A distinctive repertoire of cathepsins is expressed by juvenile invasive Fasciola hepatica

Cancela, Mario; Acosta, Daniel; Rinaldi, Gabriel; Silva, Edileusa; Durán, Rosario; Roche, Leda; Zaha, Arnaldo; Carmona, Carlos; Tort, José F.

doi:10.1016/j.biochi.2008.04.020

Cited by 85 publications

(79 citation statements)

References 68 publications

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“…It also supported the lack of expression of clades FhCL3 and FhCL4 in adult parasites, although proteases encoding these genes are expressed by NEJs (see below and Ref. 28). We also identified five novel cathepsin L proteases that although encoded by partial nucleotide sequences (contigs 1553, 2626, and 1886 and singletons Fhep55b05.q1k and Fhep18b10.q1k) may represent a new phylogenetic cluster.…”

Section: Discussionmentioning

confidence: 55%

“…Earlier studies by Tkalcevic et al (34) using N-terminal sequencing to identify proteins expressed by larvae reported a sequence of a cathepsin L cysteine protease that we now know matches exactly with the predicted N terminus of FhCL3_nl22 (56). More recently, Cancela et al (28) confirmed the restricted expression of FhCL3 and another protease, FhCL4, to infective larvae by isolating cDNAs encoding these enzymes from a F. hepatica larvae-specific cDNA library and subsequently by using RT-PCR expression analysis. No FhCL4 peptides were identified in the present analysis suggesting that this enzyme may be expressed at low levels, performs specific intracellular functions, and is not secreted by F. hepatica.…”

Section: Proteomics Analysis Of the Dormant And Infective Stagementioning

confidence: 81%

“…28). All three cathepsin B proteases were identified in intense protein bands that migrated in reducing SDS-PAGE at molecular masses of ϳ36 -50 kDa and ϳ50 -70 kDa (Fig.…”

Section: Proteomics Analysis Of the Dormant And Infective Stagementioning

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

247

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: 55%

Section: Proteomics Analysis Of the Dormant And Infective Stagementioning

confidence: 81%

See 1 more Smart Citation

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

Robinson

Menon

Donnelly

et al. 2009

Molecular & Cellular Proteomics

247

249

View full text Add to dashboard Cite

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“…Later, three cathepsin B isotypes were identified from stage-specific cDNA libraries of F. gigantica and named FgCatB1, FgCatB2, and FgCatB3 (Meemon et al 2004). The orthologous cathepsin B isotypes (CB1, CB2, CB3) were then identified in juvenile F. hepatica (Cancela et al 2008(Cancela et al , 2010. RT-PCR and phylogenetic analyses demonstrated that these isotypes were stagespecific (Meemon et al 2004;Cancela et al 2008;Smooker et al 2010).…”

Section: Cathepsin Bmentioning

confidence: 99%

“…Cathepsin B-like proteases have been demonstrated to be one of the major proteases synthesized by newly excysted juvenile (NEJ) and immature Fasciola parasites (Tkalcevic et al 1995;Wilson et al 1998;Law et al 2003;Meemon et al 2004;Cancela et al 2008). The first cathepsin B of Fasciola spp.…”

Section: Cathepsin Bmentioning

confidence: 99%

Juvenile-specific cathepsin proteases in Fasciola spp.: their characteristics and vaccine efficacies

Meemon

Sobhon

2015

Parasitol Res

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Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is one of the most neglected tropical zoonotic diseases. One sustainable control strategy against these infections is the employment of vaccines that target proteins essential for parasites' invasion and nutrition acquiring processes. Cathepsin proteases are the most abundantly expressed proteins in Fasciola spp. that have been tested successfully as vaccines against fasciolosis in experimental as well as large animals because of their important roles in digestion of nutrients, invasion, and migration. Specifically, juvenile-specific cathepsin proteases are the more effective vaccines because they could block the invasion and migration of juvenile parasites whose immune evasion mechanism has not yet been fully developed. Moreover, because of high sequence similarity and identity of cathepsins from juveniles with those of adults, the vaccines can attack both the juvenile and adult stages. In this article, the characteristics and vaccine potentials of juvenile-specific cathepsins, i.e., cathepsins L and B, of Fasciola spp. were reviewed.

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Prospects for Immunoprophylaxis Against Fasciola hepatica (Liver Fluke)

Spithill

Carmona

Piedrafita

et al. 2012

Parasitic Helminths

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A distinctive repertoire of cathepsins is expressed by juvenile invasive Fasciola hepatica

Cited by 85 publications

References 68 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

Juvenile-specific cathepsin proteases in Fasciola spp.: their characteristics and vaccine efficacies

Prospects for Immunoprophylaxis Against Fasciola hepatica (Liver Fluke)

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