title: Lyme disease spirochaetes possess an aggrecan-binding protease with aggrecanase activity.
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.
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Russell
authors.forename: Barbara J B
authors.initials: BJ
authors.lastname: Johnson
mesh_terms: D053674:Aggrecans / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002845:Chromatography; D003238:Connective Tissue / Q000378:metabolism / Q000382:microbiology; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008193:Lyme Disease / Q000378:metabolism / Q000382:microbiology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D057057:Serine Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism / Q000382:microbiology
chemical_list: D053674:Aggrecans; D001426:Bacterial Proteins; C474476:Bgp protein, Borrelia burgdorferi; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D011994:Recombinant Proteins; D010450:Endopeptidases; D057057:Serine Proteases; C083641:aggrecanase