Abstract：
Lyme disease, the leading vector-borne disease in the United States and Europe, develops after infection with Borrelia burgdorferi sensu lato bacteria. Transmission of the spirochete from the tick vector to a vertebrate host requires global changes in gene expression that are controlled, in part, by the Rrp2/RpoN/RpoS alternative sigma factor cascade. Transcriptional studies defining the B. burgdorferi RpoS regulon have suggested that RpoS activates the transcription of paralogous family 52 (PFam52) genes. In strain B31, PFam52 genes (bbi42, bbk53, and bbq03) encode a set of conserved hypothetical proteins with >89% amino acid identity that are predicted to be surface-localized. Extensive homology among members of paralogous families complicates studies of protein contributions to pathogenicity as the potential for functional redundancy will obfuscate findings. Using a sequential mutagenesis approach, we generated clones expressing a single PFam52 paralog, as well as a strain deficient in all three. The single paralog expressing strains were used to confirm BBI42, BBK53, and BBQ03 surface localization and RpoS regulation. Surprisingly, the PFam52-deficient strain was able to infect mice and complete the enzootic cycle similar to the wild-type parental strain. Indeed, the presence of numerous pseudogenes that contain frameshifts or internal stop codons among the PFam52 genes suggests that they may be subjected to gene loss in B. burgdorferi\'s reduced genome. Alternatively, the lack of phenotype might reflect the limitations of the experimental mouse infection model.
摘要：
莱姆病,美国和欧洲主要的媒介传播疾病，感染伯氏疏螺旋体后发展。螺旋体从蜱载体到脊椎动物宿主的传播需要基因表达的整体变化，在某种程度上,通过Rrp2/RpoN/RpoS替代sigma因子级联。定义B.burgdorferiRpoS调节子的转录研究表明，RpoS激活了旁系家族52（PFam52）基因的转录。在菌株B31中，PFam52基因（bbi42，bbk53和bbq03）编码一组保守的假设蛋白质，其氨基酸同一性>89％，被预测为表面定位。旁系家族成员之间的广泛同源性使蛋白质对致病性的贡献研究变得复杂，因为功能冗余的潜力将混淆发现。使用顺序诱变方法，我们产生了表达单个PFam52旁系物的克隆，以及这三个菌株都缺乏。使用表达单个同源物的菌株来确认BBI42、BBK53和BBQ03表面定位和RpoS调节。令人惊讶的是,PFam52缺陷型菌株能够感染小鼠,并完成与野生型亲本菌株相似的植物学周期.的确,在PFam52基因中存在大量含有移码或内部终止密码子的假基因，这表明它们可能在伯氏芽孢杆菌减少的基因组中发生基因丢失。或者，缺乏表型可能反映了实验性小鼠感染模型的局限性。
