Eliminating Nuclear Pollution Using Algae - Coccomyxa actinabiotis

When you imagine a pool of water filled with high concentrations of toxic metal debris and uranium from a nuclear power plant, what do you think of?  Do you think lethal, deadly or completely inhospitable?  If so, you would be, for the most part, correct.  Such conditions are fatal to nearly every living cell on the planet.  However, a recently-isolated algae found in a nuclear material storage site named Coccomyxa actinabiotis is able to not only survive in such conditions, but can even thrive.  Such an organism can prove a useful tool in slowing the increasing levels of nuclear waste due to the development of nuclear power.

In our current situation of constantly increasing demand for energy, nuclear power presents a valuable source of electricity: nuclear reactors currently supply the world with 13% of its total electricity, and nuclear energy processes produce virtually no greenhouse gases.  With carbon emissions becoming an increasing threat to global temperatures by the year, nuclear power is likely to become a popular alternative to more air-polluting energy production tactics such as coal-burning plants.  However, with this revolution in energy will come a different pollutant in the form of particles known as radionuclides.  Radionuclides are high-energy, unstable atoms that are an inevitable product of nuclear fission that takes place in energy-producing nuclear plants¹.

Many nuclear power plants utilize a water-based system in which water is run by a reactor to harness the heat energy of the nuclear reactions.  In this way, radionuclides leak into the water, which must be removed before the water is reused¹.  The methods by which this is done (such as precipitation, evaporation, ion-exchange, etc.) are energy-intensive and expensive².  Additionally, any leaks of radioactive material, such as the explosion of the Fukushima power plant in 2011, are dealt with via blunt and inefficient methods, such as manual washing and concrete isolation of contaminated surfaces³.  Therefore, a radionuclide-cleaning technique such as bioremediation presents an appealing alternative to current detoxification processes.

Modern nuclear spill cleaning techniques involve

time-intensive and ineffective manual washing.

Bioremediation is the use of microorganisms to render hazardous materials harmless.  Such a strategy is cost-effective, allows decontamination of large areas such as bodies of water, and is generally gentle on the environment.  This technique is already used in the nuclear industry using organisms such as genetically-modified yeasts, though these microbes require a significant amount of nutrients and are not as efficient at concentrating radionuclides as certain cells that are naturally resistant to radioactivity.  Examples of these promising specimens with high natural radiation resistance are mostly cells without nuclei, such as Pyrococcus furiosus or Deinococcus radiodurans.  However, the nucleated algae Coccomyxa actinabiotis presents one of the most convenient specimens for bioremediation deployment for a multitude of factors: it has demonstrated extreme resistance to both radionuclides and heavy metals, it has natural mechanisms to turn radionuclides into inert substances, and it is photosynthetic².

Electron microscopy of C. actinabiotis

cells. Note the bright green coloration

indicative of the photosynthetic

chloroplasts in the algae.

First, what makes environments filled with radionuclides so hostile?  In high levels of radiation, very small particles such as gamma or beta rays are emitted from decaying radionuclides.  These rays are able to penetrate cells and nuclei where they can fragment and mutate the cell's DNA.  Excessive levels of genetic destruction are fatal for the cell.  Amazingly, C. actinabiotis is capable of surviving and reproducing in radioactivity of up to 20,000 Gy - a concentration of radionuclides that can shatter glass and plastics².  As a more relatable point of comparison, a full-body dose of radiation that is internally measured at only 5 Gy is lethal to 50% of humans after one month of the initial exposure⁴. 

The methods by which C. actinabiotis and other cells survive this harsh environment are varied, but all depend on maintaining the integrity of the organism's DNA.  It is known that C. actinabiotis actively accumulates deadly radionuclides and uses them in certain biochemical pathways, partially detoxifying them and concentrating them within the cell membrane.  Currently, however, there is little thorough research on the specific mechanisms by which this resistant algae lives in such intense radiation.  Studies on the non-nucleated, radiation-resistant organism D. radiodurans indicate that microbes can use techniques such as enhanced gene repair mechanisms and maintaining multiple genome copies to combat radioactive gene damage.  Additionally, supplementary experiments have suggested that C. actinabiotis is capable of restoring its entire genome in the event of severe radioactive mutation, allowing continued growth and multiplication².

