Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, TAMU-4467, College Station, TX, 77843, USA.
Current affiliation: Department of Entomology, College of Agricultural and Life Sciences, Texas A&M University, College Station, USA.
BMC Microbiol. 2017 Nov 22;17(1):219. doi: 10.1186/s12866-017-1127-y.
The bacterial spirochete Borrelia burgdorferi is the causative agent of the most commonly reported arthropod-borne illness in the United States, Lyme disease. A family of proteins containing von Willebrand Factor A (VWFA) domains adjacent to a MoxR AAA+ ATPase have been found to be highly conserved in the genus Borrelia. Previously, a VWFA domain containing protein of B. burgdorferi, BB0172, was determined to be an outer membrane protein capable of binding integrin α3β1. In this study, the characterization of a new VWFA domain containing membrane protein, BB0173, is evaluated in order to define the location and topology of this multi-spanning membrane protein. In addition, functional predictions are made.
Our results show that BB0173, in contrast to BB0172, is an inner membrane protein, in which the VWFA domain is exposed to the periplasmic space. Further, BB0173 was predicted to have an aerotolerance regulator domain, and expression of BB0173 and the surrounding genes was evaluated under aerobic and microaerophilic conditions, revealing that these genes are downregulated under aerobic conditions. Since the VWFA domain containing proteins of B. burgdorferi are highly conserved, they are likely required for survival of the pathogen through sensing diverse environmental oxygen conditions.
Presently, the complex mechanisms that B. burgdorferi uses to detect and respond to environmental changes are not completely understood. However, studying the mechanisms that allow B. burgdorferi to survive in the highly disparate environments of the tick vector and mammalian host could allow for the development of novel methods of preventing acquisition, survival, or transmission of the spirochete. In this regard, a putative membrane protein, BB0173, was characterized. BB0173 was found to be highly conserved across pathogenic Borrelia, and additionally contains several truly transmembrane domains, and a Bacteroides aerotolerance-like domain. The presence of these functional domains and the highly conserved nature of this protein, strongly suggests a required function of BB0173 in the survival of B. burgdorferi.
细菌螺旋体伯氏疏螺旋体是美国最常见的节肢动物传播疾病莱姆病的病原体。含有血管性血友病因子 A (VWFA)结构域的蛋白家族与 MoxR AAA+ATP 酶相邻，在疏螺旋体属中高度保守。先前，伯氏疏螺旋体的一种含有 VWFA 结构域的蛋白 BB0172 被确定为能够结合整合素 α3β1 的外膜蛋白。在这项研究中，评估了一种新的含有 VWFA 结构域的膜蛋白 BB0173 的特性，以确定该多跨膜蛋白的位置和拓扑结构。此外，还进行了功能预测。
我们的结果表明，与 BB0172 相反，BB0173 是一种内膜蛋白，其中 VWFA 结构域暴露于周质空间。此外，BB0173 被预测具有耐气调节域，并且在需氧和微需氧条件下评估了 BB0173 和周围基因的表达，结果表明这些基因在需氧条件下下调。由于伯氏疏螺旋体的 VWFA 结构域蛋白高度保守，因此它们可能是病原体通过感知不同环境氧条件而存活所必需的。
目前，伯氏疏螺旋体用于检测和响应环境变化的复杂机制尚不完全清楚。然而，研究伯氏疏螺旋体用于在蜱载体和哺乳动物宿主的高度不同的环境中存活的机制，可以开发出防止螺旋体获得、存活或传播的新方法。在这方面，表征了一种假定的膜蛋白 BB0173。BB0173 在致病性疏螺旋体中高度保守，此外还含有几个真正的跨膜结构域和一个类拟杆菌耐气结构域。这些功能结构域的存在以及该蛋白的高度保守性，强烈表明 BB0173 在伯氏疏螺旋体的存活中具有必需的功能。
