Background
You may have heard of the phylum of parasites called
Apicomplexa. It is almost exclusively comprised of parasites, including some of
the most deadly and widespread pathogens like Plasmodium which causes
the disease malaria. Other parasites include Toxoplasma gondii, the
causative agent of toxoplasmosis; Cryptosporidium spp, which causes cryptosporidiosis,
and Coccidia, an important parasite of wild and domestic animals2. These parasites are distinguished as
unicellular eukaryotes (single celled organisms, whose organelles are enclosed
by a membrane). Malaria is responsible for roughly
400,000 deaths and over a million cases of infection each year, making
treatments a highly prioritized area of research1. The unique feature of Apicomplexans, to which
their name is owed, is the apicoplast (see Figure 1). |
|
Figure 1. Apicomplexan parasite,
Plasmodium spp with major genomes and organelles illustrated. Note the
apicoplast!1
|
Apicoplast: What
is it?
The apicoplast is an organelle (think unicellular
version organ) that has a circular plastid genome (DNA arranged in a circle,
resembling that of a plastic). It is present in most apicomplexan parasites,
excluding Cryptosporidium spp. Plastids are the photosynthetic
organelles shared by most plants and algae, and apicoplasts are nearly
identical except that they lack photosynthetic genes2. Apicoplasts are surrounded by 4 membranes;
this is a major clue about their past! They provide essential functions for
apicomplexan parasites who would likely die without them.
Where did it come from?
The key to the development of the 4 membranes
around the apicoplast is a process called secondary endosymbiosis. Most corals
maintain symbiotic relationships with photosynthetic algae called
dinoflagellates. One algae that is closely associated with corals is Chromera velia, a greenish brown algae that possesses a red photosynthetic
algae symbiont3. Inside the red algae symbiont is a photosynthetic organelle called a
chloroplast, most likely derived from cyanobacteria (a photosynthetic bacteria)2. Initially, the cyanobacteria was engulfed by an ancestral alga and
became the chloroplast, surrounded by a membrane derived from the alga. Then,
the algal cell was engulfed by the Chromera velia algae, wrapping it
with another membrane derived from Chromera velia3. Because C. velia is closely related to apicomplexan parasites, it
is believed that evolution from this algae to parasite is what gave rise to the
apicomplexans3. The apicoplast then, is derived from the red algae symbiont of C.
velia. To review, the first membrane around the apicoplast is the
apicoplast’s own inner membrane (of cyanobacteria origin), the second membrane
is the apicoplasts own outer membrane, the third is from the red algae
that engulfed cyanobacteria, and the fourth is from the apicomplexan that
engulfed the algae. See blue labels in Figure 2 for illustration. |
|
Figure 2. Hypothesized development
of apicomplexan with apicoplast2,3.
|
Why do we care
about it?
The
apicoplast possesses genes that provide essential functions for apicomplexans
during development in the host. Let’s look at Plasmodium as an
example. Plasmodium spp goes through two primary stages in its host. The
first stage is the liver stage, where Plasmodium infects and develops in
the liver cells of a host. The second is the blood stage, where Plasmodium
reproduces in and ruptures the red blood cells2.
One
function of the apicoplast is isopentenyl pyrophosphate (IPP) synthesis, a
process that is essential for building proteins in the parasite. Experiments
have shown that IPP is only essential during the blood stage of Plasmodium3. Another function of the apicoplast is fatty
acid synthesis (FAS), a system for producing fatty acids that are building
blocks for lipids. Lipids are an important resource for building membranes in Plasmodium,
which enable it to grow. Studies have shown that Plasmodium only
needs FAS when it is in the liver stage. However, if the host is
malnourished there may be a shortage of lipids, causing plasmodium to
activate the FAS pathway in the blood stage as well4. Similarly, Toxoplasma activates FAS
to increase fatty acid production itself when there is a shortage of lipids in
the substance it is infecting4. In experiments where the FAS pathway was
removed from the apicoplast, and Plasmodium was placed in a
lipid-deprived environment, the parasite died. This is because it lacked the
resources to build membranes which is essential for growth4. When IPP is removed from the apicoplast,
the parasite also dies. However, experiments have shown that a Plasmodium parasite
lacking an apicoplast will survive if injected with IPP3.
All of these findings serve as important
research topics for developing treatments for apicomplexan parasites, and have
shown success in experimental models. The apicoplast is a complex component of
these parasites, and harbors a beautifully unique and complicated evolutionary
history. Because of its distinctive evolution into an essential organelle of
apicomplexan parasites, apicoplast alteration or removal seems detrimental to
the parasite. However, parasites are especially capable of adapting to new lifestyles
and optimizing their survival in the face of danger. Drugs targeting the
apicoplast should be taken advantage of, until of course the apicomplexans
adapt a new way of survival without their apicoplast sidekicks.
References
1. Khoury DS,
Zaloumis SG, Grigg MJ, Haque A, Davenport MP. Malaria Parasite Clearance: What
Are We Really Measuring? Trends Parasitol. 2020;36(5):413-426.
doi:10.1016/j.pt.2020.02.005
2. Loker
ES, Hofkin B V. Parasitology: A Conceptual Approach. New York, NY:
Garland Science; 2015.
3. McFadden
GI, Yeh E. The apicoplast: now you see it, now you don’t. Int J Parasitol.
2017;47(2-3):137-144. doi:10.1016/j.ijpara.2016.08.005
4. Amiar
S, Katris NJ, Berry L, et al. Division and Adaptation to Host Environment of
Apicomplexan Parasites Depend on Apicoplast Lipid Metabolic Plasticity and Host
Organelle Remodeling. Cell Rep. 2020;30(11):3778-3792.e9.
doi:10.1016/j.celrep.2020.02.072
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