PARASITES

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PARASITES
Protozoa(single cells)
Helminths(worms)
malaria,trypanosomes, ameba, etc.
Nematodes(roundworms)
ascaris, strongyloides, etc.
Platyhelminths(flatworms)
Cestodes(tapeworms)
Trematodes(flukes)
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How are parasites transmitted?

• Orally like bacteria from contaminated water or
  food(giardia, Entamoeba)
• Direct infection(strongyloides, hookworm,
  schistosomes through skin)
• By insect vectors--bloodsucking bugs, flies,
  mosquitos(malaria, trypanosomes, filarid worms)

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Giardia lamblia
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Cyst
Emerging trophozoite
Feely etal J.Parsitol,77441
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Putative virulence factors for Entamoeba
histolytica

• Adhesion molecules(lectin) that mediate binding
  to epithelial cell surface
• Contact-dependent amebapore that lyses host
  cells
• Proteases for degrading cell-cell contacts and
  extracellular matrix

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Amebapore subunit and complex
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Virulence and species of Entamoeba

• Only 10 of infections lead to serious intestinal
  damage or metastases
• Yet all Entamoeba are morphologically identical
• Genomic differences between pathogenic and
  non-pathogenic isolates-2 species?

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Why are there pathogenic ameba?

• Pathogenic ameba harm their host and invasion is
  a lifecycle deadend.

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How are parasites transmitted?

• Orally like bacteria from contaminated water or
  food(giardia, Entamoeba)
• Direct infection(strongyloides, hookworm,
  schistosomes through skin)
• By insect vectors--bloodsucking bugs, flies,
  mosquitos(malaria, trypanosomes, filarid worms)

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Shistosomatium douthitti(Trichobilharzia would
have bird host)gtgtgtswimmers itch
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Cercaria(invasive aquatic larva)
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The evolution of parasitism clues from host
finding and organ specific gene expression in
nematodes
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Parasite(H. contortus) nematode promoter for gut
protease correctly drives reporter expression in
C.elegansBritton et al Mol Biochem Parasit
103171, 1999
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Chemosensation in strongyloides
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How are parasites transmitted?

• Orally like bacteria from contaminated water or
  food(giardia, Entamoeba)
• Direct infection(strongyloides, hookworm,
  schistosomes through skin)
• By insect vectors--bloodsucking bugs, flies,
  mosquitos(malaria, trypanosomes, filarid worms)

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Chagas Disease(Trypanosoma cruzi)
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Trypanosoma cruzi
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OK, I see how you get in but how do you hitch a
ride out?
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Microfilaria on the move
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Mazzotti reaction following treatment of
onchocerciasis
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Why dont we have parasite vaccines?

• Parasites evade the immune response
• Parasites exploit the immune response
• Maybe going after the wrong targets

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How do parasites evade the immune response?

• Hide inside cells(malaria, leishmania, T.cruzi)
• Alter immune cell function(leishmania)
• Surface camouflage(schistosomes)
• Change surface coat(trypanosomes)

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Malaria parasites
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The Malaria Problem

• Infects approximately 300-500 million people
  each year
• 2-3 million people die each year
• Four plasmodial species infect humans
• Plasmodium falciparum is most lethal parasite
• Drug Resistance is rising against the most common
  antimalarials

www.dpd.cdc.gov
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Two mechanisms of protozoan parasite cell
invasion.Toxoplasma(L)and malaria use active
invasion/T.cruzi recruits lysosomes
T.cruzi
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Ultrastructure- Malaria Life Cycle
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Model for Merozoite Invasion
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How do parasites evade the immune response?

• Hide inside cells(malaria, leishmania, T.cruzi)
• Alter immune cell function(leishmania)
• Surface camouflage(schistosomes)
• Change surface coat(trypanosomes)

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Ross, R. Thompson, D. A case of sleeping
sickness studied by precise enumerative methods.
Regular periodic increase in the parasites
disclosed. Proc. Royal Soc London 1910
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T.brucei infection marked by waves of fever and
parasites
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Trypanosome antigenic variation-changing the
VSG(variant surface glycoprotein coat)

• 1000 chromosome internal and another 100 mini
  chromosome VSG genes
• Rearrange gene to be expressed by conversion or
  reciprocal recombination to an expression
  site(ES)
• Choose one of 20 ES by segregation to a specific
  nuclear body where RNA polymerase I (not II!)?

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How the trypanosome changes its coatP.Borst,
Cell, 109, 5-8, 2002
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