Two regulatory elements required for enhancing ospA expression in Borrelia burgdorferi grown in vitro but repressing its expression during mammalian infection.

Two regulatory elements required for enhancing ospA expression in Borrelia burgdorferi grown in vitro but repressing its expression during mammalian infection.
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DOI:
10.1099/mic.0.036608-0
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发表时间:
2010-07
期刊:
Microbiology (Reading, England)
影响因子:
--
通讯作者:
Liang FT
Liang FT
中科院分区:
其他
文献类型:
--
作者:
Xu Q;McShan K;Liang FT

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在蜱虫载体和哺乳动物之间的循环过程中,莱姆病螺旋体伯氏疏螺旋体必须协调外表面蛋白(Osps)A和B的表达,以快速响应环境变化。病原体在蜱中大量产生OspA/B,但在哺乳动物感染期间抑制它们的表达。本文报道了一个调控结构,由两个序列侧翼的ospAB启动子,这是增强ospA在B中的表达所需的。burgdorferi在体外生长,但在小鼠感染期间抑制其表达。缺失或替换ospAB启动子的上游或下游序列导致ospA表达在体外显著降低,但在小鼠感染期间显著增加。任一序列与flaB报告基因启动子的融合导致ospA报告基因在体外的表达增加,但在小鼠宿主中的表达减少。此外,同时融合的两个序列与报告启动子显示出协同效应,在体外增强ospA报告的表达,但抑制其在小鼠感染过程中的表达。总之,结果表明,在两种不同的环境中,调控结构的功能相反,并可能提供B。burgdorferi的分子机制,以迅速适应不同的环境,在其地方性生活史。
During cycling between the tick vector and a mammal, the Lyme disease spirochaete Borrelia burgdorferi must coordinate expression of outer-surface proteins (Osps) A and B to quickly respond to environmental changes. The pathogen abundantly produces OspA/B in the tick, but represses their expression during mammalian infection. This paper reports a regulatory structure, consisting of two sequences flanking the ospAB promoter, that is required for enhancing ospA expression in B. burgdorferi grown in vitro, but repressing its expression during murine infection. Deletion or replacement of either the upstream or downstream sequence of the ospAB promoter caused a significant decrease in ospA expression in vitro, but a dramatic increase during murine infection. Fusion of either sequence with the flaB reporter promoter led to increased expression of an ospA reporter gene in vitro, but a decrease in the murine host. Furthermore, simultaneous fusion of both sequences with the reporter promoter showed a synergistic effect in enhancing expression of the ospA reporter in vitro, but repressing its expression during murine infection. Taken together, the results demonstrate that the regulatory structure functions oppositely in the two different environments and potentially provides B. burgdorferi with a molecular mechanism to quickly adapt to the distinct environments during its enzootic life cycle.
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