1.1 Kinetoplastid parasites Flashcards
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1.1 ** <!--[endif]-->Kinetoplastid parasites**
LO
Learning Objectives
By the end of this lecture, you should be able to understand:
- How kinetoplastids are classified and some of the reasons behind this classification
- Some key features relating of kinetoplastid cell biology/biochemistry
**Mark Wiser – Protozoa and Human Disease (on PDF) **
**We will be focusing over the next four weeks on a series of infections that are collectively known as the kinetoplastids **
What is the classificaion overall schema?
Domain: Eukaryota
Phylum: Eugenozoa
Class: Kinetoplastida
Order: Trypanosomatida
Genus: *Phytomonas, Leptomonas Blastocrithidia*,
- Crithidia, Trypanosoma*, LeishmamiaSpecies: T. brucei, T. cruzi, T. evansi, T. equiperdum,
- T. congolense , T. vivax*, T. suis, L. major,
* L. donovani, L. infantum, L. brazilenesis**, etc
Those in bold are the medically relevant that we will be focusing on *
What classification domain are they?
Prokaryotes / Eukaryotes?
Classification Domain: eukaryotes
They are eukaryotes (true nucleus) – NOT VIRUS – NOT BACTARIA
They have a nucleus, they have membrane-bound organelles, mitochondria
They are not that simple, this single cell has the metabolic capacity to live, it poses the entire metabolic capability
Classification Phylum: Eugenozoa (flagellate)
What is one of the closest relatives of kinetoplastids?
Where does the flagellar enter the cell body?
What processes are carred out at *^
Is it only flagella - what else?
What else has been argued with regards to the role of the flagella?
One of the closest relatives of the Kinetoplastids are the euglenoids which are predominantly photosynthetic free living organisms. Fresh water living Euglena are very closely related to the parasitic kinetoplastids
The flagellar itself enters the cell body by the flagellar pocket structure which is the mouth and anus of the parasite, this is where the parasite carries out the process of endocytosis i.e taking things from outside e.g taking up nutrients, and also the site of exocytosis (trying to get rid of things)
Everyone thinks that flagellar is only for motility, but how useful is this? Parasite will not be able to swim against the flow of a humans blood stream. In certain cases, it might be useful but what appears to be the case for the use of the flagellar is a whole raft of other things. For example attachment. It can use the flagella in the right conditions, it can use the flagella to attach to epithelial layers and remain within one part of the insect vector.
Also argued that there has been signal transduction molecules along the flagellar, it can actually play a role in sensing the new environment (not known yet but possible find out over the next five years)
The Euglenozoa (phylum) is split into two major classes
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- <!--[endif]-->Euglenids
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- <!--[endif]-->Kinetoplastids
Where do the kinetopasdis get there name? Where is this structure found?
Where is this structure located?
The kinetoplastida (kinetoplastids) get there name because of the structure found within there mitochondria called kinetoplast which is basically the mitochondrial genome (see diagram above, it is located close to the flagellar) it gives the class name of these organisms.
The order: Trypanosomatida
What does this mean?
Are all members of this order parasitic?
Where do these parasites prefer to be (host)?
What can the human be thought of?
Trypanosomatida basically just means (cork screw motion)
All members of this order trypanosomatida are parasitic all are primarily pathogens of insects although there are a number that can have a secondary host.
A lot of the parasites that we will discuss prefer to be in insects are there hosts. We are just there to help the parasite get from host to host. From this view humans act as vectors for the parasite to move from insect to insect
Classification Genus:
The different genera (genus) that make up the trypanosomatida (as we have said are all parasitic) include
- Leptomonas
- Blastocrithidia
- Crithidia
What are all of these? Where do they live?
These are all pathogens or parasites of various insects and live within the digest tracts within the insect vector and spread through insects, through feces.
They infect only insects and primarily live in the digestive tract
Another genus of the trypanosomatida is the genus **phytomonas **
Where are these prodominately found?
How are they tansmitted?
Again these are predominately found in the digestive tracts of insects but they also infect plants.
Transmitted to plants by the feeding habbits of the vector, e.g from the saliva of the insect to the plant.
From the plant perspective you can find phytomonas all over the plants
How are they transmitted?
Are they a problem from an agricultural perspective?
They are transmitted via the feeding habbits of the insect vectors - in the saliva from the insects
They are not that much of a problem from an agricultural point of view because they don’t impinge on us as humans.
Classification Genus: Trypanosoma & Leishmania
The anmals that do impinge on mammals an other animals and there activities are better studied are the genera trypanosoma and leshmania
Where are they primarily found?
Where can they be transmitted - what organisms?
How are they transmitted?
The genera trypanasoma and leishmania again the vast majority are parasites of insects, as a group they can be transmitted to a raft of animals: fish, amphibians, birds and other mammals. If you go out into the wild most organisms are infected by a trypanosomia or leishmania species.
They are transmitted from the insect vector by its feeding habits, different species use saliva, so basically the parasite is spat out so trypanosoma brucei – we talk about this afternoon it is a salivarian parasite.