In addition to radionuclides, C. actinabiotis can also withstand extremely high concentrations of toxic metals such as cobalt and silver.  Using a high-resolution imaging technique, it was found that cobalt ions become highly concentrated outside of C. actinabiotis chloroplasts, suggesting that cobalt is possibly used within the chloroplasts to produce nutrients.  The imaging also revealed that silver ions are spread evenly throughout the inside of the cell.  Silver may or may not be used in C. actinabiotis biochemical reactions, but it is, at the very least, highly isolated from compartments in which it can interfere.  Alternatively, silver ions may be bound to other molecules that render it harmless to vital biochemical pathways⁵.

These properties, when uniquely combined in a single organism, make for a relatively superior tool for cleaning hazardous environments.  While species such as D. radiodurans are capable of surviving in high concentrations of radionuclides, they are heterotrophic microbes.  This means that they require other microorganisms to feed upon, which is difficult for these cells to accomplish in bioremediation environments when nuclear material kills most, if not all, D. radiodurans prey species⁶.  C. actinabiotis, on the other hand, is a photosynthetic algae.  Thus, all it requires to clean toxic substances is light and a carbon source, making it far more applicable in situations in which bioremediation is necessary.  Additionally, most microbes that are resistant to either radioactivity or heavy metals are not resistant to the other: D. radiodurans, while highly radionuclide-resistant, cannot tolerate high toxic metal concentrations.  C. actinabiotis is capable of handling high concentrations of both types of substances simultaneously, giving the organism unparalleled versatility in the detoxification of dangerous materials⁷.  Lastly, most currently used bioremediation species require intensive genetic manipulation in order to possess traits such as detoxification and resistance⁶.  C. actinabiotis is capable of performing these actions naturally, requiring less lengthy and expensive manipulations of DNA².

So, finally, how would C. actinabiotis actually be used as a bioremediation tool?  Upon being placed on a contaminated surface or in a contaminated body of water, C. actinabiotis will begin absorbing radionuclides and heavy metals at a rapid pace, concentrating and purifying them to a certain extent.  Eventually, most of the contaminants will be contained within cell bodies, which can then be gathered and disposed of by incineration or other such disposal methods.  Alternatively, trapped heavy metals can be recycled from these algae cells to be reused in various industries².

In conclusion, the process of using C. actinabiotis as a nuclear decontamination tool can occur without genetic manipulation and with only a source of light energy and carbon atoms.  Thus, the end result of such a treatment is an area cleansed of both dangerous radionuclides and toxic metals with relatively little energy investment and minimal environmental harm².  No other microorganisms currently known, nucleated or not, can equal the versatility, resilience and simplicity by which this novel algae absorbs and concentrates deadly atoms.  Acquiring such an efficient technique of resolving radionuclide pollution can allow nuclear power to completely meet world energy demands without suffering the consequences of radioactive contamination.

References:

1. Zinkle, S.J. (2013). Materials challenges in nuclear energy. Acta Materialia. 61(3). Pgs. 735-758. Retrieved from http://www.sciencedirect.com/science/article/pii/S1359645412007987

2. Rivasseau, Corinne, et. al. (2012). An extremely radioresistant green eukaryote for radionuclide bio-decontamination in the nuclear industry. Energy and Environmental Science. 6. Pgs. 1230-1239. Retrieved from https://hal-agrocampus-ouest.archives-ouvertes.fr/hal-00796855/document

3. Brumfiel, Jeff. (2011). Fukushima set for epic clean-up. Nature. 472. Pgs. 146-147. Retrieved from http://www.nature.com/news/2011/110411/full/472146a.html

4. Caso, C. et. al. (1999). Section 5.4 Radioactivity and Radiation Protection. Review of Particle Physics. Retrieved from http://xdb.lbl.gov/Section5/Sec_5-4.pdf

