Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C. PLoS Pathog 2020 May;16(5):e1008516
Date
05/16/2020Pubmed ID
32413091Pubmed Central ID
PMC7255614DOI
10.1371/journal.ppat.1008516Scopus ID
2-s2.0-85085664567 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Lyme disease, caused by Borrelia burgdorferi, B. afzelii and B. garinii, is a chronic, multi-systemic infection and the spectrum of tissues affected can vary with the Lyme disease strain. For example, whereas B. garinii infection is associated with neurologic manifestations, B. burgdorferi infection is associated with arthritis. The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components fibronectin and/or dermatan sulfate in an OspC variant-dependent manner. Murine infection by isogenic B. burgdorferi strains differing only in their ospC coding region revealed that two OspC variants capable of binding dermatan sulfate promoted colonization of all tissues tested, including joints. However, an isogenic strain producing OspC from B. garinii strain PBr, which binds fibronectin but not dermatan sulfate, colonized the skin, heart and bladder, but not joints. Moreover, a strain producing an OspC altered to recognize neither fibronectin nor dermatan sulfate displayed dramatically reduced levels of tissue colonization that were indistinguishable from a strain entirely deficient in OspC. Finally, intravital microscopy revealed that this OspC mutant, in contrast to a strain producing wild type OspC, was defective in promoting joint invasion by B. burgdorferi in living mice. We conclude that OspC functions as an ECM-binding adhesin that is required for joint invasion, and that variation in OspC sequence contributes to strain-specific differences in tissue tropism displayed among Lyme disease spirochetes.
Author List
Lin YP, Tan X, Caine JA, Castellanos M, Chaconas G, Coburn J, Leong JMAuthor
Jenifer Coburn PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Bacterial
Bacterial Adhesion
Bacterial Outer Membrane Proteins
Borrelia burgdorferi
Dermatan Sulfate
Extracellular Matrix
Female
Fibronectins
Joint Diseases
Joints
Lyme Disease
Mice
Mice, SCID
Mutation
Organ Specificity
