The saposin-like proteins 1, 2, and 3 of Fasciola gigantica

Grams, Rudi; Adisakwattana, Poom; Ritthisunthorn, Nonglucksanawan; Eursitthichai, Veerachai; Vichasri-Grams, Suksiri; Viyanant, Vithoon

doi:10.1016/j.molbiopara.2006.03.007

Cited by 20 publications

(20 citation statements)

References 30 publications

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“…This protein, which was termed FhSAP-2 because of its similarity to a saposin-like protein family and the amoebapore precursors of Entamoeba histolytica, has been implicated in the penetration and lysis of ingested host red blood cells not only in Fasciola (29,30) but also in other helminths (39). Saposin-like molecules are likely secreted from granules within cells lining the parasite esophagus so that ingested red blood cells are lysed as soon as they enter the digestive track.…”

Section: Discussionmentioning

confidence: 99%

“…From the detailed annotations of the 160 adult secreted proteins the predominance of cathepsin L cysteine proteases is clearly evident as these are represented by a total of 66 (41.2%) proteins (Table II and supplemental Table 1 The next most abundant secreted protein based on the number of ESTs identified was saposin-like protein 3 that has been reported as a secreted protein by Grams et al (29) and suggested to play a role in red blood cell lysis (30). Other proteins of interest to our study include several novel cathepsin B cysteine endoproteases (designated cathepsins B4 -B10 in the current study), four novel asparaginyl endopeptidases or legumains (designated legumains 4 -7 in the current study), and a cysteine protease inhibitor, cystatin.…”

Section: Transcriptomicsmentioning

confidence: 99%

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An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola hepatica

Robinson

Menon

Donnelly

et al. 2009

Molecular & Cellular Proteomics

248

249

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To infect their mammalian hosts, Fasciola hepatica larvae must penetrate and traverse the intestinal wall of the duodenum, move through the peritoneum, and penetrate the liver. After migrating through and feeding on the liver, causing extensive tissue damage, the parasites move to their final niche in the bile ducts where they mature and produce eggs. Here we integrated a transcriptomics and proteomics approach to profile Fasciola secretory proteins that are involved in host-pathogen interactions and to correlate changes in their expression with the migration of the parasite. Prediction of F. hepatica secretory proteins from 14,031 expressed sequence tags (ESTs) available from the Wellcome Trust Sanger Centre using the semiautomated EST2Secretome pipeline showed that the major components of adult parasite secretions are proteolytic enzymes including cathepsin L, cathepsin B, and asparaginyl endopeptidase cysteine proteases as well as novel trypsinlike serine proteases and carboxypeptidases. Proteomics analysis of proteins secreted by infective larvae, immature flukes, and adult F. hepatica showed that these proteases are developmentally regulated and correlate with the passage of the parasite through host tissues and its encounters with different host macromolecules. Proteases such as FhCL3 and cathepsin B have specific functions in larvae activation and intestinal wall penetration, whereas FhCL1, FhCL2, and FhCL5 are required for liver penetration and tissue and blood feeding. Besides proteases, the parasites secrete an array of antioxidants that are also highly regulated according to their migration through host tissues. However, whereas the proteases of F. hepatica are secreted into the parasite gut via a classical endoplasmic reticulum/Golgi pathway, we speculate that the antioxidants, which all lack a signal sequence, are released via a non-classical trans-tegumental pathway. Fasciola hepatica is a helminth (worm) parasite with a worldwide distribution. Although traditionally regarded as a parasite of livestock, particularly sheep and cattle, that results in a large economic loss to the agricultural community it has recently emerged as an important human infection in many regions of the world, including South America, Iran, Egypt, and mainland South-East Asia (1). Dormant larvae contained within cysts adhere to vegetation and emerge as infective juveniles (newly excysted juveniles (NEJs)) 1 in the duodenum following ingestion by animals or humans. They infect their hosts by rapidly penetrating the intestinal wall and entering the peritoneal cavity where they break through the liver capsule. After 8 -12 weeks of consistent burrowing, feeding, and growth within the liver parenchyma they move to their final destination within the bile ducts where they mature and produce enormous numbers of eggs (2). The two distinct clinical phases of fasciolosis are directly related to the migration of the parasites: acute fasciolosis, which manifests as fever, abdominal pain, weight loss, and hepatomegaly, is associated with...