5. Leonardo, T. et. al. (2014). Determination of elemental distribution in green micro-algae using synchrotron radiation nano X-ray fluorescence (SR-nXRF) and electron microscopy techniques – subcellular localization and quantitative imaging of silver and cobalt uptake by Coccomyxa actinabiotis. Metallomics. 6. Pgs. 316-329. Retrieved from http://pubs.rsc.org.ezp1.lib.umn.edu/en/content/articlepdf/2014/mt/c3mt00281k

6. Misra, Chitra Seetharam et. al. (2012). Recombinant D. radiodurans cells for bioremediation of heavy metals from acidic/neutral aqueous wastes. Bioengineered. 3(1). Pgs. 2165-5979. Retrieved from http://www.tandfonline.com/doi/full/10.4161/bbug.3.1.18878

7. Rivasseau, Corinne et. al. (2011). U.S. Patent No. 20130078707. Retrieved from http://www.google.com/patents/US20130078707

8. Associated Press. (Mar. 10, 2013). Japan struggles to clean up after tsunami, nuclear disaster. The Oregonian.  Retrieved from http://www.oregonlive.com/today/index.ssf/2013/03/japan_struggles_to_clean_up_af.html

Zooxanthellae and Coral- a Love Story

by AN

The ocean is home to many fascinating creatures that have created their own magical undersea world. An important role in this world is played by the dinoflagellate Zooxanthellae. Zooxanthellae are single cell marine organisms that rose to fame by their association with coral reefs. The two organisms have a mutually beneficial relationship that- like most relationships- can get complicated under stressful conditions. Coral provide zooxanthellae with carbon and a cozy, protected habitat with plenty of sunshine. In turn, the zooxanthellae will use the carbon to undergo photosynthesis. The coral will be awarded about 90% of the sugars, lipids, and oxygen produced by their tenants for growth and respiration. Furthermore, the coral can use the photosynthesis byproducts to strengthen and lengthen their calcium carbonate skeleton (1). This is an inspiring process of recycling that results in almost no wasted energy or nutrients. Unfortunately, this relationship is traveling down a bumpy path and coral reefs are suffering greatly. Zooxanthellae are beginning to move out of their coral homes due to conditions caused by global climate change. This results in the process of coral bleaching, where corals lose their defining color and structure and have trouble engulfing enough nutrients.

Coral reefs are home to a wide range of marine

diversity, including this beautiful parrot fish. 

Zooxanthellae can exist as free-living cells or in symbiosis with marine creatures. In the free-living state, they have two flagella that they lose during colonization of a host. They are sensitive to any stressors in the environment, and prefer to reside in temperatures colder than 33 degrees Celsius. Even a slight increase in temperature can have dire consequences. Global warming is a huge concern for these microscopic eukaryotes, as the ocean temperature has already risen 0.85 degrees Celsius in the last century (2). When zooxanthellae undergo changes in temperatures, they are no longer able to provide sufficient nutrients for their coral, and are expelled from their homes. The coral then lose their color slowly starve to death (2). Another preferred condition of zooxanthellae is clear ocean waters, to soak in maximum light energy from the sun. In turbid waters, they have more trouble photosynthesizing (3). If they cannot produce enough food for themselves or their coral, they will die, leaving their coral bleached and devoid of nutrients. Bleached coral are also more susceptible to disease, which suggests that zooxanthellae are able to outcompete other microorganisms for colonization (1). When the zooxanthellae no longer colonize coral, they risk invasion of deadly disease and illness. Pollution of the oceans and global climate change are enemies of zooxanthellae; when their environment becomes turbid and warmer, the coral symbionts will seek a new home.

