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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： Si Chen;Yuxin Liu;Yang Gao;Dong Zhang;Ru Zhang;Fei Tu;Nan Li;Qingkui Jiang;Linna Liu;Yanling Yang

作者机构：

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

期刊名称： Veterinary Microbiology

ISSN： 0378-1135

年卷期： 2025 年 307 卷

页码：

收录情况： SCIE（2025版）

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-ΔUGPase 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-ɑ, IFN-γ, and IL-2) and downregulation 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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