Moonlighting on the Fasciola hepatica tegument: Enolase, a glycolytic enzyme, interacts with the extracellular matrix and fibrinolytic system of the host.

Autor: O'Kelly E; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., Cwiklinski K; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., De Marco Verissimo C; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., Calvani NED; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., López Corrales J; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., Jewhurst H; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., Flaus A; Centre for Chromosome Biology, School of Natural Science, University of Galway, H91 TK33 Galway, Ireland., Lalor R; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., Serrat J; Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC), Salamanca, Spain., Dalton JP; Molecular Parasitology Laboratory, University of Galway, Galway, Republic of Ireland., González-Miguel J; Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC), Salamanca, Spain.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Aug 30; Vol. 18 (8), pp. e0012069. Date of Electronic Publication: 2024 Aug 30 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012069
Abstrakt: Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary 'moonlighting' functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of ~94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impede this function by vaccination or drug design.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 O’Kelly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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