An important genus of zooxanthellae is Symbiodinium, which form obligate mutualisms with stony corals. The Symbiodinium genus is the most well studied zooxanthellae, and a common symbiont of coral. Symbiodinium displays extensive genetic diversity. They are spherical shaped cells and contain a multilobed chloroplast. Their genome contains twenty-six chromosomes, guarded inside of a relatively large nucleus (4). Due to the diversity observed within this genus, it is classified into different groups, or clades, based on genetic similarities. Within the eight different clades of this genus, there are multiple subclades, or strains. Different strains contain different DNA and display different phenotypic behaviors. A coral rarely inherits its zooxanthellae, and must acquire them in open waters. However, occasionally the Symbiodinium will be inherited vertically and transmitted from parent to offspring. The environmental conditions in the location of the host encourage specific pairings between mutualistic partners (5). One coral can host multiple strains of Symbiodinium, and even display selective behavior in their affiliation with certain strains. Some strains are able to combat higher temperatures, and therefore seasonal shuffling of Symbiodinium strain is not uncommon for a stony coral (6). By adapting this behavior of selectively hosting heat tolerant symbiotic zooxanthellae, coral reefs may find a way to thwart global warming (7). In fact, it has been shown coral reefs that are most severely affected by climate change have adopted Symbiodinium that are resistant to warmer temperatures (7). If ocean temperatures continue to increase, however, zooxanthellae may not evolve fast enough to save its hosts and even the most heat tolerant strains will have trouble surviving. Environmental impacts imposed by humans have already devastated 30% of the world’s coral, indicating the Symbiodinium may not survive the drastic changes (1).

From here.

However, there is a beacon of hope for tropical coral reefs: Symbiodinium clade D. It will persevere higher temperatures and provide coral with stress resistance, possibly saving future generations (1). Genetic biomarkers are used to distinguish clade D from the other eight clades, but categorizing species and subclades has been a persisting dilemma. Clade D Symbiodinium are considered generalists, and occupy a wide variety of hosts. Its low host specificity could either be attributed to properties that allow the dinoflagellates to survive diverse environments, or that it is less likely to be evicted by its host because of thermal resistance.  However, corals that adopt Symbiodinium clade D in times of stress will allow their original strains of zooxanthellae to repopulate within 3 years (1). Further investigation of this phenomenon should involve close monitoring of coral symbionts before, during and after exposure to an increase in water temperature. It is possible that more common clades, such as B or C, can out compete clade D in certain environments. Coral that harbor clade D grow more slowly than those who are colonized by clade B or C, so once the coral no longer perceives thermal stress as a threat, they could prioritize faster growth over stress protection (1). The fitness trade-offs of clade B or C versus clade D explain coral shuffling of the Symbiodinium. There has been disparity of heart resistance within clade C, suggesting that the clades continue to evolve and adapt to climate change or that horizontal transfer occurs between clades.

Coral reefs give life to an incredible amount of marine biodiversity. The ecosystem they provide can be almost entirely attributed to the dinoflagellate mutualists residing inside of them. If global warming succeeds in killing marine zooxanthellae, it will endanger an abundance of marine life that relies on coral reefs for protection and housing. With rising temperatures of the ocean comes coral bleaching, which is highly correlated with coral reef mortality. It is the responsibility of microbiologists and marine biologists of the world to commit to saving these beautiful eukaryotic microbes that give the ocean so much life. Further investigation of the genetic diversity and stress adaption of Symbiodinium species will pave the way to providing coral reefs with the necessary nutrient to rebuild its community.

References:

1.     Stat, M and Gates, R. Clade D Symbiodinium in scleractinian corals: A “nugget of hop, a selfish opportunist, an ominous sign or all of the above. Journal of Marine Biology. 2011.

2.     University Corporation for Atmospheric Research. How much has the global temperature risen in the last 100 years. https://www2.ucar.edu/climate/faq/how-much-has-global-temperature-risen-last-100-years

3.     Douglas, A.E. Coral bleaching-how and why. Marine Pollution Bulletin. 46(4); 385-392. April 2003.

4.     Noaa ocean service education. March 2008. http://oceanservice.noaa.gov/education/kits/corals/media/supp_coral02bc.html

5.     Blnk, R.J. Cell architecture of the dinoflagellate Symbiodinium sp. Inhabiting the Hawaiian stony coral Montipora verrucosa. Marine Biology. 94(1); 143-155. February 1987.

6.     Coffroth, M and Santos, S. Genetic diversity of symbiotic dinoflagellates in the genus Symbiodinium. Protist. 156(1); 19-34. June 2005.

