Schistosoma mansoni transcriptome project
Links  The cercaria is the stage that infects mammals that come in contact with contaminated fresh water. They are of a definitive sex, and clonal in origin. Thousands of cercariae are produced by a single daughter sporocyst through asexual reproduction of the germ cells. Once mature the cercariae leave the snail into fresh water. Cercariae are about 1 mm in length, and have a characteristic tail that is bifurcated at the end. A thick glycocalyx of about 8.5 nm of thickness is found outside the external membrane and seems to be an adaptation to protect the larva from the hypoostmotic aqueous habitat. The glycocalyx contains 18% amino acid, and 82% carbohydrate, mostly fucose (51%), galactose (30%), and a glycogen-like material The glycocalyx of the tail is not shed during transformation, it is larger, and has a different carbohydrate composition than that of the body. The glycocalyx has been shown to increase parasite survival in animals immunized with it, and in culture inhibits proliferation of blood lymphocytes. The surface tegument of the cercaria does not contain nuclei, ribosomes, and secretory organelles. Cercariae are aerobic organisms, and oxidative metabolism occurs especially in the cercarial tail where enzymes involved in glycogen metabolism are abundantly expressed. Since they are non-feeding organisms that exist largely on glycogen reserves, and must find the vertebrate host within 36-48 hr, or they will die. Upon locating an appropriate host the cercariae penetrates through the skin or mucosa, leaving the tail behind. Penetration is accomplished by attachment to the host’s skin with the oral sucker and with the aid of mucus containing proteolytic enzymes secreted from the post-acetabular glands. Penetration appears to involve both physical force and lytic secretions. Upon entry very distinct morphological changes take place. The cercarial tail is lost, and microvilli appear on the surface, and disappear after about 90 min. Almost immediately after cercarial penetration the glycocalyx is shed with the help of cercarial lytic secretions. The cercarial trilaminate membrane is transformed into a heptalaminate membrane by the apparent fusion of membranous bodies that become more numerous immediately after transformation. The new membrane is completely formed after about 3 hr. Other changes detected during transformation are the switch from mostly aerobic to anaerobic metabolism and an increase in protein phosphorylation, especially of a 14 kDa product . After transformation of cercariae into schistosomula, the larvae proceeds with its maturation and migration in the mammalian host. Schistosomula migrate through the dermis and penetrates into a venule . Migration through the venous system continues through the heart and reaches the lungs about 5 to 5 days post penetration, where the schistosomula pass through the alveolar capillary bed. They have become longer and narrower in the extremities, covered with spines, and their bodies pitted. They are then transported from the lungs to the mesenteric veins in the region of the lower colon, in the case of S. mansoni. It is also thought that the larvae can migrate through the diaphragm and reach the portal vascular system. After 2 weeks most of the worms are found in the liver. No surface pits can be observed, and the convoluted surface forms folds and ridges. Spines and organelles are found mainly on the suckers. At the fourth week of development the surface becomes smoother, and tubercles containing some spines start to develop. The tegument begins to resemble the adult tegument, membranous bodies and discoid bodies are numerous, but mitochondria are smaller and fewer. The gynecophoric canal of the male is developed at this stage, along with sensory organelles. The gynecophoric canal is formed by the lateral edges of the body folding one over the other. The dorsal surface of the lower folding contains large spines that interlocks with the narrower spines of the ventral surface of the upper folding. The ventral surface of the anterior entrance contains short, blunt spines, and a large number of sensory organelles that are associated with the genital pore. The female has broad deep ridges that contain many surface pits. Approximately five weeks after infection most of the worms are approaching maturation and closely resemble the adult worms. The different sexes now mate, complete maturation, and migrate to the mesenteric pelvic veins. The adult worms are about 1 cm in length and are easily recognizable by their two suckers, the oral sucker surrounding the mouth and a ventral sucker or acetabulum. Female schistosomes are dependent on the male for their complete maturation, and contact between the two sexes is necessary for complete sexual development of females. They are in constant association, in the gynaecophoric canal of the male. The female is always slender, cylindrical in shape, and longer than the male. The females display fewer surface spines. There are also differences in physiology, behavior, and antigenic profile between males and females. About 50 to 250 