Zhang Huan, Xing Yukai, Zhu Jinying, Wu Sijiao, Gao Jingbo, Wang Yuqi, Yu Ze, Li Ang, Li Yuzhuo, Chen Xiaoyue, Chen Zeliang
Key Laboratory of Livestock Infectious Disease, Ministry of Education, Shenyang Agricultural University, Shenyang 110866, China.
Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510275, China.
Int J Mol Sci. 2025 Apr 10;26(8):3573. doi: 10.3390/ijms26083573.
The type IV secretion system (T4SS) is an important virulence factor of . T4SS secretes 16 effector proteins, which affect the intracellular transport of -containing vacuoles and regulate the host immune response, helping survive and replicate in host cells. In our previous crotonylation proteomics data of HEK-293T cell proteins triggered by BspF, we found BspF crotonylated on TRIM38, which is an important modulator in the pathways of inflammation, and the crotonylation site is K142. Therefore, it is speculated that BspF may be involved in the regulation of host inflammatory response during infection. In this study, we found that BspF-mediated TRIM38K142 crotonylation promotes the ubiquitination of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6), leading to the degradation of TRAF6 and thereby inhibiting the transduction of Nuclear factor-kappaB (NF-κB), p38 Mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinases (JNK) MAPK signaling pathways and the secretion of pro-inflammatory factors and , which finally helps promote intracellular survival. This study provides a new theoretical basis for the intracellular survival of host innate immunity through the T4SS, provides new insights into the pathogenic mechanism and treatment of , and provides an important reference for the study of non-histone crotonylation function.
IV型分泌系统（T4SS）是[病原体名称未给出]的一种重要毒力因子。T4SS分泌16种效应蛋白，这些蛋白影响含[物质名称未给出]液泡的细胞内运输并调节宿主免疫反应，帮助[病原体名称未给出]在宿主细胞中存活和复制。在我们之前关于由BspF触发的HEK - 293T细胞蛋白质的巴豆酰化蛋白质组学数据中，我们发现BspF在TRIM38上发生了巴豆酰化，TRIM38是炎症途径中的一个重要调节因子，巴豆酰化位点是K142。因此，推测BspF可能在[病原体名称未给出]感染期间参与宿主炎症反应的调节。在本研究中，我们发现BspF介导的TRIM38K142巴豆酰化促进肿瘤坏死因子受体（TNFR）相关因子6（TRAF6）的泛素化，导致TRAF6降解，从而抑制核因子κB（NF - κB）、p38丝裂原活化蛋白激酶（MAPK）和c - Jun氨基末端激酶（JNK）MAPK信号通路的转导以及促炎因子[因子名称未给出]和[因子名称未给出]的分泌，最终有助于[病原体名称未给出]促进细胞内存活。本研究为通过T4SS实现宿主固有免疫的细胞内存活提供了新的理论依据，为[病原体名称未给出]的致病机制和治疗提供了新的见解，并为非组蛋白巴豆酰化功能的研究提供了重要参考。