7.     Mieog, J et al. Quantification of algal endosymbiont (Symbiodinium) in coral tissue using real-time PCR. Molecular Ecology Resources. 9(1).January 2009.

8.     Baker, A et al. Coral reefs: Coral’s adaptive response to climate change. Nature. 430(741). August 2004.

Overly Attached Parasite

by KP

Trichomonas vaginalis is an extremely common human parasite that primarily infects vaginal cells as well as other cells of the urinary tract and the cervix, particularly in older women. It is estimated that T. vaginalis infects between 5 and 8 million in the United States and over 100 million worldwide each year. This makes trichomoniasis the most transmitted non-viral STD in the world. These staggering numbers are likely because T. vaginalis is easily transmitted and can be transmitted through non-penetrative sex and the sharing of clothing. Trichomoniasis is very treatable, with the normal treatment being a single dose of antiprotozoan drugs (1). Despite the fact that T. vaginalis often is present without symptoms, it is still a very important human pathogen because it has been shown to increase the risk of HIV infection, cervical cancer, and preterm delivery in pregnancy (2).

As a parasite that grows on the outside of host cells, the adhesion of T. vaginalis to host cells is key for it to cause symptoms and increase risk (3). The pathogen primarily causes damage to cells of the epithelium, the cells that line the outside of hollow structures and glands in the body. This adhesion to host cells is hugely important to T. vaginalis infection as it is actually unable to kill or damage host cells without adhering to them.

Transmission of trichomoniasis only occurs when it’s in trophozoite form. The trophozoite form is how the parasite lives for most of its life cycle. When it adheres to vaginal cells, the structure of the parasite changes from its trophozoite form to its flatter amoeboid form and has more contact area with host cells (Figure 1). The amoeboid form has increased adhesion between the parasite and host cells because of the increased area over which the parasite and host cell interact. After adhesion, T. vaginalis lyses, or in other words kills, infected cells. The parasite is then able to migrate across the epithelium causing the characteristic inflammation associated with trichomoniasis (5). People will experience inflammation of the vagina and the urethra.

Figure 1: Scanning electron microscopic images of T. vaginalis. A is the trophozoite form in a broth culture. B is the trophozoite form adhering to a vaginal epithelial cell before transformation to its amoeboid form. C is the amoeboid form adhering to a vaginal epithelial cell. (4)    

This essential cell to cell attachment can be mediated by many different types of proteins, lipids, or sugars. The adhesion molecules are a part of a broader category of molecules called virulence factors. These are important to understanding T. vaginalis infection because they are responsible for the parasite’s ability to infect and cause symptoms. Host cells also have surface molecules, which are referred to as receptors, and will attach to molecules on the surface of parasites. These molecules do not intentionally allow attachment by T. vaginalis and other parasites. Generally the host cell surface molecules play important roles in the healthy lifecycle of the cell. Parasites like T. vaginalis have evolved to exploit the fact that the molecules are necessary.

There are also many environmental conditions on which successful infection of vaginal epithelial cells by T. vaginalis depends. Temperature, pH, zinc levels, iron levels, and host immune response are all environmental factors to which make T. vaginalis infection more or less likely (6). These environmental factors can also make symptoms more severe. The adhesion step alone is impacted by several of these environmental characteristics such as iron levels and host immune response.

Lipophosphoglycan (LPG) is one adhesion molecule that regulates the surrounding environment to make infection worse. It has been shown that when LPG contacts host cell this causes the host cell to produce more signals that recruit immune cells to the site of infection. While immune cells are important for protecting our bodies from infection, the immune cells themselves can cause inflammation and damage to tissues in an effort to get rid of infections by any means necessary. The immune signals also exacerbate the infection by recruiting additional T. vaginalis cells to the site of infection (7).

