Ma Zhongmei, Wei Lixiang, Wang Zhanpeng, Liu Yucheng, Li Nengxiu, Jiao Jian, Zuo Yufei, Xia Xianzhu, Cai Xuepeng, Meng Qingling, Qiao Jun
College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China.
State Key Laboratory for Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, Xinjiang 832000, China.
Int J Biol Macromol. 2025 Mar;292:139065. doi: 10.1016/j.ijbiomac.2024.139065. Epub 2024 Dec 24.
As important post-transcriptional regulators of gene expression, sRNAs play important modulatory roles in the environmental adaptation and virulence of bacteria. To investigate the regulatory role of sRNA STnc3020 in the virulence of Salmonella typhimurium (S. typhimurium). This study analyzed the impacts of STnc3020 deletion on adherence, invasion, intracellular survival, macrophage apoptosis, and pathogenicity of S. typhimurium in mice. Furthermore, potential regulatory target genes of STnc3020 were identified and its regulatory mechanism was validated. The results showed that at the cellular level, the deletion of STnc3020 significantly reduced the adhesion ability of S. typhimurium to intestinal epithelial cells (P < 0.01), as well as its proliferation and apoptosis-inducing abilities within macrophages (P < 0.01). Meanwhile, animal experiment results indicated that the deletion of STnc3020 significantly reduced the colonization rate of S. typhimurium in the liver and cecum of mice (P < 0.01), and increased the median lethal dose (4.28 × 10) in mice. Regulatory mechanism research results showed that STnc3020 can interact with the target gene prgJ of the Type III secretion system (T3SS), and the protein level of PrgJ significantly decreased after the deletion of STnc3020 (P < 0.01). These findings offer new insights into sRNA-mediated virulence control and may aid in developing new vaccines and drugs for S. typhimurium.
作为基因表达重要的转录后调节因子,小RNA(sRNA)在细菌的环境适应性和毒力方面发挥着重要的调节作用。为了研究sRNA STnc3020在鼠伤寒沙门氏菌(伤寒沙门氏菌)毒力中的调节作用,本研究分析了STnc3020缺失对伤寒沙门氏菌的黏附、侵袭、细胞内存活、巨噬细胞凋亡以及在小鼠体内致病性的影响。此外,还鉴定了STnc3020潜在的调控靶基因并验证了其调控机制。结果表明,在细胞水平上,STnc3020的缺失显著降低了伤寒沙门氏菌对肠上皮细胞的黏附能力(P < 0.01),以及其在巨噬细胞内的增殖和诱导凋亡能力(P < 0.01)。同时,动物实验结果表明,STnc3020的缺失显著降低了伤寒沙门氏菌在小鼠肝脏和盲肠中的定植率(P < 0.01),并增加了小鼠的半数致死剂量(4.28×10)。调控机制研究结果表明,STnc3020可与III型分泌系统(T3SS)的靶基因prgJ相互作用,STnc3020缺失后PrgJ的蛋白水平显著降低(P < 0.01)。这些发现为sRNA介导的毒力控制提供了新的见解,并可能有助于开发针对伤寒沙门氏菌的新型疫苗和药物。