Lyme disease spirochaetes possess an aggrecan-binding protease with aggrecanase activity

Mol Microbiol. 2013 Oct;90(2):228-40. doi: 10.1111/mmi.12276. Epub 2013 Jun 10.

Abstract

Connective tissues are the most common area of colonization for the Lyme disease spirochaete Borrelia burgdorferi. Colonization is aided by the interaction between numerous bacterial adhesins with components of the extracellular matrix (ECM). Here we describe a novel interaction between B. burgdorferi and the major ECM proteoglycan found in joints, aggrecan. Using affinity chromatography and mass spectrometry we identify two borrelial aggrecan-binding proteins: the known ECM ligand Bgp (BB0588) and an uncharacterized protease BbHtrA (BB0104). Proteinase K studies demonstrate that BbHtrA is surface exposed. Immunoblots using sera from patients with both early and late Lyme disease establish that BbHtrA is expressed during human disease, immunogenic, and conserved in the three major Lyme disease spirochaete species. Consequences of the interaction between aggrecan and BbHtrA were examined by proteolysis assays. BbHtrA cleaves aggrecan at a site known to destroy aggrecan function and which has been previously observed in the synovial fluid of patients with Lyme arthritis. These data demonstrate that B. burgdorferi possess aggrecan-binding proteins which may provide the organism with additional capability to colonize connective tissues. Moreover, our studies provide the first evidence that B. burgdorferi possess proteolytic activity which may contribute to the pathogenesis of Lyme arthritis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggrecans / metabolism*
  • Amino Acid Sequence
  • Bacterial Proteins / analysis
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Borrelia burgdorferi / genetics
  • Borrelia burgdorferi / metabolism*
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chromatography
  • Connective Tissue / metabolism
  • Connective Tissue / microbiology
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Evolution, Molecular
  • Extracellular Matrix / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Lyme Disease / metabolism
  • Lyme Disease / microbiology*
  • Mass Spectrometry
  • Molecular Sequence Data
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Serine Proteases / chemistry
  • Serine Proteases / genetics
  • Serine Proteases / metabolism
  • Synovial Fluid / metabolism
  • Synovial Fluid / microbiology

Substances

  • Aggrecans
  • Bacterial Proteins
  • Bgp protein, Borrelia burgdorferi
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Recombinant Proteins
  • Endopeptidases
  • Serine Proteases
  • aggrecanase