Plasminogen binding proteins in secreted membrane vesicles of Leishmania mexicana

Figuera, Lourdes; Acosta, Héctor; Gómez-Arreaza, Amaranta; Dávila-Vera, Delsy; Balza-Quintero, Alirio; Quiñones, Wilfredo; Mendoza-Briceño, Rosa Virginia; Concepción, Juan Luís; Avilán, Luisana

doi:10.1016/j.molbiopara.2012.11.002

Cited by 17 publications

(12 citation statements)

References 47 publications

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“…We selected FBA for further analysis, since the protein is a Plg-binding protein in several pathogens, as previously described [15,40,70]. To verify if the FBA of Paracoccidioides also has this ability, a recombinant protein was obtained by cloning the cDNA (GenBank Accession Number AY233454) into the expression vector pGEX-4 T-3 (GE Healthcare) as described in Material and Methods.…”

Section: Resultsmentioning

confidence: 99%

“…The release of vesicles to the external environment is used by many pathogens to increase their invasive potential. Vesicles contain many virulence factors, including molecules that bind to and activate Plg [27,70,75]. The presence of FBA at the surface and vesicle of the fungus can allow the capture of hPlg and plasmin generation, forming a highly fibrinolytic layer around the fungal cell.…”

Section: Resultsmentioning

confidence: 99%

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Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein

et al. 2015

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BackgroundDespite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to plasminogen.ResultsIn the present study, we employed proteomic analysis of the secretome, in order to identify plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome, presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA. These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/dissemination of Paracoccidioides.ConclusionsThese data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might be involved somehow in the processes of invasion and spread of the fungus during infection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein

et al. 2015

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“…Plasmin produced by plasminogen activation can degrade fibrin networks and different proteins of the extracellular matrix [13], elements that could entail a barrier in the migration of parasites through the host tissues. The ability of AsL3 to enhance plasmin generation could be used by the parasite as a survival mechanism allowing it to degrade these components in order to facilitate its migration through the host tissues, as it has been postulated for other pathogens [27,31,[33][34][35][36]. Regarding other survival-related functions, the degradation of proteins for nutrition, or of immunoglobulins and complement components for immune evasion mechanisms have also been suggested to be the result of the interaction between pathogens and the fibrinolytic system of their hosts [10].…”

Section: Discussionmentioning

confidence: 99%

Pro-fibrinolytic potential of the third larval stage of Ascaris suum as a possible mechanism facilitating its migration through the host tissues

et al. 2020

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Background: Ascaris roundworms are the parasitic nematodes responsible for causing human and porcine ascariasis. Whereas A. lumbricoides is the most common soil-transmitted helminth infecting humans in the world, A. suum causes important economic losses in the porcine industry. The latter has been proposed as a model for the study of A. lumbricoides since both species are closely related. The third larval stage of these parasites carries out an intriguing and complex hepatopulmonary route through the bloodstream of its hosts. This allows the interaction between larvae and the physiological mechanisms of the hosts circulatory system, such as the fibrinolytic system. Parasite migration has been widely linked to the activation of this system by pathogens that are able to bind plasminogen and enhance plasmin generation. Therefore, the aim of this study was to examine the interaction between the infective third larval stage of A. suum and the host fibrinolytic system as a model of the host-Ascaris spp. relationships. Methods: Infective larvae were obtained after incubating and hatching fertile eggs of A. suum in order to extract their cuticle and excretory/secretory antigens. The ability of both extracts to bind and activate plasminogen, as well as promote plasmin generation were assayed by ELISA and western blot. The location of plasminogen binding on the larval surface was revealed by immunofluorescence. The plasminogen-binding proteins from both antigenic extracts were revealed by two-dimensional electrophoresis and plasminogen-ligand blotting, and identified by mass spectrometry. Results: Cuticle and excretory/secretory antigens from infective larvae of A. suum were able to bind plasminogen and promote plasmin generation in the presence of plasminogen activators. Plasminogen binding was located on the larval surface. Twelve plasminogen-binding proteins were identified in both antigenic extracts. Conclusions: To the best of our knowledge, the present results showed for the first time, the pro-fibrinolytic potential of infective larvae of Ascaris spp., which suggests a novel parasite survival mechanism by facilitating the migration through host tissues.

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“…Enolase, a ubiquitous metabolic enzyme binds to plasminogen as a unique example of a multifunctional protein [ 33 ]. Promastigotes appear to secrete enolase in exocytic vesicles, which can help in immune evasion [ 34 ], since these vesicles have been implicated in parasite-macrophage communication. Furthermore, plasminogen-associated vesicles can trap macrophages, potentially allowing parasites to move further into the dermis.…”

Section: Interaction Between Leishmania and Host Ementioning

confidence: 99%

The site of the bite: Leishmania interaction with macrophages, neutrophils and the extracellular matrix in the dermis

2016

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Leishmania spp., the causative agents of leishmaniasis, are intracellular parasites, transmitted to humans via the bite of their sand fly vectors. Once inoculated, the promastigotes are exposed to the dermis, which is composed of extracellular matrix (ECM), growth factors and its resident cells. Promastigote forms are phagocytosed by macrophages recruited to the site of the sand fly bite, either directly or after interaction with neutrophils. Since Leishmania is an intracellular parasite, its interaction with the host ECM has been neglected as well as the immediate steps after the sand fly bite. However, promastigotes must overcome the obstacles presented by the dermis ECM in order to establish the infection. Thus, the study of the interaction between Leishmania promastigotes and ECM components as well as the earliest stages of infection are important steps to understand the establishment of the disease, and could contribute in the future to new drug developments towards leishmaniasis.

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Plasminogen binding proteins in secreted membrane vesicles of Leishmania mexicana

Cited by 17 publications

References 47 publications

Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein

Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein

Pro-fibrinolytic potential of the third larval stage of Ascaris suum as a possible mechanism facilitating its migration through the host tissues

The site of the bite: Leishmania interaction with macrophages, neutrophils and the extracellular matrix in the dermis

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