Introduction to Protozoan parasites
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....much of which is parasiticThe majority of eukaryotic life is protozoan...
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Kinetoplast - defining feature of all kinetoplastids
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Kinetoplast - defining feature of all kinetoplastids
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Kinetoplast - defining feature of all kinetoplastids
kinetoplastids
Lukes, Euk. Cell, 2002
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
kinetoplastids
Lukes, Euk. Cell, 2002
Hajduk, FASEB, 1993
Kinetoplast - defining feature of all kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of alveolates
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of alveolates
The Inner Membrane Complex (IMC) underlies the parasite plasma membrane
6IMC: flattened vesicles + cytoskeletonToxoplasma
ER
Mt
DG
PM
IMCPM
IMCThe Inner Membrane Complex (IMC) underlies the parasite plasma membrane
6IMC: flattened vesicles + cytoskeletonToxoplasma
ER
Mt
DG
PM
IMCPM
IMCThe Inner Membrane Complex (IMC) underlies the parasite plasma membrane
6IMC: flattened vesicles + cytoskeleton
Gliding machinery: - MyoA - MLC1 - GAP45 - GAP50 - GAP40
Toxoplasma
ER
Mt
DG
PM
IMCPM
IMCThe Inner Membrane Complex (IMC) underlies the parasite plasma membrane
6IMC: flattened vesicles + cytoskeleton
Cytoskeletal elements: - Microtubules - Alveolins - GAPMs - ISPs
Gliding machinery: - MyoA - MLC1 - GAP45 - GAP50 - GAP40
Toxoplasma
Spatial-temporal organization of the IMC is critical for Plasmodium differentiation
7
MD Lazarus et al, J Cell Sci 121:1937-‐49; 2008 LG Tilney, unpublishedMD Lazarus et al, J Cell Sci 121:1937-‐49; 2008
Parasitophorous vacuole (PV) Parasite Plasma Membrane Inner Membrane Complex (IMC)
Merozoite Trophozoite Schizont
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of apicomplexa
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of apicomplexa
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of apicomplexa
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of apicomplexa
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
defining features of apicomplexa
> 5000 species of parasites
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Interpreting parasite life-cycles
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?• Can there be more than one host species?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?• Can there be more than one host species?• How are the host species geographically distributed?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?• Can there be more than one host species?• How are the host species geographically distributed?• How does transmission occur?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?• Can there be more than one host species?• How are the host species geographically distributed?• How does transmission occur?• What cell type(s) does the parasite infect?
Interpreting parasite life-cycles
• What is the definitive host (sexual reproduction)?• What is the intermediate host (asexual reproduction)?• Can there be more than one host species?• How are the host species geographically distributed?• How does transmission occur?• What cell type(s) does the parasite infect?• What are the major developmental stages?
gut gut
Red blood
cells
Sporozoites
into host
Sexual stages
in vector
Intestinal epithelium
Salivary glands
Intestinal
epithelium
Merozoites
Toxoplasma
Crypto- sporidium
Plasmodium
Theileria
Tick
M
osqu
ito
Cat
(Muscle,
neurons)
Mammalia
n
Host
Hep
atoc
ytes
Lym
phoc
ytes
Any
cel
l
(Bradyzoites)
Roos, Science 309:72-74 (2005)
Apicomplexa share similar life-cycle strategies
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Intermediate host!(asexual reproduction)
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
initial infection leads rapid cell invasion and parasite replication
from Gary Ward!Univ. of Vermont
Intermediate host!(asexual reproduction)
Dinkorma Ouologuem
14
Dinkorma Ouologuem
14
Dinkorma Ouologuem
14
Dinkorma Ouologuem
14
15
15
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Toxoplasma life-cycle
Hunter & Sibley. Nature Rev. Micro. 2012
Asexual reproduction occurs in intermediate hosts
Toxoplasma life-cycle
Toxoplasma life-cycle
Toxoplasma life-cycleSexual reproduction occurs in Felidae (definitive host)
Toxoplasma life-cycleSexual reproduction occurs in Felidae (definitive host)
18
18Kreuder, et al., J. Wildlife Diseases, 2003
18Conrad, et al., IJP, 2005Kreuder, et al., J. Wildlife Diseases, 2003
18Conrad, et al., IJP, 2005Kreuder, et al., J. Wildlife Diseases, 2003
18Conrad, et al., IJP, 2005Kreuder, et al., J. Wildlife Diseases, 2003
Torey & Yolken, TrePar, 2013
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Cryptosporidium: sexual and asexual reproduction occur in the same tissue of the same host
very resilient!common contaminant of water
ID50 = 100-300 cysts
Cryptosporidium = ‘hidden spore’
NEJM, March 1995
Cryptosporidium = ‘hidden spore’
NEJM, March 1995
Cryptosporidium = ‘hidden spore’
~400,000 people affected!69 people died (93% had HIV/AIDS)
• GEMS set out to identify infectious causes of mild to severe cases of pediatric diarrhea in developing countries !• 7 study sites in Africa and SE Asia; 3 year study!• ~10,000 children with MSD and ~13,000 controls (0-5yrs)!• multiplex diagnostics leveraging a variety of molecular and standard microbiological assays.
