Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response

Haile, Woldeab B.; Coleman, James L.; Benach, Jorge L.

doi:10.1111/j.1462-5822.2006.00717.x

Cited by 31 publications

(29 citation statements)

References 76 publications

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“…In this phase of the association, uPA fixed to the surface of inflammatory cells can activate the PLG bound to the Borrelia, with the possible result of enhancing dissemination of the spirochetes. Additional interactions include those involving PLG activation inhibitors (39) and metalloproteases (34,35,43). Few bacteria have such a complete association with a mammalian system.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, these spirochetes can fix plasmin onto their OMs, but they can also stimulate cells of the innate immune response to produce PLG activators (19,20,32,42,46) and modulate PLG activation inhibitors (39). In a similar manner, borreliae are important stimulators for the production of matrix metalloproteinases as part of their proinflammatory repertoire (34,35,43).…”

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confidence: 95%

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The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

et al. 2012

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The agent of Lyme disease, Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles of B. burgdorferi contain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination.

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Section: Discussionmentioning

confidence: 99%

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confidence: 95%

The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

et al. 2012

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“…We found that BAT2 supernatants from cells dually treated with BRSV and H. somni CCS showed an increased level of collagen IV degradation compared to those from BAT2 cells treated with either CCS or BRSV alone, consistent with MMP3 mRNA and protein levels. The basement membrane is a barrier against pathogen invasion (23,24), so degradation of the basement membrane proteins would allow H. somni to cross the inner alveolar barrier. Since H. somni causes septicemia in the natural host, crossing of the alveolar barrier to invade the bloodstream is critical to pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

et al. 2013

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cOur previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSVplus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection. R espiratory infections are characteristically polymicrobial. We previously investigated the mechanisms of viral and bacterial synergy in bovine respiratory disease (BRD) (1) by infecting calves with bovine respiratory syncytial virus (BRSV) followed by infection with Histophilus somni or with either pathogen alone. The calves dually infected with BRSV and H. somni had the most severe disease and the highest serum IgE antibody responses to H. somni (1). Duration of pneumonia and persistence of H. somni in the lungs were also greatest in dually infected animals (1). Our earlier immunohistochemistry studies of experimental H. somni pneumonia showed that the bacteria are detected primarily in the alveoli at 24 h after intrabronchial inoculation (2). Since H. somni causes septicemia and its sequelae (3), it is likely that it crosses into the circulation over the alveolar barrier. We also showed that the toxic Fic (filamentation induced by cyclic AMP [cAMP]) motifs of the direct repeat domains (DR1 and DR2) of the immunoglobulin binding protein A (IbpA) cause bovine alveolar type 2 (BAT2) cells to retract in vitro, allowing paracellular migration (4). This cytotoxicity is due to adenylylation of host cell Rho GTPases by the Fic motif (5). Conservation of IbpA and Fic motifs in all tested H. somni disease isolates was c...

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“…and Treponema denticola with possible implications for pathogenesis. 41,[49][50][51][52] PLA is a serine protease that can degrade a large spectrum of substrates, including fibrin clots, connective tissue, and components of extracellular matrices. 53,54 Human PLG/PLA proteolytic activity was first described for Leptospira spp.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Three Novel Adhesins of Leptospira interrogans

Siqueira¹,

Atzingen²,

Alves³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.

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Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response

Cited by 31 publications

References 76 publications

The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

Characterization of Three Novel Adhesins of Leptospira interrogans

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