菌根杆菌bovis frd操作子相变异劫持了顺序信号,以驱动免疫代谢重新连接和致病性
Yuhui Dong1, Xin Ge1, Qingbin Guo1
1State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Nature communications
|July 15, 2025
概括
结核菌利用基因变异来操纵宿主免疫力,导致严重的结核病. 了解这种机制为这种全球健康威胁提供了新的治疗点.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 结核病 (TB) 仍然是一个重大的全球卫生挑战,由结核菌复合体 (MTBC) 病原体引起.
- 细菌的遗传适应,特别是基因组同聚合物 (HT) 路径的相变化,在宿主感染期间与驱动病原性演变有关.
- 细菌毒性因子和宿主免疫代谢之间的复杂相互作用对于理解结核病原体至关重要.
研究的目的:
- 调查Mycobacterium bovis如何利用烟酸还原酶编码frd操作子中的同聚合物通道 (HT) 插入突变来颠覆宿主免疫代谢.
- 阐明细菌酸盐分泌在调节宿主免疫反应中的作用,特别是缺氧诱导因子-1α (HIF-1α) 和IL-1β信号通路.
- 探索这些细菌适应对免疫逃避策略和结核病潜在治疗干预措施的影响.
主要方法:
- 在巨细胞感染模型中对M. bovis frd operon HT插入突变的分析.
- 评估酸盐分泌,HIF-1α稳定和下游免疫信号 (IL-1β,Th1/Th17反应).
- 在小鼠感染模型中评估细菌病原性和肺病理,包括对IL-1R阻塞的实验.
主要成果:
- 野生型的M. bovis分泌糖,稳定HIF-1α以促进IL-1β的产生和Th1免疫力,从而抑制细菌的生长.
- M. bovis frd HT插入突变体表现出受损的酸盐分泌,导致抑制HIF-1α/IL-1β信号传递,并转向致病性Th17反应.
- 突变者在小鼠中表现出增强的致病性,增加了细菌负担和加剧的肺病理,模仿IL-1R阻塞的影响.
结论:
- M. bovis通过frd基因相变异劫持了酸盐/HIF-1α/IL-1β轴,以操纵宿主免疫力.
- 在临床M. tb孤立中保存的frd HT多态性表明MTBC病原体之间广泛的免疫逃避策略.
- 准宿主代谢检查点为开发新型结核病疗法提供了一个有希望的框架.
相关概念视频
Transcriptional Regulation: Riboswitches
121
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
121
Inducible Operons: lac Operon
161
The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA...
161
Gene Regulation in Microbial Communities: Quorum Sensing
96
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
96
Defense Against Bacterial Pathogens
1.5K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
1.5K
Transduction
120
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
120
Stringent Response in E. coli
56
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
56


