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Summary lectures Molecular Parasitology
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English summary of all the lectures given during the course Molecular Parasitology.
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1 The parasite within1.1 A parasitic way of life
Parasitism – the most successful life style
- The majority of organisms have adopted a parasitic way of life
- Plenty of food available while usually keeping the host alive (for as long as required)
- Host organisms provides a stable and often protective environment
- Bacteria, viruses, prions, ‘selfish DNA’
Definitions
- Host = An organism that is infected with or is fed upon by a parasitic or pathogenic organism.
- Definitive host = a biological organism in whose body a parasite sexually multiplies and
completes its life cycle.
- Vector = A carrier of a disease-causing agent from an infected individual to a non-infected
individual or its food or environment
- In sexual reproduction, an organism combines the genetic information from each of its
parents and is genetically unique. In asexual reproduction, one parent copies itself to form a
genetically identical offspring.
Parasites mutilate and manipulate
- Cymothoa exigua is the only parasite known to functionally replace an entire organ
- Leucocholoridium paradoxum infection land snails attract their definitive host, birds, by
aggressive mimicry moving the snail’s eye stalk resembling of a caterpillar
- horsehair worms cause their cricket and grasshopper hosts to jump in water
- Ophiocordyceps species turn the ants they infect to zombies, which climb the trees and lock
their jaws in leaves at the ideal growing conditions for the fungus
We are all populated by parasites; everyone is infected by a parasite at some point of their lives.
Malaria – poverty comes at a price
Plasmodium falciparum is a protozoan parasite
responsible for causing malaria in humans. The
life cycle of Plasmodium falciparum involves
several stages and alternates between the
human host and the female Anopheles
mosquito:
1) Transmission to humans: during blood
meal, the mosquito injects sporozoites
(infective form of parasite) into the
human bloodstream
2) Liver stage (exoerythrocytic stage):
sporozoites travel to the liver, where
they invade hepatocytes > sporozoite
develops into thousands of merozoites
3) Release of merozoites: hepatocytes
rupture > release of merozoites into bloodstream
1
, 4) Blood stage (erythrocytic stage): RBC infected > inside RBCs merozoites undergo a series of
developmental stage (incl. ring state, trophozoite stage, schizont stage)
5) Asexual replication: production of multiple daughter merozoites > infected RBC rupture >
infection of new RBC (clinical symptoms occur)
6) Gametocyte formation: some merozoites differentiate into sexual forms called male and
female gametocytes. When a mosquito bites and infects person, it ingests these gametocytes
along with the blood
7) Mosquito stage: inside the mosquitos stomach, the gametocytes undergo sexual
reproduction to form zygote > develop into ookinetes > traverse to the mosquito midgut wall
and form oocysts on the outer surface
8) Spore formation: oocysts undergo sporogony > sporozoites
9) Transmission to humans: mature oocysts burst, releasing sporozoites into the mosquitos
salivary glands, once it reaches the bloodstream, the cycle is restarted.
Focus on unicellular protozoan parasites
Protozoa are unicellular eukaryotes. As in all eukaryotes, the nucleus is enclosed in a membrane. In
protozoa other than ciliates, the nucleus is vesicular, with scattered chromatin giving a diffuse
appearance to the nucleus, all nuclei in the individual organism appear alike.
- Toxoplasma, the most common protozoan
parasites in human, is an apicomplexan parasite
and distant relative to the free-living ciliate
described the godfather of microbiology, Antonie
van Leeuwenhoek
Prokaryotes are always unicellular, while eukaryotes are
often multi-celled organisms. Additionally, eukaryotic cells
are more than 100 to 10,000 times larger than prokaryotic
cells and are much more complex. The DNA in eukaryotes is
stored within the nucleus, while DNA is stored in the
cytoplasm of prokaryotes.
Not one current life form is ancient/primitive: all stood the test of (evolutionary) time.
1.2 The parasite challenge
You are a single-cell parasite, and you have found a fantastic spot with plenty of food, however, this
is a hostile environment with a variety of immune cells in search and destroy modus. How do you
stay safe?
- Evasion of detection: camouflage & changing of surface proteins
- Intracellular survival: invasion of host cells & modification of host cell machinery
- Antigenic variation: change surface antigens
- Immunomodulation: suppression of immune responses & avoidance of immune recognition
- Biofilm formation: create a protective layer that shield the parasite for direct contact with
immune cells
- Quorum sensing: communication systems
- Adaption to host environment: metabolic adaptation & temperature tolerance
- Rapid reproduction: high reproductive rate
2
,You are a single-cell parasite, and you are separated from the outside world by numerous
membranes, including your own and those of the vacuole and the cell you live in. You are safe now,
but how do you get your food?
