Binding of Malaria Parasites to Host cells

“MALARIA”

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

• The life cycle of Plasmodium is
extraordinarily complex

Life cycle of Plasmodium

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

annister 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

p://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 researchUNDP, 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/m 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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