Lecture 6: Parasite Survival Strategies Flashcards
What are the clinical stages of African sleeping sickness and what is the critical difference in treatment of these two stages?
In the first stage the parasite is only in the blood and has characteristic systemic symptoms: fever, headache, malaise, etc. In the second stage the parasite has crossed the blood-brain-barrier and causes a reversion in the sleep/wake cycle (hence the name sleeping sickness), neurological symptoms like mental disturbance. Finally they go into a coma and die. The critical difference in treatment is that for the second stage of Eastern African sleeping sickness, there is no effective treatment.
How is African sleeping sickness called in cattle?
Nagana
What controls the differentiation and proliferation of the Trypanosoma?
Cyclin-dependent kinases control the differentiation and proliferation of the Trypanosoma
What is striking about the lifecycle of Trypanosoma?
There is alternating proliferation and differentiation
What is striking about the energy production in Trypanosoma?
They only have one mitochondrion per cell. This is strange because all other eukaryotes (except for a family of protozoa) have more than one mitochondria per cell. This also means that in cell division of Trypanosoma, a new mitochondrion needs to be created. They have a lot of DNA in that mitochondrion interlinked like a “maliënkolder”.
What is different about the mitochondrial DNA of Trypanosoma?
There is a lot more and it is organised in mini and maxi circles that are highly interconnected. This makes it more difficult to separate and makes replication take longer.
Why does the mitochondrial genome not reflect the proteins in Trypanosoma?
It is highly edited at RNA level. mRNA is edited with different mechanisms. Within the mitochondrial RNA are also guide-RNAs (small RNAs) that bind to mRNA and bases are either inserted, deleted or chimeras are formed.
Why is it useful to edit mitochondrial mRNA in Trypanosoma?
Because they have only one mitochondrion, and it is sensitive to mutation.
What are glycosomes?
They are basically peroxisomes. They have the same import system and are comparable in part of the content (etherlipid biosynthesis, isoprenoid biosynthesis, β-oxidation of >C20 fatty acids). The differences are that glycosomes do not have catalase, have a pyrophosphate metabolism and have compartmentalised glycolysis and nucleotide biosynthesis.
What is striking in clinical measures during Trypanosoma infection?
The amounts of parasites in the blood fluctuate heavily
What causes the fluctuation of the amount of Trypanosoma in the blood?
The Trypanosomes have Variant Surface Glycoprotein or VSG on their outer surface. The adaptive immune system will form antibodies against this VSG. Once these antibodies have been formed, the immune system will use the membrane attack complex on these parasites, activate complement. The population of Trypanosomes decreases. However, Trypanosomes have antigenic variation. One parasite will express another VSG and escape the immune response. This cycle then repeats itself, causing the fluctuation of the amount of Trypanosoma in the blood. It is important to remember that this antigenic variation does not occur because of the immune pressure! It will happen in lab culture as well.
Where are the DNA for VSGs located?
On telomeres of the chromosomes.
How are the VSGs connected to the Trypanosoma membrane?
They are GPI-anchored
How is the expression of VSG genes switched?
There are three different mechanisms that occur with different frequencies: in situ switch, telomere exchange and gene conversion. In situ switch: the genes remain in the same place, one is just activated instead of the other. Telomere exchange: One gene has an expression site, this gene is switched out for a different gene that did not have an expression site. This “crossing over” happens during replication. Gene conversion: There are multiple genes without an expression site, one of these replaces a gene with an expression site.
How is Ascaris lumbricoides successful with a complex lifecycle like it has?
The eggs are sticky, so they stick to eggs. They infect their hosts for a long time so they can produce a lot of eggs, meaning they increase the chances that one of their offspring will infect a new host. It also helps that they don’t cause a lot of disease, because they keep their host alive long enough to produce sufficient offspring.
What are the implications of the high distance of helminths in the phylogenetic tree?
The worms are not a single phylogenetic cluster and treatment of these different worms requires distinct therapeutic drugs.