- Exploiting hosts resources: nutrient uptake & energy production
- Manipulating host cell processes: inducing changes in host cell metabolism & reprogramming
host cell functions
- Symbiotic interactions: establishing mutualistic relationship to benefit both the parasite and
the host
- Mimicking host cell structures: camouflage
- Securing a niche: avoiding competition
You are a single-cell parasite, and you live inside a beautiful cell and really like it there, you have all
the food and safety you wished for, but still you need to grow and replicate. What do you do?
- Synchronized replication: minimize disruption and maximize the chances of successful
reproduction
- Cell division: employ host cells machinery for cell division and generate offspring within the
host cell
- Optimal resource utilization: accessing nutrients, energy, raw material from host
- Avoiding host cells damage: to prolong your stay and prevent host cell lysis
- Modulating host cell metabolism: directing resources toward processes that benefit your
growth and replication.
- Quorum sensing
- Evading host defences
- Maintaining homeostasis: adapting to changes in the host cell’s environment
- Establishing a niche for resources
- Long-term survival strategies: Develop mechanisms to ensure your long-term survival within
the host cell, perhaps even establishing a persistent infection that lasts for an extended
period.
You are a single-cell parasite, and you live in the blood of an animal, but it’s getting too crowded.
Where will you start looking for a new home?
- Tissue invasion
- Migration to other body fluids were resources might still be available (e.g. lymphatic fluid)
- Vector-mediated transmission
- Adaption to different host tissues
- Quiescent stage: Enter a quiescent or dormant stage, allowing you to survive in the crowded
environment until conditions become more favourable for seeking a new host.
- Trigger transmission mechanisms
- Environmental persistence: If the environment outside the host is suitable, explore
mechanisms for survival in the external environment, awaiting an opportunity to infect a
new host.
- Coinfection and competition: Investigate the potential for migrating to a different host
species, if compatible hosts are available. This could involve adapting to the immune system
and physiological conditions of a new host.
- Seasonal migration: If the crowded conditions are seasonal, explore the possibility of
migrating to a different part of the host or seeking new hosts during times when
environmental conditions are more favourable.
3
, You are a single-cell parasite, and you’ve made your way from the warm human blood to the cold
mosquito stomach. How do you cope?
- Temperature adaption
o Metabolic adjustment: Adjust your metabolic processes to function optimally at the
lower temperatures found in the mosquito stomach.
o Enter dormancy: Enter a dormant or quiescent state, slowing down metabolic
activities to conserve energy until a warmer environment is encountered.
- Avoiding digestive enzymes: Evolve mechanisms to resist or avoid digestion by the
mosquito's stomach enzymes. This might involve modifying surface proteins or producing
protective coatings.
- Camouflage: mimic mosquito proteins: Develop surface proteins that mimic those of the
mosquito stomach, reducing the likelihood of being recognized and attacked by the
mosquito's immune system.
- Vector exploitation: adapt to the new environment while preparing for the next stage of your
life cycle, such as forming transmission stages (e.g., sporozoites) that can survive in the
mosquito salivary glands
- Avoiding immune responses
- Utilizing available nutrients
- Attachment mechanisms: Develop mechanisms for attachment to the mosquito stomach
lining, providing stability and protection from the digestive environment.
- Timing of life cycle stages: synchronize with mosquito feeding cycle to optimize your chances
of successful transmission during subsequent blood meals
- Rapid replication
- Stress response mechanisms: Trigger stress response mechanisms that help the parasite
cope with the changing environmental conditions.
You are a single-cell parasite, and you can infect almost all mammals and birds, but can only sexually
reproduce in a cat’s gut. Currently you are stuck in a mouse. How are you going to solve this?
- Manipulation host behaviour: Induce changes in the behaviour of the infected mouse to
increase the likelihood of predation by a cat. Some parasites are known to alter host
behaviour to enhance their transmission.
- Attracting predators by chemical attraction
- Transmission through intermediate hosts
- Enhanced transmission through faeces: faecal shedding
- Altered reproductive strategy: if possible undergo asexual reproduction within the mouse
host to ensure a higher population density, increasing the chances that some parasites will
reach a cat host through predation
- Long-term survival strategies: encystment or dormancy
- Coinfection and competition: coinfect with other parasites or pathogens that are more likely
to infect cats
- Vector-mediated transmission
- Transmission through environmental factors
- Adapting to alterative hosts: expand host range
1.3 The web of life cycles
4
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