LPG is a molecule made up of a lipid part and a sugar part found on the surface of T. vaginalis cells. As stated earlier, LPG is important to the adhesion of parasites to host cells. LPG in T. vaginalis has parts made of a type of sugar called galactose that are bound by the host cell surface protein Galectin-1. This host cell receptor not only plays a significant role in vaginal infections, as it can be found on just about any type of cell (8). This is one of the main reasons trichomoniasis can occur in the urethra in addition to the vagina.

Like LPG, proteins called cysteine proteases help to mediate adhesion of the parasite to host cells while causing damage to infected cells (9). Unlike LPG, cysteine proteases on the parasites do not manipulate the host immune system to cause inflammation. Cysteine proteases on the surface of T. vaginalis cells were found to damage anti-microbial and anti-inflammatory proteins found on the surface of vaginal epithelial cells (10). The cleavage of the anti-microbial and anti-inflammatory proteins by cysteine proteases is thought to be the main cause of the increased risk of developing HIV in individuals infected with trichomoniasis. Secretory leukocyte protease inhibitors (SLPI), which are specifically targeted by cysteine proteases, were shown to inhibit HIV infection of mucous membranes.

Cleaving proteins like SLPI is not the only strategy cysteine proteases use to cause symptoms. The cysteine protease CP30 was also shown to turn on a pathway that leads to apoptosis, or programmed cell death, in host cells (11). The process of CP30 causing apoptosis appeared to be somewhat dependent on the amount of available iron during infection. In high iron environments, CP30 activity was lower overall and in lower iron environments, CP30 levels were increased (12). This finding and the existence of other virulence factors regulated by iron implicates the menstrual cycle as some sort of factor that allows trichomoniasis to persist if untreated (13, 14). It should be stated that an exact relationship between menstruation and the persistence of untreated Trichomonas infection is not currently known.

                  Without adhesion, T. vaginalis would not be able to parasitize other cells or cause any of the characteristic symptoms of trichomoniasis. Attachment is not only important to the health of host cells, it also causes important changes in the structure of the parasite. LPG on the parasite attaches to Galectin-1 on host cell. This causes the host cell to release immune signals. These immune signals worsen the infection by recruiting immune cells and additional parasitic cells to the site of infection. T. vaginalis also causes inflammation using the protein CP30, which destroys anti-microbial and anti-inflammatory proteins found on the surface of host cells. Iron levels regulate CP30 levels, which suggests a possible relationship between trichomoniasis and the menstrual cycle. The ways that T. vaginalis adheres is also a big part of the reason why trichomoniasis increases the risk of HIV and cervical cancer and why this organism can impact human health so greatly despite being a relatively minor illness.

References

1)     Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. Morbidity and Mortality Report. 64(3), 72 – 75 (2015).

2)     Schwebke JR, Burgess D. Trichomoniasis. Clinical Microbiology Reviews. 17(4), 794 – 803 (2004).

3)     Alderete JF, Lehker MW, Arroyo R. The mechanisms and molecules involved in cytoadherence and pathogenesis of Trichomonas vaginalis. Parisitology Today. 11(2), 70 – 74 (1995).

4)     Arroyo R, Gonzalez-Robles A, Martinez-Palomo A, Alderete JF. Signalling of Trichomonas vaginalis for amoeboid transformation and adhesion synthesis follows cytoadherence. Molecular Microbiology. 7, 299 – 309 (1993).

5)     De Miguel N, Riestra A, Johnson PJ. Reversible association of tetraspanin with Trichomonas vaginalis flagella upon adherence to host cells. Cellular Microbiology. 14(12), 1797 – 1807 (2012).

6)     Figueroa-Angulo EE, Rendon-Gandarilla FJ, Puente-Rivera J, Calla-Choque JS, Cardenas-Guerra RE, Ortega-Lopez J, Quintas-Granados LI, Alvarez-Sanchez ME, Arroyo R. The effects of environmental factors on the virulence of Trichomonas vaginalis. Microbes and Infection. 14, 1411 – 1427 (2012).

7)     Fichorova RN, Trifonova RT, Gilbert RO, Costello CE, Hayes GR, Lucas JJ, Singh BN. Trichomonas vaginalis lipophosphoglycan triggers a selective upregulation of cytokines by human female reproductive tract epithelial cells. Infection and Immunity. 74(10), 5773 – 5779 (2006).

