Tilly Kit, Bestor Aaron, Rosa Patricia A
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana, USA
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana, USA.
Infect Immun. 2016 Apr 22;84(5):1565-1573. doi: 10.1128/IAI.00063-16. Print 2016 May.
Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse-tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization.
莱姆病病原体伯氏疏螺旋体在其鼠 - 蜱感染周期的不同阶段会产生不同的主要外表面脂蛋白。外表面蛋白A(OspA)从螺旋体进入蜱虫开始直到它们传播给哺乳动物的这段时间内覆盖着螺旋体。OspA是蜱虫正常定殖所必需的,并且已被证明能结合蜱虫中肠蛋白,这表明OspA可能作为蜱虫中肠黏附素。当感染性血餐来自不产生抗体的小鼠时,缺乏OspA的螺旋体在蜱虫中的定殖会增加,这表明OspA可能保护螺旋体免受宿主抗体的影响,因为宿主抗体不会识别诸如OspA等蜱虫特异性蛋白。为了进一步研究OspA在蜱虫定殖过程中的重要性,我们构建了一种伯氏疏螺旋体形式,其中位于lp54上的ospA开放阅读框分别被编码哺乳动物特异性或蜱虫特异性脂蛋白的ospC基因或ospB基因所取代。这些融合产生了一种在蜱虫体内(来自融合基因)以及早期哺乳动物感染期间(来自正常ospC基因座)产生OspC的菌株,以及一种在蜱虫体内产生OspB以替代OspA的菌株。在此我们表明,相关的蜱虫特异性蛋白OspB可以完全替代OspA,而不相关的哺乳动物特异性蛋白OspC则不能。这些数据来自三种不同的感染蜱虫的方法,它们证实并扩展了先前的研究,表明OspA既能保护蜱虫体内的螺旋体免受哺乳动物抗体的影响,又在蜱虫定殖过程中发挥额外作用。