Weening Eric H, Parveen Nikhat, Trzeciakowski Jerome P, Leong John M, Höök Magnus, Skare Jonathan T
Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA.
Infect Immun. 2008 Dec;76(12):5694-705. doi: 10.1128/IAI.00690-08. Epub 2008 Sep 22.
Several Borrelia burgdorferi genes induced under mammalian host conditions have been purported to be important in Lyme disease pathogenesis based on their binding to host structures. These genes include the dbpBA locus, whose products bind host decorin and glycosoaminoglycans. Recently, the dbpBA genes were reported to be involved in borrelial infectivity. Here we extended the previous observations by using culture and quantitative PCR to evaluate low- and high-dose murine infection by a Delta dbpBA::Gent(r) derivative of B. burgdorferi strain B31. The results indicate that the Delta dbpBA::Gent(r) mutant is attenuated in the ability to initially colonize and then persist in multiple tissues. The mutant exhibited a colonization defect as early as 3 days postinfection, before the development of an adaptive immune response, and after low-dose infection of SCID mice, which are deficient in adaptive immunity. These findings suggest that the inability to adhere to host decorin may promote clearance of B. burgdorferi, presumably via innate immune mechanisms. In a high-dose infection, the mutant disseminated to several tissues, particularly joint tissue, but it was generally cleared from these tissues by 3 weeks postinfection. Finally, following high-dose infection of SCID mice, the dbpBA mutant exhibited only a mild colonization defect, suggesting that the adaptive response is involved in the clearance of the mutant in immunocompetent mice. Taken together, these results suggest that the DbpBA proteins facilitate the colonization of multiple tissues by B. burgdorferi and are required for optimal resistance to both innate and adaptive immune mechanisms following needle inoculation.
一些在哺乳动物宿主条件下诱导表达的伯氏疏螺旋体基因，因其与宿主结构的结合作用，被认为在莱姆病发病机制中具有重要意义。这些基因包括dbpBA位点，其产物可结合宿主的核心蛋白聚糖和糖胺聚糖。最近，有报道称dbpBA基因与疏螺旋体的感染性有关。在此，我们通过培养和定量PCR扩展了先前的观察结果，以评估伯氏疏螺旋体B31菌株的ΔdbpBA::Gent(r)衍生物对小鼠的低剂量和高剂量感染情况。结果表明，ΔdbpBA::Gent(r)突变体在最初定殖以及随后在多个组织中持续存在的能力上有所减弱。早在感染后3天，在适应性免疫反应出现之前，以及在缺乏适应性免疫的SCID小鼠低剂量感染后，该突变体就表现出定殖缺陷。这些发现表明，无法黏附宿主核心蛋白聚糖可能会促进伯氏疏螺旋体的清除，推测是通过先天免疫机制实现的。在高剂量感染中，该突变体扩散到多个组织，尤其是关节组织，但在感染后3周时通常会从这些组织中清除。最后，在对SCID小鼠进行高剂量感染后，dbpBA突变体仅表现出轻微的定殖缺陷，这表明适应性反应参与了免疫健全小鼠中该突变体的清除过程。综上所述，这些结果表明DbpBA蛋白促进了伯氏疏螺旋体在多个组织中的定殖，并且是针接种后对先天和适应性免疫机制产生最佳抗性所必需的。
