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Decorin binding proteins of Borrelia burgdorferi promote arthritis development and joint specific post-treatment DNA persistence in mice.

Abstract
Decorin binding proteins A and B (DbpA and B) of Borrelia burgdorferi are of critical importance for the virulence of the spirochete. The objective of the present study was to further clarify the contribution of DbpA and B to development of arthritis and persistence of B. burgdorferi after antibiotic treatment in a murine model of Lyme borreliosis. With that goal, mice were infected with B. burgdorferi strains expressing either DbpA or DbpB, or both DbpA and B, or with a strain lacking the adhesins. Arthritis development was monitored up to 15 weeks after infection, and bacterial persistence was studied after ceftriaxone and immunosuppressive treatments. Mice infected with the B. burgdorferi strain expressing both DbpA and B developed an early and prominent joint swelling. In contrast, while strains that expressed DbpA or B alone, or the strain that was DbpA and B deficient, were able to colonize mouse joints, they caused only negligible joint manifestations. Ceftriaxone treatment at two or six weeks of infection totally abolished joint swelling, and all ceftriaxone treated mice were B. burgdorferi culture negative. Antibiotic treated mice, which were immunosuppressed by anti-TNF-alpha, remained culture negative. Importantly, among ceftriaxone treated mice, B. burgdorferi DNA was detected by PCR uniformly in joint samples of mice infected with DbpA and B expressing bacteria, while this was not observed in mice infected with the DbpA and B deficient strain. In conclusion, these results show that both DbpA and B adhesins are crucial for early and prominent arthritis development in mice. Also, post-treatment borrelial DNA persistence appears to be dependent on the expression of DbpA and B on B. burgdorferi surface. Results of the immunosuppression studies suggest that the persisting material in the joints of antibiotic treated mice is DNA or DNA containing remnants rather than live bacteria.
AuthorsJemiina Salo, Annukka Jaatinen, Mirva Söderström, Matti K Viljanen, Jukka Hytönen
JournalPloS one (PLoS One) Vol. 10 Issue 3 Pg. e0121512 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID25816291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adhesins, Bacterial
  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DdpB protein, Borrelia burgdorferi
  • Immunosuppressive Agents
  • Ceftriaxone
Topics
  • Adhesins, Bacterial (genetics, metabolism)
  • Animals
  • Anti-Bacterial Agents (administration & dosage, pharmacology)
  • Borrelia burgdorferi (drug effects, genetics, metabolism)
  • Ceftriaxone (administration & dosage, pharmacology)
  • DNA, Bacterial (analysis, drug effects)
  • Disease Models, Animal
  • Immunosuppressive Agents (administration & dosage, pharmacology)
  • Lyme Disease (drug therapy, microbiology, pathology)
  • Mice
  • Treatment Outcome

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