8)     Okumura CYM, Baum LG, Johnson PJ. Galectin-1 on cervical epithelial cells is a receptor for the sexually transmitted human parasite Trichomonas vaginalis. Cellular Microbiology. 10(10), 2078 – 2090 (2008).

9)     Arroyo R, Alderete JF. Trichomonas vaginalis surface proteinase activity is necessary for parasite adherence to epithelial. Infection and Immunity. 57(10), 2991 – 2997 (1989).

10)  Draper D, Donohoe W, Mortimer L, Heine RP. Cysteine proteases of Trichomonas vaginalis degrade secretory leukocyte protease inhibitor. Journal of Infectious Disease. 178(3), 815 – 819 (1998).

11)  Sommer U, Costello CE, Hayes GR, Beach DH, Gilbert RO, Lucas JJ, Singh BN. Identification of Trichomonas vaginalis cysteine proteases that induce apoptosis in human vaginal epithelial cells. Journal of Biological Chemistry. 280(25), 23853 – 23860 (2005).

12)  Kummer S, Hayes GR, Gilbert RO, Beach DH, Lucas JJ, Singh BN. Induction of human host cell apoptosis by Trichomonas vaginalis cysteine proteases is modulated by parasite exposure to iron. Microbial Pathogenesis. 44, 197 – 203 (2008).

13)  Garcia AF, Chang TH, Benchimol M, Klumpp DJ, Lehker MW, Alderete JF. Iron and contact with host cells induce expression of adhesins on surface of Trichomonas vaginalis. Molecular Microbiology. 47(5), 1207 – 1224 (2003).

14)  Hsu HM, Lee Y, Hsu PH, Liu HW, Chu CH, Chou YW, Chen YR, Chen SH, Tai JH. Signal transduction triggered by iron to induce the nuclear importation of a Myb3 transcription factor in the parasitic protozoan Trichomonas vaginalis. Journal of Biological Chemistry. 289(42), 29334 – 29349 (2014).

Hide and Seek: Evasion of Immune Response by Trypanosoma cruzi

By Ben Lueck

            For as long as life has existed on this planet, every organism has been entangled in a fierce competition for survival.  This competition is introduced by the finite amount of nutrients required to support life in any given environment, meaning that whichever organism can obtain and utilize the greatest amount of nutrients can continue living, and ultimately reproduce.  This competition is ruthless, essentially a fight to the death where nothing is off limits.  Common tactics for survival include sequestering all of the resources to starve your competition, directly preying on weaker competition, or even poisoning your competition.  In the face of such brutal battle tactics, a very simple solution is often employed by organisms that cannot compete head on; find a place in which you can live, and hide.  There are no limits to where organisms can hide, and some of the most successful “hiders” are parasites that have found ways to live inside of other organisms.  In response to parasites and other pathogens, higher organisms have evolved ways to fight off these invaders.  Specifically, humans have evolved a complex immune system that is highly capable of coordinating responses to effectively kill invaders.  However, there are still holes in the human immune system, and one parasite in particular, Trypanosoma cruzi, has found ways to exploit these holes.

Romana's sign, a manifestation of
acute Chagas disease.

            Trypanosoma cruzi is a single celled human parasite best known for causing Chagas disease in South America, and the CDC estimates that 8 million people are currently living with Chagas disease.¹ T. cruzi is transmitted to humans from the Triatominae insects, commonly called “kissing bugs.”  These insects are so named because they tend to bite humans on the face, especially around the mouth and eyes.  When these insects bite a human and ingest a blood meal, they engorge to the point that they defecate on the host.  The feces containing the infectious T. cruzi cells can then enter the bite wound passively, but is more often actively smeared into the bite wound by the human host when they itch the bite.  Once inside the host, T. cruzi can enter the bloodstream and cause Chagas disease. 

