Increasing the interaction of Borrelia burgdorferi with decorin significantly reduces the 50 percent infectious dose and severely impairs dissemination.
Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of decorin-binding protein A (DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID(50)), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing DbpA expression dramatically increased the interaction of B. burgdorferi with decorin and sensitivity to growth inhibition/killing by anti-DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of decorin. Increasing DbpA expression significantly reduced ID(50) values and severely impaired dissemination in severe combined immunodeficiency (SCID) and immunocompetent mice. During infection of SCID mice, B. burgdorferi with increased DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating arthritis virulence. Although increasing DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian infection.
Xu
Qilong
Q
Department of Pathobiological Sciences, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA 70803, USA.
Seemanaplli
Sunita V
SV
McShan
Kristy
K
Liang
Fang Ting
FT
D018829:Adhesins, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001899:Borrelia Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D025065:Borrelia burgdorferi / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D011509:Proteoglycans / Q000502:physiology*
D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; C546879:Dcn protein, mouse; C112557:DdpB protein, Borrelia burgdorferi; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans