Salo Jemiina, Jaatinen Annukka, Söderström Mirva, Viljanen Matti K, Hytönen Jukka
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland; Turku Doctoral Programme of Biomedical Sciences, TuBS, Turku, Finland.
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland; Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku, Finland.
PLoS One. 2015 Mar 27;10(3):e0121512. doi: 10.1371/journal.pone.0121512. eCollection 2015.
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.
伯氏疏螺旋体的饰胶蛋白结合蛋白A和B（DbpA和B）对该螺旋体的毒力至关重要。本研究的目的是在莱姆病螺旋体病的小鼠模型中，进一步阐明DbpA和B在关节炎发展以及抗生素治疗后伯氏疏螺旋体持续存在方面所起的作用。为实现这一目标，用表达DbpA或DbpB、或同时表达DbpA和B的伯氏疏螺旋体菌株，或用缺乏黏附素的菌株感染小鼠。在感染后长达15周监测关节炎的发展情况，并在头孢曲松和免疫抑制治疗后研究细菌的持续存在情况。感染同时表达DbpA和B的伯氏疏螺旋体菌株的小鼠出现了早期且明显的关节肿胀。相比之下，虽然单独表达DbpA或B的菌株，或缺乏DbpA和B的菌株能够在小鼠关节中定植，但它们仅引起了可忽略不计的关节表现。在感染后两周或六周进行头孢曲松治疗完全消除了关节肿胀，并且所有接受头孢曲松治疗的小鼠伯氏疏螺旋体培养均为阴性。经抗TNF-α免疫抑制的抗生素治疗小鼠仍培养阴性。重要的是，在接受头孢曲松治疗的小鼠中，在用表达DbpA和B的细菌感染的小鼠关节样本中通过PCR均能检测到伯氏疏螺旋体DNA，而在感染缺乏DbpA和B菌株的小鼠中未观察到这种情况。总之，这些结果表明DbpA和B黏附素对于小鼠早期和明显的关节炎发展都至关重要。此外，治疗后螺旋体DNA的持续存在似乎取决于伯氏疏螺旋体表面DbpA和B的表达。免疫抑制研究结果表明，抗生素治疗小鼠关节中持续存在的物质是DNA或含有DNA的残余物，而非活细菌。
