Saturday, December 8, 2012

Trichomonads Knockout Round

by HL

The enigmatic world in which we live seethes with danger. Silent killers lurk around every corner, assassins strike from the inside out and armies of natural born attackers wait to be released. This is the world of disease-causing microorganisms. Each organism competes to win the title of the fittest, most reproductively successful. Nothing will stop them in the race for survival. In this arena, the time has come for the final round among a group of parasitic flagellated protozoans, the Trichomonads. Nature has weeded out the weak, and only the top contenders remain, each displaying its most convincing and deadliest attributes. Trichomonas vaginalis, emerging from the depths of the urogenital tract in humans, will compete against T. gallinae, a seasoned fighter in the upper intestinal tract of its columbiform hosts.

While each organism occupies a distinct niche, they share crucial characteristics that aid them in the difficult life of parasitism, such as a similar build. In the class of flagellated protozoans, they possess not one but five flagella, four of which protruding from the cell and aiding in locomotion. Though they lack power-producing mitochondria, they harbor an interesting organelle, the hydrogenosome. This organelle not only has the capacity to produce essential energy for the cell, but it contains powerful antioxidant potential, without which this anaerobic microbe would succumb to the noxious effects of oxygen. These fighting machines are equipped with a barbed tail, or axostyle, ready to do serious damage to the host by latching onto tissues, causing irritation and inflammation1. Neither can live freely and therefore is vulnerable to the dangerous environment of its host, stashing clandestine mechanisms to elude the immune system of those it infects.
Image of T. vaginalis 

Let’s focus in on T. vaginalis. This contender is no small fry, weighing in with a hefty genome comparable in size to the human genome.2 Within its genome are 60,000 protein-encoding genes organized into six chromosomes, which enable it to adapt to diverse environments and be prepared for changes in pH, temperature, iron and zinc levels3. T. vaginalis is a strong predator, engulfing bacteria, vaginal epithelial cells and erythrocytes by phagocytosis. It is loaded with an array of attack mechanisms including toxic chemicals or cytotoxins that blow holes in erythrocyte membranes. T. vaginalis is a sneaky invader, penetrating the next victim in synchronization with the sexual activities of its human hosts, allowing it to invade the vaginal tract in women and the urogenital tract in men. The parasite breaks through a formidable wall of mucus to latch onto the epithelial cells of the vaginal lining6. Once attached, the invader morphs into an amoeba, increasing contact with the vaginal epithelial and creating its own minienvironment where it is capable of manipulating the pH and other factors till it can produce enough toxins to lyse the cell3.

The offensive strategies are average in comparison with its mechanisms of defense. These tactics are crucial when the host fights back. Nonetheless, T. vaginalis infects 250 million globally each year and Trichamoniasis is responsible for over half of the reported STI infections 5. Its success may be due to its unique mechanism to remain undetected by the powerful immune system of humans. T. vaginalis effectively resists lysis by thwarting the activity of complement proteins that guard the precious host, wait to attack a foreign invader and bring in more troops to help fight. In addition, it is armed with protein cleavers which degrade human immunoglobulin secreted by the host to rid the parasite7. It can also destroy a line of defense provided by the secretory leukocyte protease inhibitors residing in the mucus, rendering the inhibitors non-functional8.

Despite all this, there are more obstacles to overcome. The vagina of a female human host is an inhospitable place, highly acidic and constantly changing due to the raging hormonal influence producing a thick menstrual flow. The cells in the vagina are constantly sloughed off so T. vaginalis must maintain its iron grip on the host, lest it be wiped away by the current. Why does this microbe tolerate this bombardment from a menstrual female? Despite the unfavorable conditions, the vagina is an iron oasis compared to the zinc rich protstatic fluids encountered in the male which are toxic to the helpless protozoan. In the vagina, there is a reducing environment, which actually activates some pathogenic mechanisms of T. vaginalis.

Burrowing in the depth of the nucleus of T. vaginalis, a seething accomplice waits to ambush the unknowing host. This parasite itself is infected with up to four species of viruses, the Trichomonavirus, which exclusively infects the Trichomonas genus. Each virus wreaks its own havoc within the cell, changing the heterogeneity in the expression of certain cell surface proteins causing an aggregation of cell masses to form a syncytia, which then lyses and dies, releasing the virus4. Surprisingly the virus and protozoan live in harmony; the former provides the latter with phenotypic variation of surface immunogens on the molecule. Proteins such as P270 which are only expressed in T. vaginalis infected with the dsDNA virus are localized by the iron rich environment to the surface and confuse the host immune system9. Targeting T. vaginalis with antifungal medication alone is futile, as the virus is then released, triggering a cascade of host alarm signals that inflame the infected area. The response to the virus renders the patient more susceptible to devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer5.

