Characteristics of plasminogen binding to Trypanosoma cruzi epimastigotes

Rojas, Masyelly; Labrador, Indira; Concepción, Juan Luís; Aldana, Elis; Avilán, Luisana

doi:10.1016/j.actatropica.2008.04.013

Cited by 23 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several invasive gram-positive and gram-negative bacteria have been shown to interact with the host PLG system [20], [49], [50], [51], [52], a phenomenon that has also been observed with viruses [53], [54], [55] and parasites [56], either by expression of PLG receptors or stimulation of host activators. In the case of spirochetes, the plasminogen activation system was studied with several species of Borrelia with Treponema denticola and suggested to have an important role during infection [22], [23], [24], [25], [26].…”

Section: Discussionmentioning

confidence: 94%

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

et al. 2010

View full text Add to dashboard Cite

BackgroundLeptospirosis is a multisystem disease caused by pathogenic strains of the genus Leptospira. We have reported that Leptospira are able to bind plasminogen (PLG), to generate active plasmin in the presence of activator, and to degrade purified extracellular matrix fibronectin.Methodology/Principal FindingsWe have now cloned, expressed and purified 14 leptospiral recombinant proteins. The proteins were confirmed to be surface exposed by immunofluorescence microscopy and were evaluated for their ability to bind plasminogen (PLG). We identified eight as PLG-binding proteins, including the major outer membrane protein LipL32, the previously published rLIC12730, rLIC10494, Lp29, Lp49, LipL40 and MPL36, and one novel leptospiral protein, rLIC12238. Bound PLG could be converted to plasmin by the addition of urokinase-type PLG activator (uPA), showing specific proteolytic activity, as assessed by its reaction with the chromogenic plasmin substrate, D-Val-Leu-Lys 4-nitroanilide dihydrochloride. The addition of the lysine analog 6-aminocaproic acid (ACA) inhibited the protein-PLG interaction, thus strongly suggesting the involvement of lysine residues in plasminogen binding. The binding of leptospiral surface proteins to PLG was specific, dose-dependent and saturable. PLG and collagen type IV competed with LipL32 protein for the same binding site, whereas separate binding sites were observed for plasma fibronectin.Conclusions/SignificancePLG-binding/activation through the proteins/receptors on the surface of Leptospira could help the bacteria to specifically overcome tissue barriers, facilitating its spread throughout the host.

show abstract

Section: Discussionmentioning

confidence: 94%

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Several invasive bacterial pathogens utilize the PLG system to invade tissues [16], [35], [36], and use of this system has been extended to viruses [37] and parasites [38]. Increasing evidence proposes a so-called “bacterial metastasis” that is facilitated by the binding and activation of PLG and by the colonization and invasion of PLG-bound bacteria into tissues [35].…”

Section: Discussionmentioning

confidence: 99%

Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-Dependent Innate Immunity

et al. 2011

View full text Add to dashboard Cite

The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified α-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen.

show abstract

“…The process for binding to bacterial receptors on the cell surface has been shown for several pathogens to be mediated by the PLG kringle domains through the contained lysinebinding sites (2,10,16,32,33,46,63,68,77,78). Likewise, Leptospira probably interacts with PLG through the lysine residues because the binding and generation of active plasmin on the bacterial surface were inhibited by the presence of the lysine analogue ACA in the reaction.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that several pathogens, including the spirochete Borrelia burgdorferi, bind PLG on the surface and convert it to plasmin by host activators (6,13,16,19,22,31,34,37,38,60,68,73); this binding promotes degradation of ECM components and is essential for dissemination of the bacteria through the host tissues, suggesting its role during infection and pathogenesis (12,14,15,28,37,58).…”

mentioning

confidence: 99%

Plasminogen Acquisition and Activation at the Surface of Leptospira Species Lead to Fibronectin Degradation

et al. 2009

View full text Add to dashboard Cite

Pathogenic Leptospira species are the etiological agents of leptospirosis, a widespread disease of human and veterinary concern. In this study, we report that Leptospira species are capable of binding plasminogen (PLG) in vitro. The binding to the leptospiral surface was demonstrated by indirect immunofluorescence confocal microscopy with living bacteria. The PLG binding to the bacteria seems to occur via lysine residues because the ligation is inhibited by addition of the lysine analog 6-aminocaproic acid. Exogenously provided urokinase-type PLG activator (uPA) converts surface-bound PLG into enzymatically active plasmin, as evaluated by the reaction with the chromogenic plasmin substrate D-Val-Leu-Lys 4-nitroanilide dihydrochloridein. The PLG activation system on the surface of Leptospira is PLG dose dependent and does not cause injury to the organism, as cellular growth in culture was not impaired. The generation of active plasmin within Leptospira was observed with several nonvirulent high-passage strains and with the nonpathogenic saprophytic organism Leptospira biflexa. Statistically significant higher activation of plasmin was detected with a low-passage infectious strain of Leptospira. Plasmin-coated virulent Leptospira interrogans bacteria were capable of degrading purified extracellular matrix fibronectin. The breakdown of fibronectin was not observed with untreated bacteria. Our data provide for the first time in vitro evidence for the generation of active plasmin on the surface of Leptospira, a step that may contribute to leptospiral invasiveness.

show abstract

Characteristics of plasminogen binding to Trypanosoma cruzi epimastigotes

Cited by 23 publications

References 23 publications

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-Dependent Innate Immunity

Plasminogen Acquisition and Activation at the Surface of Leptospira Species Lead to Fibronectin Degradation

Contact Info

Product

Resources

About