State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Nat Commun. 2024 Aug 16;15(1):7062. doi: 10.1038/s41467-024-50959-w.
Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC, encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes.
蛋白质的 O-链接 N-乙酰葡萄糖胺（O-GlcNAc）的翻译后添加通常与真核生物中的各种应激反应和细胞过程有关，但它在细菌中的潜在作用尚不清楚。在这里，我们表明蛋白 HmwC 作为一种 O-GlcNAc 转移酶（OGT），负责鼠疫耶尔森菌（一种由跳蚤传播的病原体，可引起鼠疫）中多种蛋白质的 O-GlcNAcylation。我们鉴定了 64 种在模拟哺乳动物宿主（Mh）和跳蚤载体（Fv）环境的条件下丰度不同的 O-GlcNAcylated 蛋白质（包括 65 个位点）。编码假定的 OGT 的 hmwC 缺失，与 GT41 家族的任何现有成员在结构上都不同，导致 O-GlcNAcylation 减少、生长减少以及在应激下毒力特性和存活能力改变。用 UDP-GlcNAc 作为糖供体，可在体外纯化 HmwC 修饰靶蛋白。靶蛋白之一 OsdY 促进鼠疫耶尔森菌在氧化应激条件下的存活。因此，我们的结果支持通过 O-GlcNAcylation 调节抗氧化反应可能是原核生物和真核生物共有的保守过程。
