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UGPase: A novel molecule that regulates LPS synthesis, virulence, and immunogenicity of Brucella melitensis

文献类型： 外文期刊

作者： Chen, Si 1 ; Liu, Yuxin 1 ; Gao, Yang 1 ; Zhang, Dong 1 ; Zhang, Ru 1 ; Tu, Fei 2 ; Li, Nan 2 ; Jiang, Qingkui 3 ; Liu, Linna 4 ; Yang, Yanling 1 ;

作者机构： 1.Chinese Acad Agr Sci, Inst Special Anim & Plant Sci, State Key Lab Mol Biol Special Econ Anim, Changchun 130112, Peoples R China

2.Chinese Acad Agr Sci, Vet Res Inst, State Key Lab Pathogen & Biosecur, Key Lab Jilin Prov Zoonosis Prevent & Control, Changchun 130122, Peoples R China

3.Rutgers State Univ, Publ Hlth Res Inst, New Jersey Med Sch, Rutgers Biomed & Hlth Sci, Newark, NJ 08901 USA

4.Guangzhou Med Univ, Guangzhou Peoples Hosp 8, Guangzhou 510440, Peoples R China

关键词： Brucella melitensis; UTP-glucose-1-phosphate uridylyltransferase; Lipopolysaccharide; Virulence; Pathogenicity

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：2.7； 五年影响因子：2.9 ）

ISSN： 0378-1135

年卷期： 2025 年 307 卷

页码：

收录情况： SCI

摘要： UTP-glucose-1-phosphoryl transferase (UGPase) catalyzes the synthesis of UDP-glucose, a key precursor for glycogen production and an essential component in bacterial lipopolysaccharide (LPS) synthesis. In this study, we demonstrate that UGPase deletion significantly disrupted LPS synthesis in Brucella, leading to a phenotypic shift from a smooth to a rough type and a marked reduction in bacterial virulence. In vitro and in vivo experiments revealed that UGPase deletion impaired Brucella's ability to infect host cells and diminished its pathogenicity in mice. The deletion also significantly altered the LPS structure of the 16M-Delta UGPase strain, reducing its specific binding to Brucella-positive serum. Additionally, macrophages infected with the UGPase deletion mutant exhibited a decreased inflammatory response. In mice, infection with the mutant strain led to altered cytokine profiles, characterized by upregulation of pro-inflammatory markers (TNF-alpha, IFN-gamma, and IL-2) and down-regulation of anti-inflammatory markers (IL-10 and IL-4) compared to infections with the wild-type strain. This study identifies UGPase as a critical determinant of Brucella virulence and immunogenicity for the first time. The findings provide novel insights into the molecular mechanisms underlying Brucella pathogenesis and highlight UGPase as a promising target for the development of Brucella vaccines.

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