12 Flashcards
Leishmania
Infection causes human disease
Transmitted by sand flies (non dividing form)
Proliferate in humans & other animals
Not well understood disease
Sub-pellicular microtubules form a network underneath the plasma membrane that encompasses the entire cell.
Secretory Pathway
Roughly similar to mammalian cells. Contain ER, Golgi, trans- Golgi, secretory vesicles, etc. However, all secretory vesicles appear to be routed to the Flagellar Pocket (fp), an invagination of the plasma membrane at the anterior end of the cell
Leishmania Promastigotes Express Multiple
Abundant Surface Macromolecules
Abundant cell surface glycolipid lipophosphoglycan (LPG) - a major component of the cell surface ‘glycocalyx’.
However, there are other abundant surface molecules that contribute to this surface coat. These include:
PPG, proteophosphoglycan, a highly glycosylated poly-peptide
gp63, the major surface glycoprotein which has protease activity
GIPLs, glycosylinositol phospholipids.
Structure of Lipophosphoglycan (LPG)
Lyso-Alkyl-Phosphatidylinositol - tethers the glycolipid into the
membrane via the single saturated fatty acid side chain on the
glycerol moiety.
Heptasacharide Core - 7 sugars
Repeating phospho-disaccharide - ~16 repeats
Cap - galactose/mannose branched structure
LPG functions in Leishmania
Attachment to insect midgut
Resistance to complement when promastigote is injected into tissue
Attachment to macrophage receptors for invasion
Resistance of parasites to oxidative attack inside macrophage
Modulation of macrophage signaling cascades
Leishmania genome
Poly-cistronic coding sequences
Abundant RNA binding proteins
Extensive membrane surface glycoconjugates
Leishmania has Small Numbers of Very Long Polycistronic Transcripts
few promoters
2. Genes must be regulated post-
transcriptionally, since many different
genes are transcribed from a single promoter
to generate a poly-cistronic transcript.
. Individual mRNAs must be generated
by processing the polycistronic transcript.
This is done by trans-splicing of a spliced
leader sequence onto the 5’ end of each mRNA
and by polyadenylation of the 3’ end.
Trypanosoma brucei
Transmitted by blood sucking insects and are found in the circulatory system of the bitten host.
Trypanosoma brucei (gambiense or rhodescience) –
Cause African sleeping sickness
Transmitted by the tsetse fly.
Trypanosoma brucei
The mitotic division of is unusual in terms of the cytoskeletal process.
The basal body plays a key role in the organisation of the spindle.
Stages of mitosis:
Replication of basal body associated to kinetoplast
Kinetoplast undergoes replication
Second flagellum grows while nuclei replicates
Mitochondria divides and cytokinesis continues from anterior to posterior end
Cells not always separate after mitosis
Trypanosoma brucei
Cellular structure typical of an Eukaryote
Single mitochondria with a mitochondrial DNA structure called kinetoplast
Kinetoplast is associated to a flagellum that provides mobility in the blood stream
The cell coat displays several glycoproteins
Four distinct cellular forms
Trypanosoma cruzi
Causes Chagas’ disease
Transmitted by the reduviid bug (“kissing bug”) which bites and defecates at the same time. The feces, containing the organism contaminates the bite wound and the organism gets in to cause the infection.
Cells in almost all of the internal organs can be invaded.
Cardiac problems and meningoencephalitis are the leading causes of death.
A major problem in Central and South America.
Trypanosoma genome
Half of the genome is non-coding (retro-elements)
Large number of surface proteins
Highly conserved transmembrane proteins
Unconventional mitochondrial genome
Plasmodium falciparum
Causes Malaria in humans Transmitted by Anopheles mosquito Most significant parasite in humans Complex life cycle Not treatment available
Plasmodium proteome
Large number of hypothetical proteins
1% of the proteome is targeted to organelles
A quarter have transmembrane domains
High similarities to the proteome of Arabidopsis thaliana (a model plant species)
Organelle genes transfered to nuclear genome