The Lancet, July 2013
The Lancet, July 2013
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Plasmodium life-cycle
Plasmodium life-cycle
Plasmodium life-cycle
Malaria
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
220 million people infected in 2010
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
220 million people infected in 2010
most are in sub-Saharan Africa
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
220 million people infected in 2010
most are in sub-Saharan Africa
over 600,000 deaths in 2010 alone
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
220 million people infected in 2010
most are in sub-Saharan Africa
over 600,000 deaths in 2010 alone
90% of these are in children under age 5
MalariaRanks as one of the ‘big three’ in
total mortality for infectious diseases
220 million people infected in 2010
most are in sub-Saharan Africa
over 600,000 deaths in 2010 alone
90% of these are in children under age 5
global prevalence has dropped 25% since 2000
Why is malaria so deadly?
Miller, et al., Science, 1994 vol. 264: 1878-1883.
Why is malaria so deadly?
Why is malaria so deadly?
Why is malaria so deadly?
Why is malaria so deadly?
P. vivax
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
Phylogeny of protozoan parasites
kinetoplastids
Leishmaniasis
cutaneous
Leishmaniasis
cutaneous mucocutaneous
Leishmaniasis
cutaneous mucocutaneous visceral
Leishmaniasis
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
kinetoplastids
African Trypanosomes"T. bruci rhodesiense (East African Sleeping Sickness) - only 2% of disease, acutely progressive!T. bruci gambiense (West African Sleeping Sickness) - accounts for 98% of disease
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
kinetoplastids
African Trypanosomes"T. bruci rhodesiense (East African Sleeping Sickness) - only 2% of disease, acutely progressive!T. bruci gambiense (West African Sleeping Sickness) - accounts for 98% of disease
tsetse fly
humans!buffaloes!
cattle
T. brucei (African sleeping sickness)
tsetse fly
humans!buffaloes!
cattle
T. brucei (African sleeping sickness)
tsetse fly
humans!buffaloes!
cattle
T. brucei (African sleeping sickness)
tsetse fly
humans!buffaloes!
cattle
T. brucei (African sleeping sickness)
Only 1% of tsetse flies are infected
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
kinetoplastids
American Trypanosomiasis"T. cruzi (Chagas disease)
Protozoa
alveolates
Fecal-oral
Foodborne
Mode of transmission
Coccidians
Cryptosporidium
Excavates
LeishmaniaTrypanosoma
ApicomplexaCiliates DinoflagellatesHeterolobosia Euglenoza Fornicata
major subgroup
Phylum
Genus
Naegleria Giardia
Insect vector
ToxoplasmaPlasmodium
'brain-eatingamoeba'
'traveler's diarrhea'
'traveler's diarrhea'
malariaChagas diseaseAfrican sleeping sickness
Kala azar
kinetoplastids
American Trypanosomiasis"T. cruzi (Chagas disease)
T. cruzi is transmitted by reduviid bugs
T. cruzi life-cycle
T. cruzi life-cycle