The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete.
The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete.
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DOI：
10.1371/journal.ppat.1009546
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发表时间：
2021-05
期刊：
影响因子：
6.7
通讯作者：
Jutras BL
中科院分区：
文献类型：
--
作者：
Davis MM;Brock AM;DeHart TG;Boribong BP;Lee K;McClune ME;Chang Y;Cramer N;Liu J;Jones CN;Jutras BL
导致莱姆病的细菌病原体，伯氏疏螺旋体，是一种非典型的革兰氏阴性螺旋体，通过感染的硬蜱叮咬传播给人类。在双胚层中，肽聚糖（PG）夹在细胞被膜的内膜和外膜之间。在许多其他革兰氏阴性细菌中，PG被蛋白质结合，这提供了包膜层之间的结构完整性和连续性。在这里，我们提出的证据肽聚糖相关蛋白（PAP）在B。burgdorferi。使用无偏见的蛋白质组学方法，我们确定了神经元吸引蛋白A（NapA）作为PAP。有趣的是，NapA是Dps同源物，其通常在应激期间起结合和保护细胞DNA免受损伤的作用。而B.已知BurgdorferiNapA参与氧化应激反应，但它缺乏DNA结合所必需的关键残基。生物化学和细胞研究表明NapA定位于B。burgdorferi周质，确实是PAP。冷冻电子显微镜表明，突变细菌，不能产生NapA，有结构异常。细胞壁完整性的缺陷会影响生长速率，并导致napA突变体对渗透压和PG特异性胁迫更敏感。与单独的PG相比，NapA连接的PG分泌在外膜囊泡中并增加IL-17的产生。使用微流体技术，我们证明NapA作为一个分子信标，加剧了B的致病特性。这些研究进一步加深了我们对B的理解。Burgdorferi细胞包膜，提供了其发病机制的关键信息，并强调了高度保守的细菌蛋白如何在维持生物学功能的同时进行机械进化。双胚层通常产生肽聚糖相关蛋白（PAP），以增强细胞包膜内的结构完整性和连续性。我们在B区发现了PAP。burgdorferi，与几乎普遍存在的细菌蛋白Dps（来自饥饿细菌的DNA结合蛋白）具有结构和序列同源性。B。BurgdorferiDps parasitic不能结合DNA。相反，它支持PG层的保护特性，同时在宿主免疫调节中发挥重要作用。总的来说，我们的研究结果突出了细菌蛋白质的可塑性，因为它们可能会改变它们执行任务的方式，尽管它们保持相同的基本生物功能。
The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Here, we present evidence of a peptidoglycan-associated protein (PAP) in B. burgdorferi. Using an unbiased proteomics approach, we identified Neutrophil Attracting Protein A (NapA) as a PAP. Interestingly, NapA is a Dps homologue, which typically functions to bind and protect cellular DNA from damage during times of stress. While B. burgdorferi NapA is known to be involved in the oxidative stress response, it lacks the critical residues necessary for DNA binding. Biochemical and cellular studies demonstrate that NapA is localized to the B. burgdorferi periplasm and is indeed a PAP. Cryo-electron microscopy indicates that mutant bacteria, unable to produce NapA, have structural abnormalities. Defects in cell-wall integrity impact growth rate and cause the napA mutant to be more susceptible to osmotic and PG-specific stresses. NapA-linked PG is secreted in outer membrane vesicles and augments IL-17 production, relative to PG alone. Using microfluidics, we demonstrate that NapA acts as a molecular beacon—exacerbating the pathogenic properties of B. burgdorferi PG. These studies further our understanding of the B. burgdorferi cell envelope, provide critical information that underlies its pathogenesis, and highlight how a highly conserved bacterial protein can evolve mechanistically, while maintaining biological function. Diderms typically produce peptidoglycan-associated proteins (PAPs) to enhance structural integrity and continuity within the cell envelope. We have identified a PAP in B. burgdorferi with structural and sequence homology to the near ubiquitous bacterial protein Dps (DNA binding protein from starved bacteria). The B. burgdorferi Dps paralogue is incapable of binding DNA. Instead, it bolsters the protective properties of the PG layer, while playing an important role in host immune modulation. Collectively, our findings highlight the plasticity of bacterial proteins in that they may change how they perform a task despite maintaining the same basic biological function.
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影响因子：
3.1
作者：
Feltcher ME;Sullivan JT;Braunstein M
通讯作者：
Braunstein M
影响因子：
6.7
作者：
Crowley JT;Toledo AM;LaRocca TJ;Coleman JL;London E;Benach JL
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Benach JL
影响因子：
4.5
作者：
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影响因子：
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作者：
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通讯作者：
de Bernard, Marina
影响因子：
3.2
作者：
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通讯作者：
Radolf, JD