spines composed of actin bundles are located on top of large tegumental tubercles of both males and females. The spines are covered by the outer tegumental membrane and are thought to help anchor the worm in position by pressing against the blood vessel walls. The oral sucker contains spines that point towards the mouth, and is surrounded by sensory papillae. Five morphologically distinct sensory organelles have been described on the outer surface of the worms . The tegument is a syncytium composed of a cytoplasmic layer of about 4 microm thickness connected to cell bodies. The surface membrane is unusual in that it is heptalaminate, formed by two stacked bylaminate membranes, and contains numerous surface pits embedded in the parenchyma of the body. The surface pits are branched and form interconnecting channels, increasing enormously the surface area of the worm. In the cytoplasm, mitochondria, membranous bodies, vesicles, and discoid granules were detected by electron microscopy. Actin microfilaments are responsible for maintaining pit structure, and are also involved in tegumental repair. The content of the carbohydrate rich discoid granules are thought to contribute to the cytoplasm material of the tegument syncytium, and may fuse with the tegumental pits. Multilaminate vesicles, or membranous bodies, probably contribute to the formation of the tegument heptalaminate membrane. The membranes of these organelles consist of a single lipid bilayer. The nuclei of the subtegumental cells are located beneath the muscle layers. They are of irregular shape and can contain more than one nucleus. Common cellular organelles such as golgi bodies, ribosomes, mitochondria, endoplasmic reticulum are also found in the subtegumental cells. Membranous organelles and discoid bodies are also found in these cells, and are thought to be produced by the Golgi. These cell bodies are joined to the tegument by cytoplasmic connections that contain longitudinally organized microtubules. Other Schistosoma species have a similar morphological structure. The surface of S. haematobium contains larger tubercles, the spines are more pronounced, and the surface less pitted. The S. haematobium female contains tubercles without spines. S. japonicum is quite distinct from the previous two species, the males having no tubercles or spines. There are also no pits, except for the anterior and posterior extremities and the surface has microvilli-like projections, which are absent from both extremities where surface pits are found. Small spines can be found on the ventral surface of the gynecophoric canal. Only two types of sensory structures have been observed in S. japonicum. The energy demands of schistosomes are great. Males and females feed on plasma and blood cells. Some digestive enzymes have been characterized, such as a cysteine proteinases (hemoglobinase) and cathepsin B. Adult worms obtain energy by fermentation of glucose to lactic acid, but also by further metabolizing glucose via aeribic respiration. The females consume most of their energy in the production of eggs. The paired male and female are prodigious in this task laying hundreds of eggs daily; up to about 340 eggs per day in mice (about 1 egg every 5 min) for S. mansoni, although it has been noted that fecundity is higher in primates than in mice. Parthenogenesis, the reproduction by the development of an unfertilized gamete, has also been observed in S. mansoni. Egg production is a very elaborate process and commences in average about 30 to 40 days post infection. The length of time between infection and egg deposition is referred to as the prepatent period. Oocytes that will form the egg are first released by the ovary into the oviduct and are fertilized in the seminal gland. The egg moves down the oviduct to the vitelline duct where it is surrounded by approximately 38 vitelline cells. This group of cells moves to the ootype. At this stage granules are released from the vitelline cells, and the liberated material coalesces, in a tanning process, due to crosslinkage by phenol oxidase, that oxidizes tyrosine residues to dehydroxyphenylalanine (DOPA), and the egg shell begins to form. Some proteins that are thought to constitute the eggshell have been identified and cloned. A small family of 4 to 5 genes that share some identity with the insect chorion protein has been identified. These proteins were shown to be produced in extremely high amounts by the vitellaria and comprised of about 44% glycine residues, and 11% tyrosine residues. A second type of protein identified has a higher content of tyrosine residue. The amino acid content of these two proteins, in a 4:1 ratio of glycine rich and tyrosine rich proteins, can account for the observed amino acid content of the eggshell. Finally the egg is released from the uterus and deposited through the gonopore into the lumen of a blood vessel. The eggs are about 114 to 180 micron in length and 45 to 73 micron wide. The egg shell has three layers; an outer microspinous, middle intermediately dense, and an inner dense layer, and contains minute pores that traverse the eggshell. The