title: The early dissemination defect attributed to disruption of decorin-binding proteins is abolished in chronic murine Lyme borreliosis.
abstract: The laboratory mouse model of Lyme disease has revealed that Borrelia burgdorferi differentially expresses numerous outer surface proteins that influence different stages of infection (tick-borne transmission, tissue colonization, dissemination, persistence, and tick acquisition). Deletion of two such outer surface proteins, decorin-binding proteins A and B (DbpA/B), has been documented to decrease infectivity, impede early dissemination, and, possibly, prevent persistence. In this study, DbpA/B-deficient spirochetes were confirmed to exhibit an early dissemination defect in immunocompetent, but not immunodeficient, mice, and the defect was found to resolve with chronicity. Development of disease (arthritis and carditis) was attenuated only in the early stage of infection with DbpA/B-deficient spirochetes in both types of mice. Persistence of the DbpA/B-deficient spirochetes occurred in both immunocompetent and immunodeficient mice in a manner indistinguishable from that of wild-type spirochetes. Dissemination through the lymphatic system was evaluated as an underlying mechanism for the early dissemination defect. At 12 h, 3 days, 7 days, and 14 days postinoculation, DbpA/B-deficient spirochetes were significantly less prevalent and in lower numbers in lymph nodes than wild-type spirochetes. However, in immunodeficient mice, deficiency of DbpA/B did not significantly decrease the prevalence or spirochete numbers in lymph nodes. Complementation of DbpA/B restored a wild-type phenotype. Thus, the results indicated that deficiency of DbpA/B allows the acquired immune response to restrict early dissemination of spirochetes, which appears to be at least partially mediated through the lymphatic system.
authors: Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California at Davis, Davis, California, USA.
authors: Denise M
authors: DM
authors: Imai
authors: D Scott
authors: DS
authors: Samuels
authors: Sunlian
authors: S
authors: Feng
authors: Emir
authors: E
authors: Hodzic
authors: Kim
authors: K
authors: Olsen
authors: Stephen W
authors: SW
authors: Barthold
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D025065:Borrelia burgdorferi / Q000472:pathogenicity*; D002908:Chronic Disease; D005260:Female; D016867:Immunocompromised Host; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology*; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID
chemical_list: D018829:Adhesins, Bacterial; C112557:DdpB protein, Borrelia burgdorferi