Model Organisms: The Unholy Trinity: Crithidia fasciculata as a model for Kinetoplastid research by Cameron Jack Stockwell
This article was written by Scientist Cameron Jack Stockwell, PhD Candidate, Leeds Beckett University
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| Image 1 of T. brucei. (Credit: DPDx, CDC) |
African
Trypanosomiasis (sleeping sickness) is a disease caused by parasites. It is characterised
by rash, enlarged lymph nodes, malaise and neurological problems caused by invasion
of the central nervous system. Infections are caused by Trypanosoma brucei
rhodesiense, which can kill within months, and T. b. gambiense which
often kills within 3 years of infection. Currently there exists no cure for the
diseases.
The
parasites are transmitted through the bite of the Tsetse fly when it takes blood meal and are difficult to treat due to
their ability to hide within the skin but remain undetected in blood serum
samples.
Another
parasite related to T. brucei is Leishmania which causes
Leishmaniasis. Visceral
leishmaniasis has up to 90,000 new cases a year and is fatal when untreated.
Disease is characterised by fever, rapid weight loss, and swelling of the liver
and spleen. One form of the disease causes lifelong scars and destruction of
nasal, mouth and throat membranes. Although Leishmania is treatable,
more effective treatments are still required.
Due to the
infective and deadly nature of these organisms, non-human infective model
organisms are often employed in research. Often, a parasite of mosquitos, Crithidia
fasciculata that is closely related to both Leishmania and T.
brucei is used to investigate the effects of novel drugs, DNA repair and
the roles of proteins within the organism. Like T. brucei and Leishmania,
Crithidia is a Kinetoplastid organism, named so due to the presence of a
kinetoplast, the bundle of DNA, that sits within the mitochondrion.
Crithidia is much easier and cheaper to culture than Trypanosoma and Leishmania. The low cost is highly advantageous to smaller research groups and those testing a large range of new drugs. As it does not infect humans it is safer too, requiring Biosafety Level 1 or 2 compared to the more specialised level 3 labs used for parasitic Trypanosome research. The increased accessibility is great for research institutes that cannot facilitate specialist labs or expensive specialised equipment that is required for research. The close biochemical and genetic relationships of the parasites mentioned make Crithidia an ideal model for investigation into mitochondrial DNA and repair mechanisms used within the Kinetoplastid parasites.
Crithidia is much easier and cheaper to culture than Trypanosoma and Leishmania. The low cost is highly advantageous to smaller research groups and those testing a large range of new drugs. As it does not infect humans it is safer too, requiring Biosafety Level 1 or 2 compared to the more specialised level 3 labs used for parasitic Trypanosome research. The increased accessibility is great for research institutes that cannot facilitate specialist labs or expensive specialised equipment that is required for research. The close biochemical and genetic relationships of the parasites mentioned make Crithidia an ideal model for investigation into mitochondrial DNA and repair mechanisms used within the Kinetoplastid parasites.
Although Crithidia
is non-human infective and lacks many features that allow Trypanosoma
and Leishmania to strive within humans, many other biochemical pathways
are present. The low costs associated with the organism make it ideal for
preliminary research and gives a faster throughput due to short generation
times associated with it.
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Image 2:
Fluorescent images of C. fasciculata. (Credit: Cameron Jack Stockwell)
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| Cameron J. Stockwell |
Several
systems have already been developed to use C. fasciculata as a model
organism. DNA vectors such as pNUS, have been produced to allow effective
fluorescence analysis of proteins present within the organism. As the full
genome is also sequenced, the study of Kinetoplastid genes is quicker in Crithidia
than in its parasitic cousins as well. The use of Crithidia as a model
organism is growing, and more advanced techniques are being continually
developed.
Cameron is a
PhD candidate in virology at Leeds Beckett University who has previously worked
with Crithidia fasiculata. He can be found @ScienceManCam on twitter.
Sources & further reading:
interesting, thanks for the article. I didnt even know of the existence of Crithidia, until one day when examining a squashed mosquito under a dark-filed microscope I saw what I at first though was a Leishmania. But eventually on comparison of what I saw with images found on the web, concluded it was a perhaps a Crithidia, This kindled an interest, and I found this article which suggest that compartively rare and as of yet unknown pathogenic significance, yet they can infect humans ... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974865/
ReplyDeleteAnd I wonder whether if amongst other things, this might explain the intense itching reaction I experience in response to some mosquito bites and not others?
Here is another reference to similar organism in case of human infection https://stacks.cdc.gov/view/cdc/84844/cdc_84844_DS1.pdf
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