scholarly journals Molecular Dynamics of Mosquito-Plasmodium vivax Interaction: A Smart Strategy of Parasitism

2021 ◽  
Author(s):  
Charu Chauhan ◽  
Sanjay Tevatiya ◽  
Seena Kumari ◽  
Punita Sharma ◽  
Jyoti Rani ◽  
...  

Parallel to Plasmodium falciparum, P. vivax is a fast emerging challenge to control malaria in South-East Asia regions. Owing to unique biological differences such as the preference for invading reticulocytes, early maturation of sexual stages during the infection, the formation of hypnozoites, unavailability of in-vitro culture, the molecular relation of P. vivax development inside the mosquito host is poorly known. In this chapter, we briefly provide a basic overview of Mosquito-Plasmodium interaction and update current knowledge of tissue-specific viz. midgut, hemocyte, and salivary glands- molecular dynamics of Plasmodium vivax interaction during its developmental transformation inside the mosquito host, in specific.




mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Catherine J. Mitran ◽  
Angie Mena ◽  
Sedami Gnidehou ◽  
Shanna Banman ◽  
Eliana Arango ◽  
...  

ABSTRACT Many pathogens evolve extensive genetic variation in virulence proteins as a strategy to evade host immunity. This poses a significant challenge for the host to develop broadly neutralizing antibodies. In Plasmodium falciparum, we show that a mechanism to circumvent this challenge is to elicit antibodies to cryptic epitopes that are not under immune pressure. We previously discovered that antibodies to the Plasmodium vivax invasion protein, PvDBP, cross-react with P. falciparum VAR2CSA, a distantly related virulence factor that mediates placental malaria. Here, we describe the molecular mechanism underlying this cross-species immunity. We identified an epitope in subdomain 1 (SD1) within the Duffy binding-like (DBL) domain of PvDBP that gives rise to cross-reactive antibodies to VAR2CSA and show that human antibodies affinity purified against a synthetic SD1 peptide block parasite adhesion to chondroitin sulfate A (CSA) in vitro. The epitope in SD1 is subdominant and highly conserved in PvDBP, and in turn, SD1 antibodies target cryptic epitopes in P. falciparum VAR2CSA. The epitopes in VAR2CSA recognized by vivax-derived SD1 antibodies (of human and mouse origin) are distinct from those recognized by VAR2CSA immune serum. We mapped two peptides in the DBL5ε domain of VAR2CSA that are recognized by SD1 antibodies. Both peptides map to regions outside the immunodominant sites, and antibodies to these peptides are not elicited following immunization with VAR2CSA or natural infection with P. falciparum in pregnancy, consistent with the cryptic nature of these target epitopes. IMPORTANCE In this work, we describe a molecular mechanism of heterologous immunity between two distant species of Plasmodium. Our results suggest a mechanism that subverts the classic parasite strategy of presenting highly polymorphic epitopes in surface antigens to evade immunity to that parasite. This alternative immune pathway can be exploited to protect pregnant women from falciparum placental malaria by designing vaccines to cryptic epitopes that elicit broadly inhibitory antibodies against variant parasite strains.



2010 ◽  
Vol 54 (12) ◽  
pp. 5146-5150 ◽  
Author(s):  
R. N. Price ◽  
J. Marfurt ◽  
F. Chalfein ◽  
E. Kenangalem ◽  
K. A. Piera ◽  
...  

ABSTRACT Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The in vitro antimalarial susceptibility of pyronaridine was assessed in multidrug-resistant P. vivax (n = 99) and P. falciparum (n = 90) isolates from Papua, Indonesia, using a schizont maturation assay. The median 50% inhibitory concentration (IC50) of pyronaridine was 1.92 nM (range, 0.24 to 13.8 nM) against P. falciparum and 2.58 nM (range, 0.13 to 43.6 nM) against P. vivax, with in vitro susceptibility correlating significantly with chloroquine, amodiaquine, and piperaquine (rs [Spearman's rank correlation coefficient] = 0.45 to 0.62; P < 0.001). P. falciparum parasites initially at trophozoite stage had higher IC50s of pyronaridine than those exposed at the ring stage (8.9 nM [range, 0.6 to 8.9 nM] versus 1.6 nM [range, 0.6 to 8.9 nM], respectively; P = 0.015), although this did not reach significance for P. vivax (4.7 nM [range, 1.4 to 18.7 nM] versus 2.5 nM [range, 1.4 to 15.6 nM], respectively; P = 0.085). The excellent in vitro efficacy of pyronaridine against both chloroquine-resistant P. vivax and P. falciparum highlights the suitability of the drug as a novel partner for artemisinin-based combination therapy in regions where the two species are coendemic.



2007 ◽  
Vol 156 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Liselotte Yimga Djapa ◽  
Leonardo K. Basco ◽  
Ruth Zelikson ◽  
Andre Rosowsky ◽  
Joseph Allico Djaman ◽  
...  


