Malaria binding of malaria parasites to host cells
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“MALARIA” Binding of Malaria Parasites to Host cells. Advanced cell biology II, class presentation Kedar Ghimire, April 5, 2006. EM of a plasmodium. Why do we need to concern about Malaria and the tiny mosquito?. Infects 200-300 million people every year! Kills 1-3 million people!!!

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“MALARIA” Binding of Malaria Parasites to Host cells

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“MALARIA”Binding of Malaria Parasites to Host cells

Advanced cell biology II, class presentation

Kedar Ghimire,

April 5, 2006

EM of a plasmodium


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 TRAP.

  • 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


Change in Rbc‘s shape: knob formation

Entry into red blood cells


Possible explanation for binding of sporozoites to hepatocytes

http://trc.ucdavis.edu/mjguinan/apc100/modules/Digestive/mammal/liver5/liver.html


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


THANK YOU ALL FOR YOUR KIND ATTENTION,

QUESTIONS?

References

  • 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 , PNAS

  • 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 P.et al, 2000, Nature-Medicine

  • http://www.rph.wa.gov.au/labs/haem/malaria/history.html

  • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/J/Junctions.html

  • http://news.bbc.co.uk/2/hi/health/4419835.stm

  • 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

  • http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003/Lafontaine/malariawebpage.htm

  • http://en.wikipedia.org/wiki/Chloroquine

  • http://www.wellcome.ac.uk/en/malaria/TheParasite/pfantv1.html

  • http://www.anobase.org/embo_meeting/2005/abstracts/JacobsLorena.pdf


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