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推测黄嘌呤脱氢酶对蜱虫和小鼠的生存至关重要。

A putative xanthine dehydrogenase is critical for survival in ticks and mice.

机构信息

Tufts University, Department of Molecular Biology and Microbiology, Boston, Massachusetts, USA.

Tufts University, Tufts Lyme Disease Initiative, Boston, Massachusetts, USA.

出版信息

Microbiology (Reading). 2023 Jan;169(1). doi: 10.1099/mic.0.001286.

Abstract

is a pathogenic bacterium and the causative agent of Lyme disease. It is exposed to reactive oxygen species (ROS) in both the vertebrate and tick hosts. While some mechanisms by which ameliorates the effects of ROS exposure have been studied, there are likely other unknown mechanisms of ROS neutralization that contribute to virulence. Here, we follow up on a three gene cluster of unknown function, and that our prior unbiased transposon insertional sequencing studies implicated in both ROS survival and survival in . We confirmed these findings through genetic knockout and provide evidence that these genes are co-transcribed as an operon to produce a xanthine dehydrogenase. In agreement with these results, we found that exposure to either uric acid (a product of xanthine dehydrogenase) or allopurinol (an inhibitor of xanthine dehydrogenase) could modulate sensitivity to ROS in a dependent manner. Together, this study identifies a previously uncharacterized three gene operon in as encoding a putative xanthine dehydrogenase critical for virulence. We propose renaming this locus .

摘要

是一种致病细菌,也是莱姆病的病原体。它在脊椎动物和蜱宿主中都会暴露于活性氧(ROS)。虽然已经研究了一些减轻 ROS 暴露影响的机制,但可能还有其他未知的 ROS 中和机制有助于毒力。在这里,我们研究了一个功能未知的三基因簇 和 ,我们之前的无偏转座子插入测序研究表明,它们与 ROS 存活和 在 中的存活都有关系。我们通过遗传敲除证实了这些发现,并提供了证据表明这些基因作为操纵子共同转录,产生黄嘌呤脱氢酶。与这些结果一致,我们发现 暴露于尿酸(黄嘌呤脱氢酶的产物)或别嘌呤醇(黄嘌呤脱氢酶的抑制剂)都可以以依赖于 的方式调节对 ROS 的敏感性。总之,这项研究鉴定了 中以前未被描述的编码潜在黄嘌呤脱氢酶的三个基因操纵子,该酶对毒力至关重要。我们建议重新命名这个基因座为.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d46/9993122/0f80339c45e3/mic-169-1286-g001.jpg

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