With T. vaginalis battling for dominance against its human host, T. gallinae steps up in a different arena as a dangerous enemy to the avian community. This parasite infects mainly columbiform birds, such as the common carrier pigeon but occasionally can take down the most majestic birds of prey and delicate song birds. Its ability to jump avian host taxonomic groups can have dramatic effects in an instant. Disease emergence caused by T. gallinae in finches in Britain in 2005 is a prime example of the rapid die off of whole populations caused by this single-celled parasite10.

In parasitic combat, T. gallinae is one of the oldest players, with infections in wildlife dating back to the 1500s. This doesn’t mean that T. gallinae is worn out; conversely, it suggests that over time T. gallinae has been honed into a perfect killing machine. It lies in the alimentary tract of birds, and arises to form lesions in the mouths of its hosts. These rice crispy-like inflammations impede the birds from eating and induce dramatic starvation that ultimately leads to the bird’s untimely death. The parasite has an arsenal of cytotoxic mechanisms, including cysteine peptidases and other molecules that damage the target cell plasma membrane, blowing holes in erythrocyte membranes with perforin-like activity.11

Drawing done by Chris Glen of the
University of Queensland.
T. gallinae’s hit list contains a notable creature. The protozoan may be responsible for the devastating destruction and extinction of all dinosaurs. In a recent study done by Wolff et al, the skull of the best preserved fossil of a Tyrannosaurus rex, commonly known as Sue, was examined to determine the most likely cause of the gaping holes on its mandibles. Previously, actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids were suspected as the culprit. However, examination of 10 other prehistoric species with similar markings provided evidence that this avian transmittable protozoan was the cause of the lesions and ultimately starvation due to the severity of the infection. How would a previously unsusceptible beast be taken down by this minute microbe? The answer may lie in the carnivorous slaughter and devouring of infected prey, although this side of the story remains concealed in the distant history of the now inexistent creatures12.

Despite these compelling tales of strife, struggle, and survival in the face of adversity, a winner must be named. Will it be the human parasite T. vaginalis, the leading cause of sexual transmitted infections, or T. gallinae, the avian parasite accused of starving dinosaurs to extinction? Both represent current threats to life on earth, but T. vaginalis delivers a heavy blow to the human population. For the sake of anthropological bias, T. vaginalis walks away with the crown.

Works Cited

1. Petrin D, Delgaty K, Bhatt R, Garber G. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev. 1998 Apr;11(2):300-17.

2. Carlton JM et al . Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science. 2007 Jan 12;315(5809):207-12.

3. Djana F. Harp, Indrajit Chowdhury. Trichomoniasis: evaluation to execution European Journal of  Obstetrics & Gynecology and Reproductive Biology, Volume 157, Issue 1, July 2011, Pages 3–9

4. Isolates of Trichomonas vaginalis concurrently Infected by strains of up to 4 Trichomonasvirus species (Totiviridae). J. Virol. May 2011 vol. 85 no. 9 4258-4270

5. Fichorova RN, Lee Y, Yamamoto HS, Takagi Y, Hayes GR, et al. (2012) Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy. PLoS ONE 7(11): e48418. doi:10.1371/journal.pone.0048418

6. Elisa E. Figueroa-Angulo, Francisco J. Rendón-Gandarilla, Jonathan Puente-Rivera, Jaeson S. Calla-Choque, Rosa E. Cárdenas-Guerra, Jaime Ortega-López, Laura I. Quintas-Granados, M. Elizbeth Alvarez-Sánchez, Rossana Arroyo, The effects of environmental factors on the virulence of Trichomonas vaginalis, Microbes and Infection, Available online 25 September 2012, ISSN 1286-4579, 10.1016/j.micinf.2012.09.004.(

7. D. Provenzano, J.F. Alderete Analysis of human immunoglobulin-degrading cysteine proteinases of Trichomonas vaginalis Infect. Immun., 63 (1995), pp. 3388–3395

8.  Lehker, Biology of Trichomonads. Current Opinion in Infectious Diseases Issue: Volume 13(1), February 2000, pp 37-45

9. J.F. Alderete Iron modulates phenotypic variation and phosphorylation of P270 in double-stranded RNA virus-infected Trichomonas vaginalis Infect. Immun., 67 (1999), pp. 4298–4302

10. Robinson RA, Lawson B, Toms MP, Peck KM, Kirkwood JK, et al. (2010) Emerging Infectious Disease Leads to Rapid Population Declines of Common British Birds. PLoS ONE 5(8): e12215. doi:10.1371/journal.pone.0012215

11. Amin A, Nöbauer K, Patzl M, Berger E, Hess M, et al. (2012) Cysteine Peptidases, Secreted by Trichomonas gallinae, Are Involved in the Cytopathogenic Effects on a Permanent Chicken Liver Cell Culture. PLoS ONE 7(5): e37417. doi:10.1371/journal.pone.0037417

12. Wolff EDS, Salisbury SW, Horner JR, Varricchio DJ (2009) Common Avian Infection Plagued the Tyrant Dinosaurs. PLoS ONE 4(9): e7288. doi:10.1371/journal.pone.0007288

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