shell is separated from the miracidium by three layers, Reynold’s, von Lichtenberg’s and the Lehman’s lacuna. The Reynold’s layer is acellular and lies between the basal plasmalemma of von Lichtenberg’s layer and the internal layer of the eggshell. The von Lichtenberg’s layer is formed by a thin epithelium that surrounds the egg contents. The Lehman’s lacuna locates between the embryo and the von Lichtenberg’s layer, and contains lipoid bodies and may contain remains of vitelline cells. The shape of the egg is diagnostic for the most important schistosoma species that infect humans. The eggs of S. mansoni, S. haematobium , and S. japonicum differ in that the first two contain a lateral spine that is rudimentary in the case of S. haematobium, and the latter possesses a terminal spine. Eggs of Schistosoma are passed to the environment through the feces (S. mansoniand S. japonicum) or urine (S. haematobium) of an infected individual. Eggs eliminated from the host with the fecal matter will hatch under the appropriate environmental conditions. Egg hatching is triggered by warm temperatures, low osmolarity water and light conditions (although there are conflicting reports on the effects of light on hatching), that activate the miracidium to break free from the shell. Mature eggs are thought to hatch more easily than immature eggs, and the process happens in the period of a few minutes for most eggs. The process of hatching occurs in the following stages: beating of the flame cells, which are the excretory organs of the organism, repeated and rapid contraction of the whole organism, movement of cilia in the anterior region of the miracidium, and movement of the surface cilia over the entire organism. Both muscle contraction and the action of enzymes are thought to play a role in hatching. It is also thought that an osmotic effect of fresh water aids in hatching due to water absorption into the vacuoles in the miracidium, which increase its size creating pressure on the eggshell. One enzyme that may be involved in this process is a leucine aminopeptidase that is associated with the vitelline membrane. Once the eggshell ruptures in fresh water a miracidium emerges. It is 50 to 180 micron in length and 70 to 80 micron in width. The body is covered by approximately 21 ciliated anucleated cells. On the anterior extremity a structure containing sensory organelles called terebratorium in found. The ducts of the apical gland open in the terebratorium, and the lateral gland opens to the side of it. The posterior part of the body is occupied by about 20 germ cells. The miracidium displays behavioral characteristics of negative geotropism and positive phototropism that assist in intermediate snail host location. The search must be accomplished within 24 hr with the aid of chemoattraction to still unidentified snail substances, after this period the miracidium dies. The intermediate hosts for S. mansoni are snails of the genus Biomphalaria, of the genus Bulinus for S. haematobium, and Oncomelania for S. japonicum. The miracidium penetrates the specific snail host, where higher osmolarity triggers differentiation into sporocysts. The ciliated plates are shed after penetration and, the larva elongates and forms a mother sporocyst containing the germ cells. This process occurs within the foot of the snail. The mother sporocyst is non-motile, the germ cells grow, multiply and transform into daughter sporocysts that mature in 8 to 10 days. Daughter sporocysts then break out and migrate toward the digestive gland of the snail, or hepatopancreas. The daughter sporocysts measure about 100 micron in length and 15 micron width and contain from 50 to 100 germ cells. The daughter sporocysts have a syncytial tegument and an internal tegument surrounding the developing cercariae and organs. The sporocyst can regenerate and for more sporocysts that are able to develop to cercariae. At the snail hepatopancreas the daughter sporocysts grow to non-motile ameboid sacs within which cells bud off from the germinal epithelium and develop into cercariae. The germ cell multiplies during cercariogenesis forming different embryos. The embryo later transform into a morula that develops into germ balls. A primitive epithelium that will form the tegument is developed, and the germ ball constricts into two unequal parts that will develop into the body and tail of the cercaria. This process lasts for about 1 week. Many thousands of cercariae are formed from germ cells in each daughter sporocysts. The cercariae leave the snail into fresh water closing the life cycle. During the life cycle of schistosomes biological variations are displayed at various steps in the life cycle. Emergence of cercariae has been observed to follow a pattern that varies according to the strain studied. This is thought to be of ecological importance, by allowing cercariae to emerge in synchronicity with the behavior of the local vertebrate host and optimizing infection opportunities. As noted for cercariae emergence, eggs also tend to be preferentially eliminated at a certain time of the day. By Guilherme Oliveira Links of interest:  |