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Section: Discussionmentioning

confidence: 99%

Section: Transcriptomicsmentioning

confidence: 99%

An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola hepatica

Robinson

Menon

Donnelly

et al. 2009

Molecular & Cellular Proteomics

248

249

View full text Add to dashboard Cite

show abstract

“…The identification of such molecules could represent specific markers for the detection of F. hepatica. In this context, several molecules present in ESP have been characterized, including the cathepsin family of cysteine proteases (11), CuZn superoxide dismutase (25,43), enolase (5,24), fatty acid binding proteins (21), glutathione S-transferases (9,64), leucine aminopeptidase (LAP) (1), saposin-like molecules (15,19,48), and thioredoxin-associated proteins (23,24,29,32,36,51,52,56,57).…”

mentioning

confidence: 99%

Leucine Aminopeptidase Is an Immunodominant Antigen of Fasciola hepatica Excretory and Secretory Products in Human Infections

Marcilla

Rubia

Sotillo

et al. 2008

Clin Vaccine Immunol

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The liver fluke Fasciola hepatica parasitizes humans and ruminant livestock worldwide, and it is now being considered a reemerging zoonotic disease, especially in areas in which it is endemic, such as South America. This study investigates the immune response to excretory and secretory products produced by F. hepatica in a group of patients from the Peruvian Altiplano, where the disease is highly endemic. Using a proteomic approach and immunoblotting techniques, we have identified the enzymes leucine aminopeptidase (LAP) and phosphoenolpyruvate carboxykinase as immunodominant antigens recognized by sera from fasciolosis patients. An indirect enzyme-linked immunosorbent assay using recombinant LAP as the antigen was developed to check sera from individuals of this region. Our results demonstrate that LAP produces a specific and strong reaction, suggesting its potential use in the serologic diagnosis of F. hepatica infections in humans.

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“…The last can result in disruption of the target cells as observed in the activities against the foreign cells by human granulysin, porcine NK-lysin, and Entamoeba amoebapores. In Fasciola spp., two and three SAPLIP encoding genes were cloned from F. hepatica (Reed et al 2000;Espino and Hillyer 2003) and Fasciola gigantica (Grams et al 2006), respectively. The genes showed closed relationship to amoebapores of Entamoeba spp., suggesting their roles in the cytolysis of target cells.…”

Section: Introductionmentioning

confidence: 99%

“…Different isotypes of SAPLIPs were differentially expressed in different stages of the parasites' life cycles within the definitive host. In F. gigantica, FgSAP-1 gene was expressed in newly excysted juvenile (NEJ) and early juvenile parasites, whereas FgSAP-2 and FgSAP-3 genes were expressed in juvenile and adult parasites (Grams et al 2006). Although the activity of juvenile-specific FgSAP-1 has not yet been demonstrated, it is believed that various types of host cells, including erythrocytes, PMBCs, intestinal epithelial cells, connective tissue cells, and hepatocytes, are the possible targets as the parasites are migrating through the intestinal wall and peritoneal cavity to the liver, and finally to the bile duct.…”

Section: Introductionmentioning

confidence: 99%

Characterization and localization of saposin-like protein-2 (SAP-2) in Fasciola gigantica

et al. 2010

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Fasciola gigantica saposin-like protein-2 (FgSAP-2) belongs to a family of lipid-interacting proteins that are involved in the cytolysis of target cells. In this study, we have cloned and expressed FgSAP-2 and produced the antibody against this recombinant protein. Rabbit antiserum against rFgSAP-2 reacted with a similar native protein in the whole body extracts of the 4-week-old juvenile and adult stage, as well as a protein in their excretion-secretion, but not in the tegument. In situ hybridization and immunofluorescence detection revealed the presence of SAP-2 mRNA transcripts and proteins in the cecal epithelial cells of 4-week-old juvenile and adult parasites, but not in the metacercariae and newly excysted juveniles. Moreover, SAP-2 is present only in the cecal epithelial cells lining the distal part of the digestive tract, but not in the tegumental-type epithelium lining the proximal part of the digestive tract. The rFgSAP-2 reacted with antisera from rabbits infected with F. gigantica metacercariae collected at 5 weeks, but not at 2 weeks after infection. Anti-rFgSAP-2 did not exhibit any cross-reactivity with the other parasites' antigens, including Opisthorchis viverrini, Eurytrema pancreaticum, Cotylophoron cotylophorum, Fischoederius cobboldi, Gigantocotyle explanatum, Paramphistomum cervi, Setaria labiato-papillosa, and Haemonchus placei. This finding indicated that SAP-2 is a unique protein that is expressed only in late juvenile and adult F. gigantica, and it could be considered for immunodiagnostic and as a vaccine candidate for fasciolosis.

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The saposin-like proteins 1, 2, and 3 of Fasciola gigantica

Cited by 20 publications

References 30 publications

An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola hepatica

An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola hepatica

Leucine Aminopeptidase Is an Immunodominant Antigen of Fasciola hepatica Excretory and Secretory Products in Human Infections

Characterization and localization of saposin-like protein-2 (SAP-2) in Fasciola gigantica

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