Kraski Angelina, Mousavi Soraya, Heimesaat Markus M, Bereswill Stefan, Einspanier Ralf, Alter Thomas, Gölz Greta, Sharbati Soroush
Institute of Veterinary Biochemistry, Freie Universität Berlin, Berlin, Germany.
Institute of Microbiology, Infectious Diseases and Immunology, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Berlin, Germany.
Gut Pathog. 2023 Oct 17;15(1):48. doi: 10.1186/s13099-023-00577-6.
Zoonotic microorganisms are increasingly impacting human health worldwide. Due to the development of the global population, humans and animals live in shared and progressively crowded ecosystems, which enhances the risk of zoonoses. Although Campylobacter species are among the most important bacterial zoonotic agents worldwide, the molecular mechanisms of many host and pathogen factors involved in colonisation and infection are poorly understood. Campylobacter jejuni colonises the crypts of the human colon and causes acute inflammatory processes. The mucus and associated proteins play a central host-protective role in this process. The aim of this study was to explore the regulation of specific glycosyltransferase genes relevant to differential mucin-type O-glycosylation that could influence host colonisation and infection by C. jejuni.
Since microRNAs are known to be important regulators of the mammalian host cell response to bacterial infections, we focussed on the role of miR-125a-5p in C. jejuni infection. Combining in vitro and in vivo approaches, we show that miR-125a-5p regulates the expression of the sialyltransferase ST3GAL1 in an infection-dependent manner. The protein ST3GAL1 shows markedly increased intestinal levels in infected mice, with enhanced distribution in the mucosal epithelial layer in contrast to naïve mice.
From our previous studies and the data presented here, we conclude that miR-125a-5p and the previously reported miR-615-3p are involved in regulating the glycosylation patterns of relevant host cell response proteins during C. jejuni infection. The miRNA-dependent modulation of mucin-type O-glycosylation could be part of the mucosal immune response, but also a pathogen-driven modification that allows colonisation and infection of the mammalian host.
人畜共患微生物对全球人类健康的影响日益增大。由于全球人口的增长，人类和动物生活在共享且日益拥挤的生态系统中，这增加了人畜共患病的风险。尽管弯曲杆菌属是全球最重要的细菌性人畜共患病原体之一，但许多参与定植和感染的宿主及病原体因素的分子机制仍知之甚少。空肠弯曲杆菌定殖于人类结肠隐窝并引发急性炎症过程。黏液及相关蛋白在此过程中发挥着核心的宿主保护作用。本研究的目的是探索与差异黏蛋白型O-糖基化相关的特定糖基转移酶基因的调控，这些基因可能影响空肠弯曲杆菌对宿主的定植和感染。
由于已知微小RNA是哺乳动物宿主细胞对细菌感染反应的重要调节因子，我们聚焦于miR-125a-5p在空肠弯曲杆菌感染中的作用。结合体外和体内研究方法，我们发现miR-125a-5p以感染依赖的方式调节唾液酸转移酶ST3GAL1的表达。与未感染的小鼠相比，感染小鼠体内ST3GAL1蛋白在肠道中的水平显著升高，且在黏膜上皮层中的分布增强。
基于我们之前的研究以及本文所呈现的数据，我们得出结论，miR-125a-5p和先前报道的miR-615-3p参与调控空肠弯曲杆菌感染期间相关宿主细胞反应蛋白的糖基化模式。miRNA依赖的黏蛋白型O-糖基化调节可能是黏膜免疫反应的一部分，也是病原体驱动的一种修饰，它使得哺乳动物宿主能够被定植和感染。
