Proteomics

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Proteomic analysis of Fasciola hepatica somatic proteome and secretome


ABSTRACT: Background The parasite Fasciola hepatica infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Results Transcriptome and proteome analysis of F. hepatica metacercariae and NEJ revealed the rapidity and multitude of metabolic and developmental alterations this parasite undergoes to accomplish infection. We show that metacercariae are metabolically active, contrary to the view that this stage is dormant. Following ingestion, the NEJ expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new increasingly anaerobic environment. Temperature increases induce neoblast proliferation and the remarkable up-regulation of genes associated with growth and development. Cysteine proteases synthesised by gastrodermal cells are secreted to facilitate invasion and tegumental transporters are varied to deal with osmotic/salinity changes. Major proteins of the total NEJ secretome include proteases, proteases inhibitors, anti-oxidants as well as an array of immunomodulators that likely disarm host innate immune effector cells. Conclusions The challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion that facilitate growth, development and maturation. Our molecular analysis of the critical process of host invasion has identified key targets for future drug and vaccine strategies directed at preventing parasite infection.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Fasciola Hepatica (liver Fluke)

TISSUE(S): Whole Body

DISEASE(S): Disease Free

SUBMITTER: Krystyna Cwiklinski  

LAB HEAD: John P Dalton

PROVIDER: PXD007255 | Pride | 2018-03-26

REPOSITORIES: Pride

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Publications

Infection by the Helminth Parasite <i>Fasciola hepatica</i> Requires Rapid Regulation of Metabolic, Virulence, and Invasive Factors to Adjust to Its Mammalian Host.

Cwiklinski Krystyna K   Jewhurst Heather H   McVeigh Paul P   Barbour Tara T   Maule Aaron G AG   Tort Jose J   O'Neill Sandra M SM   Robinson Mark W MW   Donnelly Sheila S   Dalton John P JP  

Molecular & cellular proteomics : MCP 20180110 4


The parasite <i>Fasciola hepatica</i> infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Here, transcriptome and proteome analysis of <i>ex vivo F. he  ...[more]

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