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Binding of Malaria Parasites to Host cells

EM of a plasmodium       Advanced cell biology II, class presentation
                                                      Kedar Ghimire,
                                                         April 5, 2006
 Why do we need to concern about Malaria and the
 tiny mosquito?

• Infects 200-300 million people every year!
• Kills 1-3 million people!!!
• Kills one child every 30 seconds!!!!!
      Brief History of Malaria
• Originated in Africa
• In 1898, Ronald Ross discovered
  plasmodium in Anopheles mosquitoes
• In past, common in the whole world and
  mostly in Rome, name derived from the
  Italian (male-aria)
            Malarial parasite

• Caused by four species of Plasmodium
• Transmitted by any of 60 species of
  Anopheles among 400 species
• Plasmodium Falciparum- the most
  dangerous species and luckily ,the
  intensely studied one
       Life cycle of Plasmodium
• The life cycle of Plasmodium is
 extraordinarily complex

            Life cycle of Plasmodium Falciparum
Binding of parasite to mosquito cells
•   Parasites tend to attack specific tissues of mosquito
•   Hypothesis, specific ligands- specific receptors binding
•   Specific recognition event, evidence is there to support it.
•   Sporozoites have surface protein called CS protein and
•   The protein Saglin- a salivary-gland receptor for parasites
    (its ability to bind the sporozoite surface protein TRAP
•   Laminins expressed in the midgut epithelial cells thought
    to bind malaria parasites
                                Merozoite invasion of red blood cells

            Apical adhesion

Bannister et al., 1975, Parasitology, 71, 483-491
Binding of parasite to mammalian
host cells
• Plasmodium sporozoites successfully
  invades liver
• They also express a surface protein CS
  and TRAP(SSP2)- sporozoite ligands,
  (STARP, LSA-3)
• CS binds to hepatocyte microvilli on HSPG
  and CSPG
      Entry into red blood cells

Change in Rbc‘s shape: knob formation
  Possible explanation for binding of sporozoites to hepatocytes
Plasmodium and problems for immune system

• Toxins released during growth, reproduction or
    rupture of red blood cells
•   Malaria parasites hide from immune system
    (Nature, 2005)
• Plasmodium falciparum constantly changes the
    appearance of a protein pfEMP1 it deposits on
    infected RBCs
•   They mainly damage Red blood cells
Prospects for Anti malarial vaccines, drugs,
           genetic methods????

•   Anti-malarial vaccines- not yet
•   Chloroquine, mefloquine etc- resistance and side effects
•   Genetically engineered mosquitoes
•   Organisations funding the malarial research- UNDP,
    WHO, The Wellcome trust, Gates foundation etc

• Sultan AA, Molecular mechanisms of malaria sporozoite motility and invasion of host
    cells,1999, Int Microbiol
•   Cerami C. et al (1992), The basolateral domain of the hepatocyte plasma membrane
    bears receptors for the circumsporozoite protein, Cell, Cell press
•   Kappe S. et al (2001), Exploring the transcriptome of the malaria sporozoite stage ,
• Fidock DA, Bottius E, Brahimi K, Moelans II, Aikawa M, Konings RN, Certa U, Olafsson P,
    Kaidoh T, Asavanich A, et al.,1994, Mol Biochem parasitol
•   Daubersies P, Thomas AW, Millet P, Brahimi K, Langermans JA, Ollomo B, BenMohamed
    L, Slierendregt B, Eling W, Van Belkum A, Dubreuil G, Meis JF, Guerin-Marchand C,
    Cayphas S, Cohen J, Gras-Masse H, Druilhe al, 2000, Nature-Medicine
•   Consuelo Pinzon-Ortiz. Et al, 2005, The binding of the circumsporozoite protein
    to cell surface proteoglycans is required for plasmodium sporozoite
    attachment to target cells, J. Biol. Chem

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