Shi Yanlin, Xu Qilong, Seemanaplli Sunita V, McShan Kristy, Liang Fang Ting
Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
PLoS One. 2008 Oct 3;3(10):e3340. doi: 10.1371/journal.pone.0003340.
As an extracellular bacterium, the Lyme disease spirochete Borrelia burgdorferi resides primarily in the extracellular matrix and connective tissues and between host cells during mammalian infection, where decorin and glycosaminoglycans are abundantly found, so its interactions with these host ligands potentially affect various aspects of infection. Decorin-binding proteins (Dbps) A and B, encoded by a 2-gene operon, are outer surface lipoproteins with similar molecular weights and share approximately 40% identity, and both bind decorin and glycosaminoglycans. To investigate how DbpA and DbpB contribute differently to the overall virulence of B. burgdorferi, a dbpAB mutant was modified to overproduce the adhesins. Overproduction of either DbpA or DbpB resulted in restoration of the infectivity of the mutant to the control level, measured by 50% infectious dose (ID(50)), indicating that the two virulence factors are interchangeable in this regard. Overproduction of DbpA also allowed the mutant to disseminate to some but not all distal tissues slightly slower than the control, but the mutant with DbpB overproduction showed severely impaired dissemination to all tissues that were analyzed. The mutant with DbpA overproduction colonized all tissues, albeit generating bacterial loads significantly lower than the control in heart and joint, while the mutant overproducing DbpB remained severely defective in heart colonization and registered bacterial loads substantially lower than the control in joint. Taken together, the study indicated that DbpA and DbpB play a similar role in contribution to infectivity as measured by ID(50) value but contribute differently to dissemination and tissue colonization.
作为一种胞外细菌，莱姆病螺旋体伯氏疏螺旋体在哺乳动物感染期间主要存在于细胞外基质、结缔组织以及宿主细胞之间，在这些部位可大量发现核心蛋白聚糖和糖胺聚糖，因此其与这些宿主配体的相互作用可能会影响感染的各个方面。由一个双基因操纵子编码的核心蛋白聚糖结合蛋白（Dbps）A和B是分子量相似的外表面脂蛋白，它们的序列相似度约为40%，且都能结合核心蛋白聚糖和糖胺聚糖。为了研究DbpA和DbpB对伯氏疏螺旋体整体毒力的贡献有何不同，对一个dbpAB突变体进行改造，使其过量表达黏附素。通过50%感染剂量（ID50）测定，过量表达DbpA或DbpB均可使突变体的感染性恢复到对照水平，这表明在这方面这两种毒力因子是可互换的。过量表达DbpA还使突变体扩散到部分但并非所有远端组织的速度略慢于对照，但过量表达DbpB的突变体在所有分析的组织中扩散均严重受损。过量表达DbpA的突变体可在所有组织中定殖，尽管其在心脏和关节中的细菌载量显著低于对照，而过量表达DbpB的突变体在心脏定殖方面仍存在严重缺陷，并且在关节中的细菌载量远低于对照。综上所述，该研究表明，以ID50值衡量，DbpA和DbpB在对感染性的贡献方面发挥相似作用，但在扩散和组织定殖方面贡献不同。
