The Treponema pallidum Outer Membrane.
The Treponema pallidum Outer Membrane.
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DOI：
10.1007/82_2017_44
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发表时间：
2018
影响因子：
--
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Radolf JD;Kumar S
梅毒螺旋体的外膜（OM）是不可培养的性梅毒病原体，长期以来一直是误解和争议的主题。几十年前，研究人员推测梅毒螺旋体表面抗原性差是其引起持续感染的基础，但他们错误地将这种神秘的特性归因于血清蛋白和粘多糖保护性外层的存在。随后的研究表明，OM 是抗体结合的屏障，它含有少量的整合膜蛋白，并且螺旋体的免疫原性脂蛋白主要是周质的。自从重组 DNA 技术出现以来，OM 的脆弱性、蛋白质含量低以及梅毒螺旋体和革兰氏阴性外膜蛋白 (OMP) 之间缺乏序列相关性，使得表征宿主-病原体界面分子的工作变得复杂。我们利用基因组序列与计算工具相结合，克服了这些障碍，以识别预测形成β-桶的蛋白质，β-桶是双膜生物和进化相关的真核细胞器中OMP的标志构象。我们还采用了多种方法来确认一些候选 OMP 实际上确实形成两亲性 β-桶，并且在梅毒螺旋体中暴露于表面。这些研究建立了 BamA 的结构同源模型，并建立了梅毒螺旋体重复序列 (Tpr) 蛋白家族的二分拓扑。最近的生物信息学已经鉴定出几种已明确表征的革兰氏阴性 OMP 的结构直系同源物，表明梅毒螺旋体 OMP 库比以前认为的更类似于革兰氏阴性菌。螺旋体表面的脂蛋白粘附素和蛋白酶也可能有助于疾病发病机制和保护性免疫。
The outer membrane (OM) of Treponema pallidum, the uncultivatable agent of venereal syphilis, has long been the subject of misconceptions and controversy. Decades ago, researchers postulated that T. pallidum’s poor surface antigenicity is the basis for its ability to cause persistent infection, but they mistakenly attributed this enigmatic property to the presence of a protective outer coat of serum proteins and mucopolysaccharides. Subsequent studies revealed that the OM is the barrier to antibody binding, that it contains a paucity of integral membrane proteins, and that the preponderance of the spirochete’s immunogenic lipoproteins is periplasmic. Since the advent of recombinant DNA technology, the fragility of the OM, its low protein content, and the lack of sequence relatedness between T. pallidum and Gram-negative outer membrane proteins (OMPs) have complicated efforts to characterize molecules residing at the host–pathogen interface. We have overcome these hurdles using the genomic sequence in concert with computational tools to identify proteins predicted to form β-barrels, the hallmark conformation of OMPs in double-membrane organisms and evolutionarily related eukaryotic organelles. We also have employed diverse methodologies to confirm that some candidate OMPs do, in fact, form amphiphilic β-barrels and are surface-exposed in T. pallidum. These studies have led to a structural homology model for BamA and established the bipartite topology of the T. pallidum repeat (Tpr) family of proteins. Recent bioinformatics has identified several structural orthologs for well-characterized Gram-negative OMPs, suggesting that the T. pallidum OMP repertoire is more Gram-negative-like than previously supposed. Lipoprotein adhesins and proteases on the spirochete surface also may contribute to disease pathogenesis and protective immunity.
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影响因子：
3.1
作者：
ALDERETE, JF;BASEMAN, JB
通讯作者：
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Brautigam, Chad A.;Deka, Ranjit K.;Schuck, Peter;Tomchick, Diana R.;Norgard, Michael V.
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