            Chagas disease is defined by having two major stages of infection; an acute phase and a chronic phase.  The acute phase occurs immediately after T. cruzi infection, and while capable of manifesting as severe disease, is almost always mild, including only non-specific signs and symptoms including swelling, fever, and body aches.²  After the acute phase, the infection moves to the chronic stage, which is a prolonged and persistent infection.  Chronic infection is asymptomatic in 60-80% of individuals³, however 20-40% of chronic infections eventually lead to severe damage of the heart, nervous system, and digestive system.⁴ As previously mentioned, humans have an immune system to kill parasites and other pathogens.  How then, does T. cruzi consistently evade being killed by the immune system to cause a persistent infection?

            Before answering this question we must first explore the human immune system. The human immune system is extremely complex, composed of many branches, each of which contains a multitude of components.  The two major branches of the immune system are the innate immune system and the adaptive immune system.  The innate immune system’s primary job is to create barriers to keep foreign organisms outside of our bodies, and provide an extremely fast response when these barriers to infection break down.  To provide this timely response, the innate immune system is less specific than the adaptive immune system. 

Two branches of the immune system.

            The adaptive immune system on the other hand, is extremely specific for foreign cells, and more effective at killing them.  The adaptive immune system is divided into two main branches, one of which is composed of the B cells in our bodies that produce antibodies in response to pathogens.  The other branch is composed of T cells, of which there are two major types.  The T cells are divided by function into “killer” T cells, cells that are highly efficient at killing their target cell, and “helper” T cells, that function to coordinate the immune response between B cells, T cells, and the innate immune system.  The adaptive immune system is also capable of creating memory for pathogens.  However, this specificity and memory comes at a cost, being that this response takes 3-5 days to prime.⁵ As you can probably appreciate by now, the immune system has many components, and it takes a lot of communication to coordinate action between all of these components.  To do this cells use signaling molecules, called cytokines, to communicate with each other and coordinate action by all of the specialized cells.

            For a pathogen to most effectively break down the immune system, it must interfere with multiple components of the immune system.  This is indeed the strategy employed by T. cruzi, and this allows the infection to exist persistently and evade effective immune response indefinitely.  The first evasion tactic employed by T. cruzi is that it uses a wide range of acquired factors to enter many different types of cells in the human body.  This allows the parasite to hide from the immune system, which sees the host cell as normal, and cannot detect the parasite inside the cell.  Another evasion tactic used by T. cruzi is to interfere with the process of phagocytosis. Phagocytosis is carried out by specialized cells of the innate immune system called phagocytes, and is the process by which cells take up foreign material in a specialized compartment called a phagosome.  The phagosome is then fused with another specialized compartment called a lysosome, which is full of specialized products used to degrade the contents of the now mature phagolysosome.  This process is usually effective at killing foreign cells, but T. cruzi can escape from the compartmentalized phagolysosome, avoiding death, and continue living inside of the cell.⁶ The infected cells attempt to call for help using cytokines when they become infected, but T. cruzi blocks the production of these cytokines, and therefore other cells do not receive the message that the phagocyte is infected.⁶ 

            T. cruzi not only avoids components of the innate immune system, but the adaptive immune system as well.  T. cruzi is capable of altering the process by which T cells are made and activated, preventing the immune system from creating sufficient numbers of killer and helper T cells.⁸ This inhibits killer T cells from killing infected host cells to release the pathogen for killing by other cells, and allows T. cruzi to remain hiding in tissues as a persistent infection.  The absence of helper T cells also inhibits the coordination of immune response.  In addition, T. cruzi alters the process by which antibodies are produced, preventing the immune system from producing a quality antibody response.  This combination of evasion tactics, among others not mentioned, combine to create an environment that allows for T. cruzi to persist in tissues and consistenly evade immune response, making the parasite a formidable opponent for the human immune system.

            After discussing the numerous battle tactics of Trypanosoma cruzi mentioned here, one might ask: “why hasn’t Chagas disease wiped humans off the face of the planet?”  Well, T. cruzi is a hider, not a killer. As a parasite it is more beneficial to live in your host than to kill the host and lose your home. When it comes to facing the human immune system, it seems that Trypanosoma cruzi is more interested in playing hide and seek than going to war.

References

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