Surface-expressed enolases of Plasmodium and other pathogens

Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed.

¿La hemozoína, presente y futuro? / ¿Hemozoin present and future

La malaria es una enfermedad causada por parásitos del género Plasmodium estos parásitos tienen un ciclo intraeritocítico en el hospedador vertevrado. En el glóbulo rojo, el parásito ingiere la hemoglobina, obteniendo aminácidos y formando hemozoína. La hemozoína es un un material microcristalino oscuro, de color marrón amarillento, insoluble en agua, no tóxico, producido en la vacuola parasitófora del Plasmodium; este compuesto producido por el Plasmodium carece de la toxicidad que tiene el grupo hemo para el parásito. Asimismo se ha evidenciado que la hemozoína es una sustancia inmuno moduladora que tiene diversos efectos, como mediar la activación y migración de neutrófilos, incrementar la producción de óxido nítrico, inducir la activación de mataloproteínas 9, inducir la secreción de diferentes mediadores proinflamatorios, alterar las funciones de los monocitos y macrófagos humanos, tales como el estallido oxidativo, eliminación de bacterias, presentación de antígenos y la habilidad de diferenciarse a células dendríticas funcionales; por lo que la hemozína tiene efectos duales, tanto activadores como supresores de la respuesta inmune. Asimismo, la hemozoína es unblanco terapéutico potente, ya que los fármacos que inhiban su formación provocan toxicidad al parasíto e incluso la muerte del mismo.

Malaria is a disease caused by parasites of the genus Plasmodium. These parasites have intraerythrocytic cycle in the vertbrate host. In the red cell, the parasite ingests hemoglobin, obtaining amino acids and formin hemozoin. The microcrystaline material hemozoin is a dark, yellowish brown, insoluble in water, nontoxic, produced in the Plasmodium parasitophorous vacuole, this compound produced by Plasmodiun lacks the toxicity that has heme to the parasite. It has also been shown that hemozoin is an immune modulating substance that has different ffects, mediating the neutrophils activation and migration, increased nitric oxide production, induce activation of metallproteinase-9, induce the secretion of various proinflammatory mediators, alter the funcions of human monocytes and macrophages such as oxidative burst, removing bacteria, antigen presentation and the ability to differentiate into functional dendritic cells, so the hemozoin has dual effects, both activators and suppressors of the immune response. Also, the hemozoin is a potent therapeutic target, since rugs that inhibit their formation causes toxicity to the parasite and even death itself.

Evaluation of diagnostic methods of re-emerging malaria in Korean patients

Malaria is one of the most important parasitic diseases especially in tropical areas. Over 300 million people are affected and the condition causes 1-3 million deaths each year. It is transmitted by the bite of infected Anopheles mosquitoes. Although Korea was declared to be free of Malaria by the WHO in 1979, malaria re-emergence has been apparent since 1993 amongst soldiers located near the De-Militarized Zone (DMZ) in the northern part of the country. Conventional microscopic examination of thin and thick blood films demonstrates the presence of the parasite and thus this method has been used to confirm the diagnosis of malaria, but it is a labor-intensive procedure and relies upon subjective interpretation. To overcome these limitations, fast and reliable methods for malaria detection have been recently introduced. In this study, we compared three kinds of antibody detection kits and one biochemical test kit that determines the presence of Plasmodium lactate dehydrogenase (pLDH) with conventional peripheral blood smears. The antibody detection methods examined were, two rapid test pack format methods and a single microplate format enzyme-linked immunosorbent assay (ELISA) kit, as manufactured by Korean companies. The sensitivities of the three commercial antibody detection kits in the early stage of malaria were 70.8%, 77.4%, and 63.6%, their corresponding specificities 90.5%, 91.8%, and 80.9%, and their accuracies 87.6%, 87.0%, and 76.7%. The sensitivity and specificity of the pLDH assay were 100% apiece and the results were in 100% concordance with the microscopy of thick blood films. Thus, the pLDH assay may be used as an alternative for conventional microscopic blood film examination, especially in emergency situations when prompt treatment is necessary.

Fosforilación en células eucarióticas: papel de fosfatasas y quinasas en la biología, patogenia y control de protozoosis tisulares y sanguíneas / Phosphorylation in eukaryotic cells: role of phosphatases and kinases in biology, pathogenesis and control of intracellular and bloodstream protozoa

Cells respond to environmental or cellular changes, rapidly switching protein activities from one state to another. In eukaryotes, a way to achieve these changes is through protein phosphorylation cycles, involving independent protein kinase and protein phosphatase activities. Current evidences show that phosphatases and kinases are also involved in the molecular basis of immune response and in diseases such as diabetes obesity and Alzheimer. In protozoan parasites like Trypanosoma and Leishmania, several kinases and phosphatases have been identified, many of them have been cloned but in several cases their biological role remains undetermined. In this review, the state-of-the art is summarized and the role of phosphatases and kinases in biological phenomena such as remodeling, invasion and pathogenic capacity of protozoan parasites is described. The real chance to use these components of signal transduction pathways as target for chemotherapeutic intervention is also discussed

Resolution of enzyme bands of Plasmodium knowlesi as a function of substrate concentration.

An extra band of isoenzyme lactate dehydrogenase (LDH) was obtained in case of Plasmodium knowlesi free parasite as compared to normal monkey blood. This extra band could be resolved due to the decreasing amount of substrate concentration. Agarose electrophoresis technique was used to separate the isoenzyme bands.