The Metamorphosis of Giardia lamblia

By AK

Evolution is often cited as the core of biology but it has also been exhausted in various media outlets from television to newspapers and books. One very popular children’s television program, Pokémon, shows many of the organisms known as Pokémon “evolving” into different forms which acquire a wide array of new abilities that make them more successful than their previous forms. Understandably, much of the actual scientific meaning of evolution is lost in the show, but the concept of turning into a new form with new abilities often holds true in science. In this sense, the way the Pokémon “evolve” into another form is actually a metamorphosis rather than evolution as is known in the scientific context. One prime example, Giardia lamblia, also known as Giardia intestinallis or Giardia duodenalis, is a protozoan whose human infection life cycle revolves around the metamorphosis from the cyst form into the trophozoite form (Figure 1).

G. lamblia was first discovered in the seventeenth century and became relevant in the United States and Europe in the 1960s and 1970s (2). Transmission often occurs by ingesting food or water contaminated with G. lamblia cysts but can also spread directly through the fecal-oral pathway which is characteristic of poor hygiene practices (2). One very unique feature of giardiasis, or the infection with G. lamblia, is that the infectious G. lamblia trophozoites are confined strictly to the lumen of the small intestine which does not spread to the blood stream like many other protozoan infections (1). Due to the specific localization of this infection to the small intestine, the major symptoms associated with giardiasis include severe, watery diarrhea and stomach cramps. It is now cited as the leading cause for waterborne diarrhea in the United States (2). Approximately 5,000 people are hospitalized annually in the US and millions of cases are reported world-wide (2). One of the most effective medications against giardiasis is metronidazole, which is a nitroimidaozole antibiotic medication (2). One of the key elements of this drug and how it avoids harming human cells, is that it attacks the anaerobic pathways in G. lamblia which are essential for the protozoan’s survival. In giardiasis, this drug ultimately damages the DNA of the infectious trophozoite stage of infection and kills the protozoan before it completes its life cycle and damages the host.

Figure 1: G.lamblia life cycle.

The life cycle of G. lamblia can be split into two distinct phases; the dormant, cyst phase and the infectious, trophozoite phase. The cysts of G. lamblia have been shown to be extremely resilient to a wide variety of environmental conditions and also have a metabolic rate of just ten to twenty percent of the trophozoite form allowing them to survive for extended periods outside of their hosts. This begs the question as to how the cyst form of G. lamblia “evolves” into the trophozoite form so quickly in the human host intestine. The first step in human infection is ingesting the resilient cysts (only 10 required for infection) through contaminated water or food as stated above (2). Thereafter, the cysts have to travel through the digestive tract, avoiding degradation till they reach the small intestine. There have been several studies regarding the metamorphosis phenomenon which have found that the shift in pH from the acidic stomach to the slightly alkaline pH of the small intestine serves as a signal to alter the morphology and gene expression of the cyst which results in the formation of trophozoites (4). Hetsko et. al. found that it was likely that there was pre-made mRNA ready to be  translated when the cysts were exposed to the varying physiological pH transitions, which may encode for a variety of surface proteins such as adhesive molecules for localization in the small intestine (4). This “evolution” of the cyst form of G. lamblia to the trophozoite is termed excystation or encystation depending on the stage of infection (Figure 1).

After “evolving” into the infectious trophozoite form due to the various pH signals in the digestive tract, they start causing symptoms in individuals by localizing to the duodenum and the upper intestine (2). Symptoms such as watery diarrhea, excessive flatulence, greasy stools, stomach cramps, and bloating are some of the most common symptoms associated with giardiasis (1). However, it should be noted that giardiasis can be asymptomatic in people with strong immune systems and usually causes very severe symptoms only in immunocompromised individuals. It is hypothesized that the colonization of G. lamblia in the small intestine results in disease due to a variety of mechanisms such as: by the direct damage of the human intestinal mucosa, through the release of cytopathic substances from the trophozoites, and/or that an immune response that results in the  inflammation of the mucosa cells (2)(3). Finally the trophozoites’ extended stay in an alkaline pH in the small intestine also serves as a signal for the encystation process which triggers metamorphosis back into the dormant cyst form which are excreted through the large intestine and ultimately in the feces circling back to the first stage of the G. lamblia life cycle (2)(4).

Just as Pokémon “evolve” into different forms with different characteristics, Giardia lamblia metamorphoses from its dormant, cyst form to an infectious, trophozoite form by sensing sudden physiological pH changes seen in the digestive tract. This metamorphosis event is vital for the protozoa to cause disease in humans and ultimately complete its life cycle. Further understanding of this mechanism of metamorphosis can be vital in furthering treatment and prevention of this disease.

References

1)     Gardner, T., & Hill, D. (2001). Treatment of Giardiasis. Clinical Microbiology Review. 14 (1): 114-128.

2)     Adam, R. (2001). Biology of Giardia lamblia. Clinical Microbiology Review. 14 (3): 447-475.

3)     Faubert,G.(2000). Immune Response to Giardia duodenalis. Clinical Microbiology Review. 13 (1): 35-54.

4)     Hetsko, M., McCaffery, J., Svard, S., Meng, T., Que, X., and Gillian, F. (1998). Cellular and Transcriptional Changes During Excystation of Guard lamblia in vitro. 88 (3): 172-183.