Author(s):  
Alida Marcela Gómez Rodríguez ◽  
Laura Esperanza Cuy-Chaparro ◽  
Anny Jineth Camargo Marcipe

Introducción. Comprender la función de antígenos de Plasmodium spp., involucrados en invasión a células hospederas es necesario para diseñar vacunas. Diferentes estudios han generado proteínas recombinantes utilizando sistemas de expresión heterólogos, obteniendo moléculas semejantes a las nativas. Estos avances son fundamentales para desarrollar estrategias que bloqueen la infección de estos patógenos. Objetivo. Describir las características y aspectos metodológicos más importantes de sistemas de expresión de proteínas recombinantes en estudios funcionales de Plasmodium spp. Metodoogía. Revisión descriptiva de estudios publicados en PubMed, Science Direct, Embase y MedLine. Criterios de inclusión: trabajos publicados entre el 2010 y 2020 que incluyeran sistemas recombinantes en células de Escherichia coli, de mamífero y libre de células, para estudios funcionales de antígenos de Plasmodium falciparum y Plasmodium vivax. Se revisaron 70 artículos originales, 58 cumplieron con los criterios establecidos y 12 utilizaron otros sistemas heterólogos diferentes a los analizados en este estudio.    Resultados. Obtener proteínas recombinantes mediante sistema procariota, de mayor rendimiento y bajo costo, ha permitido estudios funcionales de un número importante de antígenos. Los sistemas con células de mamífero y libre de células, que permiten modificaciones pos-traduccionales y plegamiento adecuado de moléculas, se usan para producir librerías de antígenos con estructura conformacional similar a la nativa.  Conclusión. Estudio de antígenos de Plasmodium spp. implicados en infección y desarrollo en células diana, requiere adecuada selección del método de producción recombinante. El refinamiento de procesos de expresión en sistemas procariotas, eucariotas e in vitro, mediante ingeniería genética y cultivo celular, permitirá mejores rendimientos y menor costo.



1912 ◽  
Vol 16 (4) ◽  
pp. 567-579 ◽  
Author(s):  
C. C. Bass ◽  
Foster M. Johns

The asexual cycle of Plasmodium vivax and Plasmodium falciparum has been cultivated in vitro in human blood. The parasites have been grown also in red blood cells in the presence of Locke's solution, free of calcium chlorid and in the presence of ascitic fluid. The parasites grow within red blood cells and there is no evidence that they can be grown outside of these cells. The parasites are destroyed in a very few minutes in vitro by normal human serum or by all modifications of serum that we have tested. This fact, together with numerous observations of parasites in all stages of growth apparently within red cells, renders untenable the idea of extracorpuscular development. Leucocytes phagocytize and destroy malarial plasmodia growing in vitro only when the parasites escape from their red blood cell capsule or when the latter is perforated or becomes permeable. Successive generations of Plasmodium vivax and Plasmodium falciparum have been cultivated in vitro by removing the leucocytes from the culture and by transplanting to fresh red blood cells and serum at proper intervals. The asexual cycle of Plasmodium vivax and Plasmodium falciparum cultivated in vitro does not differ from the same cycle growing in vivo. The sexual cycle has not been cultivated, though we have obtained some evidence of the possibility of its accomplishment. There can no longer be any doubt that Plasmodium vivax and Plasmodium falciparum are separate and distinct species. When grown in an identical culture medium and under exactly the same conditions they remain distinct. In twenty-nine cultures of æstivo-autumnal parasites many forms and sizes have been observed, so that evidence is supplied of the occurrence of different varieties of ætivo-autumnal malarial plasmodia. The so called tertian ætivo-autumnal variety may be seen at the proper stage in all cultures grown from merozoites. The form and appearance of the same culture of plasmodia may vary greatly under different conditions which are not necessarily destructive to the parasites. Their generation period may vary from thirty hours (ætivo-autumnal) to four days (tertian), as a result of variation in the temperature at which they were cultivated. Sexual parasites grow in the cultures and are more resistant to unfavorable conditions than schizonts, often living several days after the latter die out. Forms suggesting parthenogenesis have been observed.



2006 ◽  
Vol 50 (11) ◽  
pp. 3631-3637 ◽  
Author(s):  
Sasinee Bunyarataphan ◽  
Ubolsree Leartsakulpanich ◽  
Supannee Taweechai ◽  
Bongkoch Tarnchompoo ◽  
Sumalee Kamchonwongpaisan ◽  
...  

ABSTRACT Pyrimethamine analogs were examined as potential agents against vivax malaria using a bacterial surrogate system carrying Plasmodium vivax dihydrofolate reductase-thymidylate synthase (PvDHFR-TS), in which the PvDHFR complemented chemically knocked out host dihydrofolate reductase. The system was initially tested with P. falciparum dihydrofolate reductase-thymidylate synthase and was found to have good correlation with the parasite-based system. The 50% inhibitory concentrations derived from PvDHFR-TS-dependent bacteria were correlated with their corresponding inhibition constants (Ki ) from an enzyme inhibition assay, pointing to the likelihood that the potent enzyme inhibitors will also have potent antimalarial activities. Active compounds against both wild-type and S58R S117N (SP21) double-mutant P. vivax include analogs with structures which can avert a steric clash with the asparagine (S117N) side chain of the mutant, similar to those found for homologous Plasmodium falciparum mutants, raising the possibility that the same compounds can be developed against both types of antifolate-resistant malaria. This rapid and convenient drug screening system should be useful for development of new antifolates against P. vivax, for which a continuous culture system is not yet available.



2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Setthakit Chitsanoor ◽  
Sangdao Somsri ◽  
Panyu Panburana ◽  
Mathirut Mungthin ◽  
Ratawan Ubalee ◽  
...  


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