Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system
Abstract Plasmin, the final product of fibrinolysis, is a broad-spectrum serine protease that degrades extracellular matrix (ECM) components, a function exploited by multiple pathogens for dissemination purposes. The trematode Fasciola hepatica is the leading cause of fasciolosis, a major disease of...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s13567-025-01449-4 |
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| author | Judit Serrat María Torres-Valle Carolina De Marco Verissimo Mar Siles-Lucas Javier González-Miguel |
| author_facet | Judit Serrat María Torres-Valle Carolina De Marco Verissimo Mar Siles-Lucas Javier González-Miguel |
| author_sort | Judit Serrat |
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| description | Abstract Plasmin, the final product of fibrinolysis, is a broad-spectrum serine protease that degrades extracellular matrix (ECM) components, a function exploited by multiple pathogens for dissemination purposes. The trematode Fasciola hepatica is the leading cause of fasciolosis, a major disease of livestock and an emerging zoonosis in humans. Infection success depends on the ability of F. hepatica newly excysted juveniles (FhNEJ) to penetrate the host intestinal wall, a process that remains incompletely understood. We have previously shown that FhNEJ are capable of binding plasminogen (PLG), the zymogen of plasmin, on their tegument surface, which leads to plasmin generation in the presence of host-derived PLG activators and subsequent degradation of laminin, a major component of the intestinal ECM. Here, we describe the interaction between a tegument extract of FhNEJ and the precursor of the urokinase-type PLG activator (pro-u-PA). We found that F. hepatica cathepsins B3, L3, enolase and glutathione S-transferase mediate this interaction, suggesting a multifactorial or moonlighting role for these proteins. Additionally, our results revealed that the tegument of FhNEJ contains a protease that is capable of cleaving and activating pro-u-PA into its catalytically active form, which positively impacts the capacity of the parasites to generate plasmin from the host PLG. Collectively, our findings indicate that FhNEJ interact with the host fibrinolytic system at multiple levels, reinforcing the potential of targeting this interaction as a strategy to prevent FhNEJ trans-intestinal migration and infection success. |
| format | Article |
| id | doaj-art-74d17b5d71ae4faf9318cb9a89239a25 |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-74d17b5d71ae4faf9318cb9a89239a252025-01-26T12:47:49ZengBMCVeterinary Research1297-97162025-01-0156111410.1186/s13567-025-01449-4Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic systemJudit Serrat0María Torres-Valle1Carolina De Marco Verissimo2Mar Siles-Lucas3Javier González-Miguel4Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC)Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC)Molecular Parasitology Laboratory, University of GalwayLaboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC)Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC)Abstract Plasmin, the final product of fibrinolysis, is a broad-spectrum serine protease that degrades extracellular matrix (ECM) components, a function exploited by multiple pathogens for dissemination purposes. The trematode Fasciola hepatica is the leading cause of fasciolosis, a major disease of livestock and an emerging zoonosis in humans. Infection success depends on the ability of F. hepatica newly excysted juveniles (FhNEJ) to penetrate the host intestinal wall, a process that remains incompletely understood. We have previously shown that FhNEJ are capable of binding plasminogen (PLG), the zymogen of plasmin, on their tegument surface, which leads to plasmin generation in the presence of host-derived PLG activators and subsequent degradation of laminin, a major component of the intestinal ECM. Here, we describe the interaction between a tegument extract of FhNEJ and the precursor of the urokinase-type PLG activator (pro-u-PA). We found that F. hepatica cathepsins B3, L3, enolase and glutathione S-transferase mediate this interaction, suggesting a multifactorial or moonlighting role for these proteins. Additionally, our results revealed that the tegument of FhNEJ contains a protease that is capable of cleaving and activating pro-u-PA into its catalytically active form, which positively impacts the capacity of the parasites to generate plasmin from the host PLG. Collectively, our findings indicate that FhNEJ interact with the host fibrinolytic system at multiple levels, reinforcing the potential of targeting this interaction as a strategy to prevent FhNEJ trans-intestinal migration and infection success.https://doi.org/10.1186/s13567-025-01449-4Fasciola hepaticanewly excysted juvenilespro-urokinasefibrinolytic systemhost‒parasite interactions |
| spellingShingle | Judit Serrat María Torres-Valle Carolina De Marco Verissimo Mar Siles-Lucas Javier González-Miguel Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system Veterinary Research Fasciola hepatica newly excysted juveniles pro-urokinase fibrinolytic system host‒parasite interactions |
| title | Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| title_full | Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| title_fullStr | Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| title_full_unstemmed | Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| title_short | Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| title_sort | binding and cleavage of pro urokinase by a tegument extract of fasciola hepatica newly excysted juveniles activate the host fibrinolytic system |
| topic | Fasciola hepatica newly excysted juveniles pro-urokinase fibrinolytic system host‒parasite interactions |
| url | https://doi.org/10.1186/s13567-025-01449-4 |
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