The Apicoplast: What it is and Why it’s Important

By Andra Sakson

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 apicoplast^2,3.

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

 

Thine State of Submission

By Talbrett Caramillo
 

Figure 1 Adult female Doryctobracon areolatus (Spepligeti), a parasitoid wasp of Anastrepha spp. Photograph by Charles Stuhl, USDA-ARS-CMAVE Gainesville, Florida.

Imagine that you are an insect currently in the larval stage of your development, living freely on the forest canopy, awaiting the next phase of your lifecycle which would be to cocoon yourself and metamorphize into that next stage where you might sprout wings and take to the skies. Suddenly, you are confronted by an enigmatic figure possessing a neurotoxin capable of rendering you a zombie, harboring dark complex eyes that peer deep into your soul with sinister goals in mind: to find that suitable host species, paralyze them, and lay the progeny within that target host so that the future of that species may continue their way of life. Such organisms exist in this world we inhabit, they are known as the parasitoid wasps.

Background 
  In the world of parasites, there are many forms of organisms that are specifically adapted to their hosts. Such parasitic specifications are none more impressive than that of the world of wasps belonging to the order Hymenoptera, and their parasitoid lifestyle, and are often referred to as ecological specialists. Though some may recognize this order as being a primarily eusocial, most wasp species are known to be solitary creatures. One good quality of wasps is that they do not target people specifically, but if you happen to find yourself falling into their target host species range you might want to tread lightly. Wasps have a specific species that they must target, and some have even evolved neurotoxins in order to “zombify” their hosts. They don’t lay their eggs in external environment locations, but instead they lay their eggs within their targeted hosts that have been immobilized by the highly specialized venom as previously mentioned. Finally, wasp’s contribution to insect diversity is none more appreciated than by the ever so important field of agriculture. These wasps target pest species that would otherwise decimate valuable crops, costing farmers millions of annual revenues. Though farmers consider insecticides for pest control, I would argue that methods of utilizing natural pest control such as the wasps, as an adequate replacement for insecticides. Pest control is reasoning enough helping highlight these specialized organisms and continue to live their unique example of parasitism.

Diversity of Wasps  
The vast diversity of wasps is apparent in their different body sizes, but also their target host species. Some species are so small they would not be readily noticed without an untrained eye, while others can be about as big as one’s thumb. One such example of target host diversity, is that some wasps will target caterpillars, spiders and roaches just to name a couple of examples. Most wasps are very much small individuals, such as Chalcid wasps and contains over 20,000 different species of wasps. One can also imagine that different species of wasps will also have different techniques in which they subdue their hosts. The wasp’s size is one of their most distinct features, in that they are usually much smaller in comparison to their target host species. Being smaller, means they must have adaptations that make them much quicker than the host, and most can strike in their targets in an instance.

 
Host Manipulation
The search for suitable hosts is a highly specialized process but finding that unfortunate victim is merely the beginning of this mind-altering experience. In one of the most well studied examples, the Jewel Wasp targets cockroaches and controls the unlucky individual into following it into a burrow of its choosing. This host manipulation mechanism is made possible through their venom which is comprised of a variety of neurotoxins that target a certain region of the roaches’ Central Nervous System (CNS). Much of these mechanisms are present in other species of wasps and their preferred target host species. In the case of the Jewel Wasp, once it finds a target roach, it then attacks and uses a system of chemical cues within the roach’ CNS to correctly distribute the venom, making the roach manageable.  

Benefits of Parasitoid wasps 
Much of the benefits associated with the parasitoid wasps can be found in their ability to control pest species, that may otherwise become overpopulated and decimate the agricultural markets. Some might even go as far as to use wasps as bio-controls of these pest species, but there could be problems associated with the introduction of a species to a new ecological system. Though they are efficient controllers of pests, the wasps are highly susceptible to pesticides that might be ever present in most agricultural operations. In closing, parasitoid wasps are a unique example to the world of parasites. Their lifestyle seems taken straight out of a horror movie, and their unfortunate hosts that exhibit the zombie state. Thought they are fun to learn about and study, you do not want to find yourself as the target host species of these efficient killers.

References

E. Zchori-Fein et al. “A newly discovered bacterium associated with parthenogenesis and a change in host selection behavior in parasitoid wasps.” Proceedings of the National Academy of Sciences Oct 2001, 98 (22) 12555-12560; DOI: 10.1073/pnas.221467498

Gal, Ram et al. “Sensory Arsenal on the Stinger of the Parasitoid Jewel Wasp and Its Possible Role in Identifying Cockroach Brains.” PLoS ONE 9.2 (2014): n. pag. Web.

Zhu, Feng et al. “Symbiotic Polydnavirus and Venom Reveal Parasitoid to Its Hyperparasitoids.” Proceedings of the National Academy of Sciences 115.20 (2018): 5205–5210. Web. 9 Mar. 2020.

  https://projects.ncsu.edu/cals/course/ent425/library/compendium/hymenoptera.html