OspC is potent plasminogen receptor on surface of Borrelia burgdorferi

J Biol Chem. 2012 May 11;287(20):16860-8. doi: 10.1074/jbc.M111.290775. Epub 2012 Mar 20.

Abstract

Host-derived proteases are crucial for the successful infection of vertebrates by several pathogens, including the Lyme disease spirochete bacterium, Borrelia burgdorferi. B. burgdorferi must traverse tissue barriers in the tick vector during transmission to the host and during dissemination within the host, and it must disrupt immune challenges to successfully complete its infectious cycle. It has been proposed that B. burgdorferi can accomplish these tasks without an endogenous extra-cytoplasmic protease by commandeering plasminogen, the highly abundant precursor of the vertebrate protease plasmin. However, the molecular mechanism by which B. burgdorferi immobilizes plasminogen to its surface remains obscure. The data presented here demonstrate that the outer surface protein C (OspC) of B. burgdorferi is a potent plasminogen receptor on the outer membrane of the bacterium. OspC-expressing spirochetes readily bind plasminogen, whereas only background levels of plasminogen are detectable on OspC-deficient strains. Furthermore, plasminogen binding by OspC-expressing spirochetes can be significantly reduced using anti-OspC antibodies. Co-immunofluorescence staining assays demonstrate that wild-type bacteria immobilize plasminogen only if they are actively expressing OspC regardless of the expression of other surface proteins. The co-localization of plasminogen and OspC on OspC-expressing spirochetes further implicates OspC as a biologically relevant plasminogen receptor on the surface of live B. burgdorferi.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Bacterial / biosynthesis*
  • Antigens, Bacterial / genetics
  • Bacterial Outer Membrane Proteins / agonists
  • Bacterial Outer Membrane Proteins / biosynthesis*
  • Bacterial Outer Membrane Proteins / genetics
  • Borrelia burgdorferi / genetics
  • Borrelia burgdorferi / metabolism*
  • Borrelia burgdorferi / pathogenicity
  • Gene Expression Regulation, Bacterial / physiology*
  • Humans
  • Lyme Disease / genetics
  • Lyme Disease / metabolism*
  • Plasminogen / genetics
  • Plasminogen / metabolism*

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • OspC protein
  • Plasminogen