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“MALARIA”

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 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 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/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