Rogers Elizabeth A, Abdunnur Shane V, McDowell John V, Marconi Richard T
Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678, USA.
Infect Immun. 2009 Oct;77(10):4396-405. doi: 10.1128/IAI.00393-09. Epub 2009 Jul 20.
Borrelia burgdorferi CspZ (BBH06/BbCRASP-2) binds the complement regulatory protein factor H (FH) and additional unidentified serum proteins. The goals of this study were to assess the ligand binding capability of CspZ orthologs derived from an extensive panel of human Lyme disease isolates and to further define the molecular basis of the interaction between FH and CspZ. While most B. burgdorferi CspZ orthologs analyzed bound FH, specific, naturally occurring polymorphisms, most of which clustered in a specific loop domain of CspZ, prevented FH binding in some orthologs. Sequence analyses also revealed the existence of CspZ phyletic groups that correlate with FH binding and with the relationships inferred from ribosomal spacer types (RSTs). CspZ type 1 (RST1) and type 3 (RST3) strains bind FH, while CspZ type 2 (RST2) strains do not. Antibody responses to CspZ were also assessed. Anti-CspZ antibodies were detected in mice by week 2 of infection, indicating that there was expression during early-stage infection. Analyses of sera collected from infected mice suggested that CspZ production continued over the course of long-term infection as the antibody titer increased over time. While antibody to CspZ was detected in several human Lyme disease serum samples, the response was not universal, and the titers were generally low. Vaccination studies with mice demonstrated that while CspZ is immunogenic, it does not elicit an antibody that is protective or that inhibits dissemination. The data presented here provide significant new insight into the interaction between CspZ and FH and suggest that there is a correlation between CspZ production and dissemination. However, in spite of its possible contributory role in pathogenesis, the immunological analyses indicated that CspZ is likely to have limited potential as a diagnostic marker and vaccine candidate for Lyme disease.
伯氏疏螺旋体CspZ（BBH06/BbCRASP-2）可结合补体调节蛋白H因子（FH）及其他未鉴定的血清蛋白。本研究的目的是评估来自大量人类莱姆病分离株的CspZ直系同源物的配体结合能力，并进一步确定FH与CspZ之间相互作用的分子基础。虽然分析的大多数伯氏疏螺旋体CspZ直系同源物都能结合FH，但特定的自然发生的多态性（其中大多数聚集在CspZ的特定环结构域中）阻止了某些直系同源物与FH的结合。序列分析还揭示了CspZ系统发育组的存在，这些组与FH结合以及从核糖体间隔区类型（RST）推断的关系相关。CspZ 1型（RST1）和3型（RST3）菌株能结合FH，而CspZ 2型（RST2）菌株则不能。还评估了对CspZ的抗体反应。在感染第2周时在小鼠中检测到抗CspZ抗体，表明在早期感染期间有表达。对感染小鼠采集的血清分析表明，随着抗体滴度随时间增加，CspZ在长期感染过程中持续产生。虽然在几份人类莱姆病血清样本中检测到了抗CspZ抗体，但这种反应并不普遍，而且滴度通常较低。对小鼠的疫苗接种研究表明，虽然CspZ具有免疫原性，但它不会引发具有保护性或抑制传播作用的抗体。此处提供的数据为CspZ与FH之间的相互作用提供了重要的新见解，并表明CspZ产生与传播之间存在相关性。然而，尽管其在发病机制中可能起作用，但免疫学分析表明，CspZ作为莱姆病的诊断标志物和疫苗候选物的潜力可能有限。
