State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
New Product R&D, GenScript Biotech Corporation, Nanjing 211100, China.
Nucleic Acids Res. 2024 Feb 28;52(4):1645-1660. doi: 10.1093/nar/gkad1172.
H-NS, the histone-like nucleoid-structuring protein in bacteria, regulates the stability of the bacterial genome by inhibiting the transcription of horizontally transferred genes, such as the type III and type VI secretion systems (T3/T6SS). While eukaryotic histone posttranslational modifications (PTMs) have been extensively studied, little is known about prokaryotic H-NS PTMs. Here, we report that the acetylation of H-NS attenuates its ability to silence horizontally transferred genes in response to amino acid nutrition and immune metabolites. Moreover, LC-MS/MS profiling showed that the acetyllysine sites of H-NS and K120 are indispensable for its DNA-binding ability. Acetylation of K120 leads to a low binding affinity for DNA and enhances T3/T6SS expression. Furthermore, acetylation of K120 impairs the AT-rich DNA recognition ability of H-NS. In addition, lysine acetylation in H-NS modulates in vivo bacterial virulence. These findings reveal the mechanism underlying H-NS PTMs and propose a novel mechanism by which bacteria counteract the xenogeneic silencing of H-NS.
H-NS，细菌中的组蛋白样核结构蛋白，通过抑制水平转移基因（如 III 型和 VI 型分泌系统（T3/T6SS））的转录来调节细菌基因组的稳定性。虽然真核组蛋白的翻译后修饰（PTMs）已经得到了广泛的研究，但原核 H-NS PTMs 的研究却知之甚少。在这里，我们报告 H-NS 的乙酰化作用减弱了其在氨基酸营养和免疫代谢物存在下沉默水平转移基因的能力。此外，LC-MS/MS 分析显示，H-NS 和 K120 的乙酰化赖氨酸位点对于其 DNA 结合能力是不可或缺的。K120 的乙酰化导致 DNA 的结合亲和力降低，并增强了 T3/T6SS 的表达。此外，K120 的乙酰化会损害 H-NS 对富含 AT 的 DNA 的识别能力。此外，H-NS 中的赖氨酸乙酰化调节了细菌的体内毒力。这些发现揭示了 H-NS PTMs 的机制，并提出了一种细菌对抗 H-NS 异源沉默的新机制。
