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Parasite Biology > parasite organelles > Flashcards

parasite organelles Flashcards

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1
Q

protozoan classification

A
  • originally classified based on motility
    • flagellates, amoebae, ciliated protozoa, spore forming protozoa
    • not necessarily similar
  • genome sequencing more informative
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2
Q

parasitic protozoan organelles

A
  • often have unusual organelles
    • kinetoplasts
    • apicoplasts
    • amitochondrial
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3
Q

kinetoplastid protozoa

A
  • all have kinetoplasts
    • T. brucei
    • T. cruzi
    • Leishmania
  • all have a flagellar pocket
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4
Q

T. cruzi

A
  • american trypanosome
  • intracellular
  • similar appearance to african trypanosome
    • differs genetically
  • causes chagas diseas - american trypanosomiasis
    • endemic to south/central america
    • spread by triatomine bugs
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5
Q

T. brucei

A
  • african trypanosome
  • extracellular
  • causes african sleeping sickness (african trypanosomiasis)
  • endemic through tse tse fly belt of subsaharan africa
  • tse tse fly bites reservoir host and spreads infection through biting others
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6
Q

leishmania

A
  • intracellular
  • resides in macrophages
  • casues leishmaniasis
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7
Q

kinetoplasts

A
  • at base of flagellum
  • analogous to mitochondrion
  • contains kDNA
    • similar to mtDNA but present in circles
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8
Q

flagellar pocket

A
  • invagination where endocytosis takes place
  • vesicles bud off it and bring nutrients into the cell
  • shielded environment that is inaccessible to antibodies
    • location of invariant surface receptors that need to avoid immune detection
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9
Q

kinetoplast DNA

A
  • arranged in concatenated circles in disc-shaped kinetoplast
  • in each cell, one extended mitochondrion (kinetoplast) containing ktDNA
    • instead of 1000 mt per cell
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10
Q

kinetoplast genome

A
  • circular genome with concatenated disc of maxi-circles and mini-circles
  • ~100 copies of 20kb maxi-circles
  • thousands of copies of 1kb mini-circles
  • circles are interlinked
  • concatenated disc of mini-circles in one mini-circle thick and very compact
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11
Q

kDNA replication

A
  • complicated - requires replication of each individual circle fo the disc, which is spinning
  • disc surrounded by many replciation proteins
  • circles are detached, replicated and reattached to the disc by DNA topoisomerase II
  • nicks in replicated circles could act as replication markers
  • replication at same time as new flagella is made
  • in T. brucei, disc thought to osciallte between replicating factories
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12
Q

topoisomerase II

A
  • huge amounts needed
  • potential target for drugs and inhibition of kDNA replication
  • T. cruzi is sensitive to incubation with mitoxantrone
    • topo II inhibitor
  • also berenil
    • DNA binding drug
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13
Q

RNA editing in kinetoplast

A
  • compared to mitochondrial transcripts:
    • a lot of inserted U due to RNA editing
  • kDNA has defective mt genome
    • maxi-circles encode mt enzymes with defective transcripts
    • mini-circles encode small guide RNAs which act as correction templates for editing of dysfunctional transcripts
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14
Q

kDNA transcript repair

A
  • involves addition or deletion of U to non-functional precursor transcript
  • creates functional ORFs
  • gRNA has correct sequence
    • aligns defective transcript and repairs it
  • waste of energy but cell is parasitic so not an issue
    • possibly early mistake in mt amplified over time
    • not necessarily beneficial but not detrimental either
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15
Q

apicomplexan protozoa

A
  • plasmodium (intra)
  • toxoplasma gondii (intra)
  • contain apicoplasts
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16
Q

apicomplexan genome

A
  • nuclear DNA in chromosomes
  • mtDNA in 6kb circles
  • apicoplast DNA in 35kb circles
17
Q

apicoplast genome

A
  • thought to be analogous to mitochondrion
    • encodes ribosomal RNA, RNA and some protein coding genes
  • sequencing showed similarity to chloroplast - algal plastid
    • plastid - small replicating cytoplasmic organelle of plant/algal cells that contains pigments
  • very small genome compared to other plastids
  • transfer of metabolic pathway genes to nucleus
    • lateral gene transfer
  • endosymbiont reduced to fully dependent organelle
18
Q

apicoplast symbiosis

A
  • 2 successive symbiosis events leading to uptake of red alga producing nonphotosynthetic apicoplast
  • primary endoyctosis of free-living cyanobacterium by alga
    • organelle with 2 membranes - alga with a plastid
  • secondary endocytosis of alga by eukaryotic ancestor
    • loss of algal nucleus
  • yields organelle with 4 membranes
19
Q

role of apicoplast

A
  • disruption causes parasite death
  • may contribute to metabolism
  • plastid membrane contains solute transporters
    • allows host to benefit from plastid metabolites
  • plastid genome has subsequently been reduced after lateral gene transfer
20
Q

apicoplast metabolism

A
  • contains novel metabolic pathways
  • differ significantly from human host
  • biosynthesis of isoprenoids, fatty acids, heme
    • hijack of chloroplast synthesis pathway for heme synthesis
  • genome analysis reveals pathways
    • p. falciparum genome - 500 apicoplast proteins predicted, 150 have known homologs in metabolic pathways
21
Q

protein import into apicoplasts

A
  • bipartite protein signal required
  • similar to nuclear protein transport into chloroplasts
  • N-terminal signal sequence targets nuclear-encoded protein to ER
  • after translocation across outer membrane this is cleaved
  • exposes transit peptide region which targets the protein to the apicoplast
22
Q

apicoplasts as drug targets

A
  • blocking function causes cell death - good targets
  • antibiotics that target non-mevalonate (isoprenoid biosynthesis) pathway of bacteria should work against parasites like malaria
    • malarial enzyme homologs found
    • evidence for this pathway found in apicomplexa
    • fosmidomycin has had success
  • antibiotics target prokaryotes so shouldn’t affect host
  • knowledge of pathways and machinery is key for effective drug development

Parasite Biology (5 decks)

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