The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii.
The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii.
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DOI：
10.1371/journal.ppat.1010370
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发表时间：
2022-03
期刊：
影响因子：
6.7
通讯作者：
Gherardini FC
中科院分区：
文献类型：
--
作者：
Richards CL;Raffel SJ;Bontemps-Gallo S;Dulebohn DP;Herbert TC;Gherardini FC
疏螺旋体属物种是氨基酸营养缺陷型生物，其利用通过其寡肽转运系统获得的二肽和三肽来供应氨基酸用于其地方流行周期期间的复制生长。然而，来自莱姆病（LD）和回归热（RF）组的疏螺旋体物种具有氨基酸转运和催化系统，精氨酸脱亚胺酶系统（ADI），其可能增加细胞内生长所需的L-精氨酸。RF螺旋体含有“完整的”四个基因ADI（arcA、B、D和C），而LD螺旋体具有arcA、B，有时具有D，但缺乏arcC（编码氨基甲酸酯激酶）。在这项研究中，我们评估了ADI系统在细菌存活和毒力中的作用，并发现RF和LD ADI的重要差异。在体外和小鼠感染模型中，B. hermsii细胞显著降低细胞外L-精氨酸水平，且该降低依赖于精氨酸脱亚胺酶表达。相反，B. burgdorferi在体外生长实验期间和感染哺乳动物宿主期间都没有降低L-精氨酸的浓度，这表明与B相比，直接利用L-精氨酸的能力存在根本差异。赫姆斯。进一步的实验使用在B. burgdorferi和B. hermsii，确定了生长特性和ADI转录和蛋白质表达的重要差异。我们还发现ADI系统在RF螺旋体的血液和脾脏定殖中起关键作用。在这项研究中，我们已经确定了两种密切相关的人类病原体的不同代谢策略，最终影响感染过程中的宿主-病原体界面。在美国，蜱传疾病的报告一直在稳步增加，由B。自1990年代末以来，burgdorferi增加了两倍。虽然不太常见，但由B引起的蜱传回归热病例。hermsii和B.在美国，通货膨胀率也在上升。虽然由不同的蜱传播并维持在独特的地方性流行周期中，但密切相关的螺旋体B。burgdorferi和B. Hermsii共有许多遗传特征，包括代谢活性截短和流线型能力。在这项研究中，我们结合联合收割机遗传和生化检测来确定ADI在B感染周期中的作用。burgdorferi和B.赫姆斯。当我们比较B。burgdorferi和B. hermsii，我们确定了它们各自ADI的重要差异，包括操纵子排列、对L-精氨酸和L-鸟氨酸水平的敏感性以及基因和蛋白质表达。此外，我们表明，精氨酸脱亚胺酶是必需的，以减少宿主L-精氨酸水平在小鼠感染B。赫姆斯。这项研究为两种医学相关螺旋体的代谢活动提供了新的见解，并突出了宿主-病原体相互作用的动态性质。
Borrelia species are amino acid auxotrophs that utilize di- and tri- peptides obtained through their oligopeptide transport system to supply amino acids for replicative growth during their enzootic cycles. However, Borrelia species from both the Lyme disease (LD) and relapsing fever (RF) groups harbor an amino acid transport and catabolism system, the Arginine Deiminase System (ADI), that could potentially augment intracellular L-arginine required for growth. RF spirochetes contain a “complete”, four gene ADI (arcA, B, D, and C) while LD spirochetes harbor arcA, B, and sometimes D but lack arcC (encoding carbamate kinase). In this study, we evaluated the role of the ADI system in bacterial survival and virulence and discovered important differences in RF and LD ADIs. Both in vitro and in a murine model of infection, B. hermsii cells significantly reduced extracellular L-arginine levels and that reduction was dependent on arginine deiminase expression. Conversely, B. burgdorferi did not reduce the concentration of L-arginine during in vitro growth experiments nor during infection of the mammalian host, suggesting a fundamental difference in the ability to directly utilize L-arginine compared to B. hermsii. Further experiments using a panel of mutants generated in both B. burgdorferi and B. hermsii, identified important differences in growth characteristics and ADI transcription and protein expression. We also found that the ADI system plays a key role in blood and spleen colonization in RF spirochetes. In this study we have identified divergent metabolic strategies in two closely related human pathogens, that ultimately impacts the host-pathogen interface during infection. Reports of tick-borne diseases have been steadily increasing in the US and the number of Lyme disease cases caused by B. burgdorferi have tripled since the late 1990’s. Although less common, cases of tick-borne relapsing fever, caused by B. hermsii and B. turicatae in the US, have increased as well. While transmitted by different ticks and maintained in unique enzootic cycles, the closely related spirochetes B. burgdorferi and B. hermsii share numerous genetic features including a truncated and streamlined capacity for metabolic activity. In this study we combine genetic and biochemical assays to define the role of the ADI in the infective cycles of B. burgdorferi and B. hermsii. When we compared B. burgdorferi and B. hermsii, we identified important differences in their respective ADI’s including operon arrangement, sensitivity to L-arginine and L-ornithine levels, as well as gene and protein expression. In addition, we show that arginine deiminase is required to reduce host L-arginine levels during murine infection with B. hermsii. This study provides new insights into the metabolic activities of two medically relevant spirochetes and highlights the dynamic nature of host-pathogen interactions.
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影响因子：
3.7
作者：
CHESEBRO, B;PORTIS, JL;NISHIO, J
通讯作者：
NISHIO, J
影响因子：
5.2
作者：
Desriac N;Broussolle V;Postollec F;Mathot AG;Sohier D;Coroller L;Leguerinel I
通讯作者：
Leguerinel I
影响因子：
5.4
作者：
BULLER, RS;AHMED, A;PORTIS, JL
通讯作者：
PORTIS, JL
影响因子：
3.1
作者：
Cusumano, Zachary T.;Watson, Michael E., Jr.;Caparon, Michael G.
通讯作者：
Caparon, Michael G.
影响因子：
6.7
作者：
Das P;Lahiri A;Lahiri A;Chakravortty D
通讯作者：
Chakravortty D