts, and within the host's inner organs. Moreover, parasites are very dependent on their transporter proteins in passing nutrients in and waste materials out.[60,61]
Expert Rev Proteomics. 2009;6(2):199-211. © 2009 Expert Reviews Ltd.
Cite this: Protozoan Parasite Aquaporins - Medscape - Apr 01, 2009.