Passed from insect vector to human in the salaiva
T. brucie tranmistted by kissing bug/assasin - they bite to the face (kissing) as they epand they shit and you rub it in
Classification Genus: Trypanosoma & Leishmania
Are they medically important
These are the medically important parasites that Dr. W will be taking about
T. brucei causes HAT
T. cruzi causes Chagas disease - endemic in latin america
Leishmaniasis caused by multiple speciesof leishmania- whic cause a raft of pathologies
Trypanosoma & Leishmania
Do they just infect humans?
What else can they infect?
Where is t. brucei found?
What do trypanosom’s cause?
Don’t just infect humans
They can infect any mammalian organism, e.g T brucei is mainly found in ungulates (hoofed mammals) particularly cattle thus a major problem from an agricultural perspective. In cattle and other ungulats, they cause a serious weight losing disease
Nagana in cattle
Surra in equine
These are wasting diesese that are all insect transmitted
Most are insect transmitted - one species is no insect transmitted and that is the parasite of horse T . equiperdum a close relative of T brucei
Most trypanosoma are insect transmitted apart from?
what is it a close relative of?
What is dourine?
How is it transmitted?
Is there alot of pharmaceutical interest?
Are there any agricultural affects?
T. equiperdum which is a close relative of t. brucei
Trypanosomia species that is not insect transmitted is a parasite of of horses called trypanosoma equiperdum, this is closely related to the HAT and t. brucei.
They are very closely related t. equiperdum causes a venereal disease in horses called Dourine or covering skiness. The parasite has evolved an alternative mechanism of transmission to that of insect as a vector. That alternative transmission has resulted in this disease being in horses.
// Worry – could there be a possibility of t. brucie become an STI? \
Lack of pharmaceutical interest or investment – neglected in terms of drug development
Veterinary implications are huge; nagana in cattle and surra in equines caused a loss of income of about $5 billion in agriculture – this is because people people eat cattle but also used to plough fields.
Trypanosoma & Leishmania: basic morphology
** Complex life cycles = different morphologies**
Cell shapes…
**Where are they found in humans? **
Where can t. cruzi infect?
Where is leishmania specilised too? is it intracellular parasite what is it limited to?
Why do you need to have difference parasite forms?
Where within the host wil they live?
In humans they are found in different parts of the human cell, t. brucei is found in fluids so it is an extracellular parasite i.e found in the blood stream, found in the lymphatic system, also found in cerebral spinal fluid –
Whereas in humans t. cruzi can invade any nucleated cell within your body It can invade cells – intracellular pathogen
Leishmania is specialised intracellular parasite, it can only invade neutrophils and macrophages
Thus, there needs to be different parasite forms to live within those different environments, likewise parasite live in different places within the insect. T bruci lives in the midgut of the insect vector and then also in the salivary gland of the insect vector - leishmania stays in midgut and lives there before it is vomited up t. cruzi undergoes transmission through the gut and will have different morphological forms throughout the midgut
Trypanosoma & Leishmania: basic morphology
Different morphologies (also called parasite forms) distinguished by:
- Position of kinetoplast relative to nucleus
- Posiion of flagella pocket relative to nucleus
- Presence/size of flagellum
4 Presence of undulating membrane where as other parasites dont have the undulating membrane structur linking flagella to cell body
Different parasite forms – can be recognized by the position of the kinetoplast relative to the nucleus, the position of the flagellar pocket relative to the nucleus. Usually the kinetoplast and the flagellar are usually tightly linked so they go together – also the presents and size of the flagellar. There are certain parasite forms specifically the intracellular forms of t. cruzi where they have a very stubby flagellar whereas with the life cycle stages of t. bruci presents a flagellar throughout and then the flagellar is sometimes linked back to the cell body by a structure called the undulated membrane – other parasites don’t have this. More details in lectures
Start looking at the microbiology and biochemistry
Trypanosoma & Leishmania: key features
Mitochondrion
How many do they have per cell?
What stucture does it have?
What do you use to stain for this?
Only has one of per cell,
< EM reading through a cell (picture), if you stripe away everything apart from the mitochondria you get a strange looking skeleton, the mitochondria spreads through the whole of the cell it has a complex lattice structure spread throughout cell you can stain for this using a dye (mitotracker – labels mitochondria)
Mitochondrion - readily visualised using selective dyes (eg Mitotracker)/ confocal microscopy
What is the red blob?
One mitochondria is there throughout the cell
There are two genomes within trypanosome’s – it stains in this case it stains the nucleas, red faint haze then you get the red blob, the kinetoplasts sit in the middle between these two discs
Kinetoplast
The kinetoplast acts as a marker for cell cycle (along with flagellum)
What does the kinetoplast act as within the cell cycle?
What can you compare?
If it is in the G1 phase? How many nuclues how many kinetoplasts?
Are there multiple types of kDNA? What form are they in?
You can use the kinetoplast to compare the ratio of kinetoplast to the nucleus to get an idea of where it is within the cycle.
1N1K you are in the G1 phase, 1N2K you are in the G2 phase, 2N2K you are in the M phase you can use this to look at cell populations are a whole and see where they are within the cell cycle.
There are multiple types of kDNA within the kinetoplast itself it is composed of 2 classes of circular DNA
They form highly concatenated structure they are intertwined - individual circular DNA molecules interconnected to form complex network, looped together like the Olympic rings and as a result o this they form a mesh network of interconnected complex
