1. Introduction

#### 1.1. Giardia and giardiasis

Giardia was observed for the first time by Antony Van Leeuwenhoek in 1681, but it was Lambl who described the cell morphological characteristics in detail and named it Cercomonas intestinalis. Subsequently, Blanchard changed the nomenclature in 1888 to Giardia lamblia [1–3]. The parasite is also known as Giardia intestinalis, Giardia duodenalis, Giardia enterica and Lamblia intestinalis. Currently, the preferred name is G. intestinalis.

The trophozoite of G. intestinalis inhabits the small intestine and causes the disease, whereas the cyst is protected by a cyst wall, can survive in adverse environmental conditions and thus is responsible for parasite transmission. Giardiasis starts when the cysts are ingested via food or contaminated water and reach the small intestine. The trophozoites emerge from the cyst wall and colonize the intestinal epithelium [4]. The emerged trophozoites adhere and spread out by binary divisions and form a monolayer over the intestinal mucosa provoking local inflammation and reduction in nutrient uptake. The parasites may reach the final portions of the intestine, becoming a cyst again, and they are liberated with the feces. The cysts can then infect new hosts [4]. Diarrhea is the main symptom of G. intestinalis infection, and giardiasis occurs in humans and several animals throughout the world. Giardial transmission between different species is frequent, and this characterizes giardiasis as a zoonotic disease [5]. The infection rates of giardiasis are associated with sanitary conditions since low rates are observed when sanitary conditions are implemented [6]. Giardiasis mainly affects children and is considered a cosmopolite disease [7]. Several factors such as geographic area, group of analysis, sensitivity of the diagnostic methods and health care accessibility influence the prevalence rates reported [8]. The disease treatment is based in nitroimidazole-derived drugs (metronidazole, tinidazole and ornidazole), since metronidazole is the most widely used drug [9].

## 2. Endomembrane system

The endomembrane system of higher eukaryotes comprises of a number of structures, such as the endoplasmic reticulum, nucleus, Golgi, lysosomes, peroxisomes, autophagosomes and vesicles involved in different traffic pathways. Many theories have addressed the evolutionary origin of eukaryotic membranes; the most acceptable one is the invagination of plasma membrane, which is based on the similarity between the endoplasmic reticulum (ER) lumen to the environment [10, 11].

Although Giardia belongs to the eukaryotic group, it lacks some of the typical organelles found in eukaryotes; therefore, this parasite is an interesting model to study cell evolution. Mitochondria and peroxisomes are not present in this parasite, as found in morphological and biochemical studies. In addition, Golgi complex and vesicles of the endocytic pathway are incipient. On the other hand, Giardia trophozoites exhibit membrane structures that incorporate the cationic, membrane potential-sensitive fluorophore rhodamine 123 and reduce a tetrazolium fluorogen. Based on this observation, the existence of membrane-associated sites with some similarities to

Figure 1. Endomembrane system of G. intestinalis. Schemes of a Giardia trophozoite (a) and when the process of encystation starts (b). Parasites present two nuclei. Both encystation vesicles ESV (encystation specific vesicle) and ECV (encystation carbohydrate-positive vesicle) are only present in the encysting cell. The ESVs are larger and dense, while the ECVs are smaller and lighter (b).

mitochondria has been suggested; an aerobic flagellate presenting mitochondria was proposed to possibly be the ancestor of G. intestinalis [12].

The membrane system of G. intestinalis comprises a unique set of vesicles named peripheral vesicles and a much diffused endoplasmic reticulum network. Moreover, this cell possesses two nuclei with a very similar nuclear membrane complex as observed in higher eukaryote cells (Figure 1a). During the differentiation of trophozoite to cysts, two types of membranebounded vesicles appear, the ESVs and ECVs, and both act to build the cyst wall, which is a constitutive and important structure of cyst (Figure 1b). Deeper in the encystation process, we face a paradigm: is there a Golgi-like structure in Giardia? Some authors claimed that during the encystation process, the ESVs assume some Golgi characteristics [13].

Below, we will discuss each of the membrane-bounded structures that compose the endomembrane system of G. intestinalis (Figure 1).
