Article

The enolase of Borrelia burgdorferi is a plasminogen receptor released in outer membrane vesicles.

Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
Infection and immunity (Impact Factor: 4.16). 11/2011; 80(1):359-68. DOI: 10.1128/IAI.05836-11
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Alvaro Toledo, Jul 30, 2015
1 Follower
 · 
166 Views
  • Source
    • "In contrast, a third group found BB0337 in outer membrane vesicles, but did not detect enolase on the outer surface of B. burgdorferi by proteinase K digestion or by electron microscopy (Toledo et al., 2012). In addition, Toledo et al. demonstrated that enolase was recognized by host antibodies from tick-infected mice, rabbits, and human Lyme disease patients (Toledo et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adhesion is the initial event in the establishment of any infection. Borrelia burgdorferi, the etiological agent of Lyme disease, possesses myriad proteins termed adhesins that facilitate contact with its vertebrate hosts. B. burgdorferi adheres to host tissues through interactions with host cells and extracellular matrix, as well as other molecules present in serum and extracellular fluids. These interactions, both general and specific, are critical in the establishment of infection. Modulation of borrelial adhesion to host tissues affects the microorganisms's ability to colonize, disseminate, and persist. In this review, we update the current knowledge on structure, function, and role in pathogenesis of these "sticky" B. burgdorferi infection-associated proteins.
    Frontiers in Cellular and Infection Microbiology 04/2014; 4:41. DOI:10.3389/fcimb.2014.00041 · 2.62 Impact Factor
  • Source
    • "After transport from the cytosol across the inner membrane via the Sec translocation pathway, they are released into the periplasm upon signal peptide cleavage, where they function in their characteristic roles (Lipinska et al., 1990; Waller and Sauer, 1996; Dalbey et al., 2012). HtrABb first drew our interest when it was found to be a constituent of B. burgdorferi vesicles (Toledo et al., 2012). Many Gram-negative bacteria release vesicles, which contain both outer membrane and periplasmic elements, as part of the bacterial stress response (McBroom and Kuehn, 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Borrelia burgdorferi, the spirochaetal agent of Lyme disease, codes for a single HtrA protein, HtrABb (BB0104) that is homologous to DegP of Escherichia coli (41% amino acid identity). HtrABb shows physical and biochemical similarities to DegP in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. Recombinant HtrABb exhibits proteolytic activity in vitro, while a mutant (HtrABbS198A) does not. However, HtrABb and DegP have some important differences as well. Native HtrABb occurs in both membrane-bound and soluble forms. Despite its homology to DegP, HtrABb could not complement an E. coli DegP deletion mutant. Late stage Lyme disease patients, as well as infected mice and rabbits developed a robust antibody response to HtrABb, indicating that it is a B-cell antigen. In co-immunoprecipitation studies, a number of potential binding partners for HtrABb were identified, as well as two specific proteolytic substrates, basic membrane protein D (BmpD/BB0385) and chemotaxis signal transduction phosphatase CheX (BB0671). HtrABb may function in regulating outer membrane lipoproteins and in modulating the chemotactic response of B. burgdorferi.
    Molecular Microbiology 04/2013; 88(3). DOI:10.1111/mmi.12213 · 5.03 Impact Factor
  • Source
    • "[15] [32] [33]. In addition, exosomes from Leishmania spp. as well other exosomes or outer membrane vesicles from other cells [15] [30] [34] [35] contain enolase, a plasminogen binding protein in many cells and microorganisms including L. mexicana [8]. Indeed, the secreted membrane vesicle preparations in this study contained this protein (Fig. 2C). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Membrane vesicles secreted by Leishmania mexicana were collected and analyzed. These vesicles can bind plasminogen and were shown to contain enolase, previously identified as a plasminogen-binding protein. In addition, another plasminogen-binding protein was identified, the small myristoylated protein, SMP-1. Recombinant SMP-1 was able to bind plasminogen in a lysine-dependent manner with a K(d) value of 0.24μM. The C-terminal lysine seems to be responsible for this binding, since this recognition decreases upon carboxypeptidase B treatment. This protein was present within the secreted membrane vesicles as demonstrated by its protection from trypsin digestion in the absence of Triton X-100. Plasminogen-binding proteins in the secreted vesicles may be involved in parasite invasion in the mammalian host.
    Molecular and Biochemical Parasitology 11/2012; 187(1). DOI:10.1016/j.molbiopara.2012.11.002 · 2.24 Impact Factor
Show more