National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
mSystems. 2024 Oct 22;9(10):e0089324. doi: 10.1128/msystems.00893-24. Epub 2024 Sep 6.
can cause a rare, yet potentially fatal, central nervous system infection. NbtS protein may be a key virulence factor in infection of the brain. In this study, we investigated the function of the virulence-associated factor NbtS in microglial cells and in infected mice . We explored the interactions between NbtS and microglial cells (BV2 and human microglial clone 3), revealing that NbtS activates the toll-like receptor 4-dependent MyD88-IRAK4-IRAK1 and MAPK/nuclear factor kappa B (NF-κB) pathways, significantly enhancing pro-inflammatory responses as indicated by increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), as measured by ELISA and quantitative PCR. Apoptosis was elevated in these cells, as shown by increased expression of Bax and caspase-3 and decreased Bcl-2 levels. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay also confirmed the occurrence of apoptosis. In vivo, mice infected with an -deficient strain of exhibited higher survival rates and reduced brain inflammation, suggesting a pivotal role for the NbtS protein in the pathogenesis of . Conservation of the gene across spp. was verified by PCR, and the immunogenic potential of NbtS was confirmed by Western blot analysis using sera from infected mice. These findings suggest that targeting NbtS may offer a novel therapeutic strategy against infection.
The study presented in this article delves into the molecular underpinnings of -induced neuroinflammation. By focusing on the salicylate synthase gene, , and its encoded protein, NbtS, we uncover a pivotal virulence factor that triggers a cascade of immunological responses leading to apoptosis in microglial cells. This research not only enhances our comprehension of the pathogenesis of infections but also provides a potential therapeutic target. Given the rising importance of understanding host-microbe interactions within the context of the central nervous system, especially in immunocompromised individuals, the findings are of significant relevance to the field of microbiology and could inform future diagnostic and treatment modalities for -associated neurological disorders. Our work emphasizes the need for continued research into the intricate mechanisms of microbial pathogenesis and the development of novel strategies to combat life-threatening infections.
可引起罕见但潜在致命的中枢神经系统感染。NbtS 蛋白可能是 感染大脑的关键毒力因子。在这项研究中，我们研究了毒力相关因子 NbtS 在小神经胶质细胞和感染小鼠中的功能。我们探讨了 NbtS 与小神经胶质细胞（BV2 和人小神经胶质克隆 3）之间的相互作用，结果表明 NbtS 激活了 Toll 样受体 4 依赖性 MyD88-IRAK4-IRAK1 和 MAPK/核因子 kappa B（NF-κB）途径，显著增强了促炎反应，如 ELISA 和定量 PCR 所示，肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平增加。这些细胞中的细胞凋亡增加，如 Bax 和半胱天冬酶-3 的表达增加和 Bcl-2 水平降低所示。末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定也证实了细胞凋亡的发生。在体内，感染 缺失株的小鼠存活率更高，大脑炎症减轻，表明 NbtS 蛋白在 的发病机制中起关键作用。通过 PCR 验证了 across 种的 基因保守性，并通过使用感染小鼠的血清进行 Western blot 分析证实了 NbtS 的免疫原性。这些发现表明，针对 NbtS 可能为 感染提供一种新的治疗策略。
本文研究深入探讨了 诱导的神经炎症的分子基础。通过关注柳氮磺胺吡啶合酶基因 及其编码的蛋白 NbtS，我们发现了一种关键的毒力因子，它触发了一系列免疫反应，导致小神经胶质细胞凋亡。这项研究不仅增强了我们对 感染发病机制的理解，而且为治疗提供了一个潜在的靶点。鉴于了解中枢神经系统内宿主-微生物相互作用的重要性不断增加，特别是在免疫功能低下的个体中，这些发现与微生物学领域密切相关，并可能为与 相关的神经障碍的诊断和治疗模式提供信息。我们的工作强调了需要继续研究微生物发病机制的复杂机制，并制定新的策略来对抗危及生命的感染。
