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Erythronate utilization activates VdtR regulating its metabolism to promote Brucella proliferation, inducing abortion in

文献类型： 外文期刊

作者： Yin, Yi;Fang, Tian;Lian, Zhengmin;Zuo, Dong;Hu, Hai;Zhang, Guangdong;Ding, Chan;Tian, Mingxing;Yu, Shengqing

作者机构：

关键词： Brucella;VdtR regulation;erythronate metabolic pathway;abortion

期刊名称： MICROBIOLOGY SPECTRUM

ISSN： 2165-0497

年卷期： 2023 年

页码：

收录情况： SCIE（2023版）

摘要： Brucella is a facultative intracellular pathogen that preferentially colonizes reproductive organs and utilizes erythritol as a preferred carbon source for its survival and proliferation. In this study, we identifiedidentified a virulence-related DeoR-family transcriptional regulator (VdtR) and an erythronate metabolic pathway responsible for four-carbon acid sugar metabolism of D-erythronate and L-threonate in Brucella. We found that VdtR plays an important role in Brucella intracellular survival and trafficking to the endoplasmic reticulum in RAW 264.7 macrophages and in virulence in a mouse model. More importantly, we found that VdtR negatively regulates the erythronate metabolic pathway to promote extracellular proliferation of Brucella, depending on utilization of D-erythronate, an oxidative product of erythritol in the host. In a pregnant mouse model, the erythronate metabolic pathway was shown to cooperate with erythritol metabolism and play a crucial role in Brucella proliferation in the placenta, inducing placentitis and finally resulting in abortion or stillbirth. Our results demonstrate that, in addition to erythritol, erythronate is a preferred carbon source for Brucella utilization to promote its extracellular proliferation. This discovery updates the information on the preferential colonization of reproductive organs by Brucella and provides a novel insight into the Brucella-associated induction of abortion in pregnant animals.

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