Borrelia burgdorferi lacking BBK32, a fibronectin-binding protein, retains full pathogenicity

Borrelia burgdorferi lacking BBK32, a fibronectin-binding protein, retains full pathogenicity
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DOI:
10.1128/iai.02035-05
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发表时间:
2006-06-01
影响因子:
3.1
通讯作者:
Fikrig, Erol
Fikrig, Erol
中科院分区:
医学2区
文献类型:
--
作者:
Li, Xin;Liu, Xianzhong;Fikrig, Erol

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BBK32是伯氏疏螺旋体的一种纤维连接蛋白结合蛋白,是莱姆病螺旋体在其生命周期的不同阶段差异表达的众多表面脂蛋白之一。BBK32在伯氏疏螺旋体中的表达水平在哺乳动物宿主感染期间最高,在扁蜱中最低。这种时间表达谱及其纤维连接蛋白结合活性强烈表明,BBK32可能在宿主莱姆病发病中发挥重要作用。为了验证这一假设,我们通过同源重组将野生型伯氏疏螺旋体B31中的BBK32基因替换为卡那霉素抗性盒,构建了一个等基因缺失突变体。我们在伯氏疏螺旋体生命周期的实验小鼠-蜱模型中广泛检测了野生型菌株和BBK32缺失突变体。我们的数据表明,缺乏BBK32的伯氏疏螺旋体在小鼠体内保持完全的致病性,无论小鼠是通过注射器接种人工感染还是通过蜱叮咬自然感染。突变体中BBK32表达的缺失对螺旋体获得(小鼠到蜱)和传播(蜱到小鼠)过程没有不利影响。这些结果表明,在天然螺旋体生命周期中,额外的伯氏疏螺旋体蛋白可以补充BBK32的功能,结合纤维连接蛋白或其他功能。
BBK32, a fibronectin-binding protein of Borrelia burgdorferi, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in B. burgdorferi is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type B. burgdorferi B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the Borrelia life cycle. Our data indicated that B. burgdorferi lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.