Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete.
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete.
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DOI：
10.1038/s41598-017-01589-4
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发表时间：
2017-05-08
影响因子：
4.6
通讯作者：
Moriarty TJ
中科院分区：
文献类型：
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作者：
Kao WA;Pětrošová H;Ebady R;Lithgow KV;Rojas P;Zhang Y;Kim YE;Kim YR;Odisho T;Gupta N;Moter A;Cameron CE;Moriarty TJ
梅毒螺旋体梅毒是梅毒的病原体，是一种高度侵入性的螺旋体病原体，它利用脉管系统传播到全身。鉴定促进传播的细菌因子对梅毒疫苗的开发至关重要。传播的一个重要步骤是细菌粘附到血管表面，这是一个由细菌蛋白介导的过程，该过程可以承受血流（血管粘附素）施加在粘附键上的力。T.苍白球血管粘附素受到该病原体的不可培养性质的阻碍。我们通过表达T.苍白球粘附素Tp 0751（pallilysin）在可培养的伯氏疏螺旋体的粘附减毒菌株中。在代表毛细血管后微静脉条件的流体剪切应力下，Tp 0751将细菌-血管相互作用恢复到与感染性B所观察到的水平相似的水平。burgdorferi和表达B的功能获得性菌株。伯氏血管粘附素BBK 32.在生理剪切应力下TP 0751和BBK 32依赖性内皮相互作用的强度和稳定性相似，尽管稳定这些相互作用的机制不同。TP 0751表达也允许细菌与活小鼠中的毛细血管后小静脉相互作用，与BBK 32表达菌株一样有效。这些结果表明，Tp 0751可以作为血管粘附素发挥作用。
Treponema pallidum subsp. pallidum, the causative agent of syphilis, is a highly invasive spirochete pathogen that uses the vasculature to disseminate throughout the body. Identification of bacterial factors promoting dissemination is crucial for syphilis vaccine development. An important step in dissemination is bacterial adhesion to blood vessel surfaces, a process mediated by bacterial proteins that can withstand forces imposed on adhesive bonds by blood flow (vascular adhesins). The study of T. pallidum vascular adhesins is hindered by the uncultivable nature of this pathogen. We overcame these limitations by expressing T. pallidum adhesin Tp0751 (pallilysin) in an adhesion-attenuated strain of the cultivable spirochete Borrelia burgdorferi. Under fluid shear stress representative of conditions in postcapillary venules, Tp0751 restored bacterial-vascular interactions to levels similar to those observed for infectious B. burgdorferi and a gain-of-function strain expressing B. burgdorferi vascular adhesin BBK32. The strength and stability of Tp0751- and BBK32-dependent endothelial interactions under physiological shear stress were similar, although the mechanisms stabilizing these interactions were distinct. Tp0751 expression also permitted bacteria to interact with postcapillary venules in live mice as effectively as BBK32-expressing strains. These results demonstrate that Tp0751 can function as a vascular adhesin.