Interaction of Leishmania mexicana promastigotes with the plasminogen–plasmin system

Avilán, Luisana; Calcagno, Marina; Figuera, Mariana; Lemus, Leticia; Puig, Juan; Rodrı́guez, Ana

doi:10.1016/s0166-6851(00)00269-3

Cited by 34 publications

(24 citation statements)

References 36 publications

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“…The proteins and protein fragments that did not bind to any procyclic promastigote as determined by SPRi are listed in Table S3 in the supplemental material. Plasminogen was spotted onto the arrays as a positive control because it has been reported previously to bind to Leishmania (27). Indeed, all Leishmania strains tested in this study bound to plasminogen ( Fig.…”

Section: Resultsmentioning

confidence: 75%

Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging

et al. 2014

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We have set up an assay to study the interactions of live pathogens with their hosts by using protein and glycosaminoglycan arrays probed by surface plasmon resonance imaging. We have used this assay to characterize the interactions of Leishmania promastigotes with ϳ70 mammalian host biomolecules (extracellular proteins, glycosaminoglycans, growth factors, cell surface receptors). We have identified, in total, 27 new partners (23 proteins, 4 glycosaminoglycans) of procyclic promastigotes of six Leishmania species and 18 partners (15 proteins, 3 glycosaminoglycans) of three species of stationary-phase promastigotes for all the strains tested. The diversity of the interaction repertoires of Leishmania parasites reflects their dynamic and complex interplay with their mammalian hosts, which depends mostly on the species and strains of Leishmania. Stationary-phase Leishmania parasites target extracellular matrix proteins and glycosaminoglycans, which are highly connected in the extracellular interaction network. Heparin and heparan sulfate bind to most Leishmania strains tested, and 6-O-sulfate groups play a crucial role in these interactions. Numerous Leishmania strains bind to tropoelastin, and some strains are even able to degrade it. Several strains interact with collagen VI, which is expressed by macrophages. Most Leishmania promastigotes interact with several regulators of angiogenesis, including antiangiogenic factors (endostatin, anastellin) and proangiogenic factors (ECM-1, VEGF, and TEM8 [also known as anthrax toxin receptor 1]), which are regulated by hypoxia. Since hypoxia modulates the infection of macrophages by the parasites, these interactions might influence the infection of host cells by Leishmania.

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Section: Resultsmentioning

confidence: 75%

Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging

et al. 2014

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“…Leishmania mexicana, one of the causative agents of cutaneous leishmaniasis on the American continent, has been reported to interact in vitro with plasminogen (Avilán et al 2000;Calcagno et al 2002). This interaction contributes to the virulence of the parasite as may be concluded from differences observed in lesion size and in the immunoreactivity pattern with anti-Leishmania antibodies in the lesion between plasminogen-deficient and wild-type mice (Maldonado et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Enolase as a plasminogen binding protein in Leishmania mexicana

et al. 2007

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Enolase is a glycolytic and gluconeogenic enzyme also found on the surface of several eukaryotic and prokaryotic cells where it acts as plasminogen binding protein. Leishmania mexicana, one of the causative agents of Leishmaniasis, binds plasminogen and, in this parasite, enolase has been previously found associated with the external face of the plasma membrane. In this work, we show that the purified recombinant enolase has plasminogen binding activity indicating that, at the surface of the parasite, the protein may function as one of the plasminogen receptors. An internal motif (249)AYDAERKMY(257), similar to the nine amino-acid internal plasminogen-binding motif in Streptococcus pneumoniae enolase, is responsible for plasminogen interaction with the parasite enolase. Anti-enolase antibodies inhibited up to 60% of plasminogen binding on live parasites indicating that enolase act as a plasminogen receptor on the parasite. The fact that enolase acts as a possible plasminogen receptor in vivo makes this protein a promising target for therapy.

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“…Enolase is present on the cell surface of several parasites, including Leishmania, where it has been shown to bind host plasminogen (14). It may therefore have a role in macrophage entry via plasminogen receptors and parasite dissemination from the sand fly bite site (15,16).…”

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confidence: 99%

The Oligopeptidase B of Leishmania Regulates Parasite Enolase and Immune Evasion

Swenerton¹,

Zhang²,

Sajid

et al. 2011

Journal of Biological Chemistry

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Proteases are a ubiquitous group of enzymes that play key roles in the life cycle of parasites, in the host-parasite relationship, and in the pathogenesis of parasitic diseases. Furthermore, proteases are targets for the development of new antiparasitic therapy. Protozoan parasites like Leishmania predominantly express Clan CA cysteine proteases for key life cycle functions. It was therefore unexpected to find a high level of serine protease activity expressed by Leishmania donovani. Purification of this activity followed by mass spectrometry identified oligopeptidase B (OPB; Clan SC, family S9A) as the responsible enzyme. This was confirmed by gene knock-out of OPB, which resulted in the disappearance of the detected serine protease activity of Leishmania extracts. To delineate the specific role of OPB in parasite physiology, proteomic analysis was carried out on OPB(؊/؊) versus wild type parasites. Four protein species were significantly elevated in OPB(؊/؊) parasites, and all four were identified by mass spectrometry as enolase. This increased enolase was enzymatically inactive and associated with the parasite membrane. Aside from its classic role in carbohydrate metabolism, enolase was recently found to localize to membranes, where it binds host plasminogen and functions as a virulence factor for several pathogens. As expected, there was a striking alteration in macrophage responses to Leishmania when OPB was deleted. Whereas wild type parasites elicited little, if any, response from infected macrophages, OPB(؊/؊) parasites induced a massive up-regulation in gene transcription. Additionally, these OPB(؊/؊) parasites displayed decreased virulence in the murine footpad infection model.Proteases are a ubiquitous group of enzymes functioning in nearly all biological phenomena. In protozoan parasites, proteases play key roles in life cycle transition, host invasion, parasite immune evasion, and the pathogenesis of parasitic diseases (1, 2). At least 50 cysteine proteases and twenty serine proteases are known to exist in the Leishmania genome (3-5).The molecular evolution of proteases shows a striking dichotomy between the predominant Clan CA cysteine proteases of protozoa and primitive metazoa and the dominant trypsin family (S1A) serine proteases of vertebrates (6). It was therefore unexpected to find that Leishmania donovani, Leishmania major, and Leishmania mexicana (but not the related kinetoplastid parasite, Trypanosoma cruzi) express high levels of serine protease activity, relative to cysteine protease activity in parasite extracts.To delineate the character of this serine protease activity, it was purified from Leishmania extracts and identified as Clan SC, family S9A oligopeptidase B by mass spectrometry. Oligopeptidase B (OPB) 2 has been identified in other protozoa, including T. cruzi, Trypanosoma brucei, and Trypanosoma evansi (7-9). These enzymes represent a subfamily of potential chemotherapeutic targets (10) because their inhibitors have been shown to be trypanocidal (4,11,12). OPB of T. cruzi is i...

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Interaction of Leishmania mexicana promastigotes with the plasminogen–plasmin system

Cited by 34 publications

References 36 publications

Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging

Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging

Enolase as a plasminogen binding protein in Leishmania mexicana

The Oligopeptidase B of Leishmania Regulates Parasite Enolase and Immune Evasion

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