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: 3.73). 11/2011; 80(1):359-68. DOI: 10.1128/IAI.05836-11
Source: PubMed


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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Available from: Alvaro Toledo
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    • "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). "
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    • "At 0.1 M, the protein is clearly saturated but the Str enolase/Pgn complex only partially dissociates. The results with 6-aminohexanoate are similar to those of found by others [44]–[46]. It is clear that binding of Pgn to the bilayer/Str enolase mixture involves groups other than just the two carboxy-terminal lysines "
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    • "Enolase has been shown to function as a Pg receptor on the cell surface of a variety of other pathogens [38,44,45,58-60]. The interactions of pathogenic spirochetes L. interrogans, B. burgdorferi, and T. denticola with Pg has been studied [35,38,47,49,50,61]; especially in the case of Lyme disease spirochetes, enolase-Pg interaction has been suggested to support B. burgdorferi survival in the vector [38]. However, potential contribution of enolase in L. interrogans-Pg interaction and in infectivity remains unexplored. "
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