一个可扩展的肠表皮有机体模型揭示了人类适应的病原体的全基因组殖民景观
Maria Letizia Di Martino1, Laura Jenniches2, Anjeela Bhetwal3
1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. ml.dimartino@imbim.uu.se.
Nature genetics
|June 12, 2025
概括
研究人员使用器官模型和先进的测序绘制了Shigella flexneri基因,这些基因对于感染人类肠道细胞至关重要. 这揭示了一个新的转录后控制机制,调节细菌毒性.
科学领域:
- 微生物学 微生物学
- 基因组学就是基因组学.
- 传染性疾病 传染性疾病
背景情况:
- 由于小型动物模型在复制人类生理学方面的局限性,研究像Shigella flexneri这样适应人类的病原体是很困难的.
- 对控制Shigella flexneri感染的遗传和调控机制的全面理解仍然不完整.
研究的目的:
- 为了创建一个全基因组的Shigella基因的地图,对于感染人类肠道上皮质至关重要.
- 为了识别涉及到Shigella病变的毒性因素和调节途径.
- 开发一个可扩展的框架来研究人与微生物的相互作用.
主要方法:
- 在大规模的Shigella感染中使用了有机体模型 (肠体和肠体).
- 使用转子子导向插入测序 (Tn-seq) 进行高通量遗传查.
- 应用贝叶斯统计建模来分析感染瓶和识别必要的基因.
主要成果:
- 产生了对人类肠道上皮细胞感染所需的Shigella基因的全面地图.
- 确定了在不同肠道区域和几何结构中对上皮细胞殖民至关重要的关键毒性作用因子.
- 发现了100多个染色体基因参与感染过程.
- 发现了一种涉及tRNA修饰和控制细菌毒性的编码子使用的转录后调节机制.
结论:
- 这项研究提供了对Shigella病毒性因素和监管网络的全基因组理解.
- 阐明了一种影响细菌毒性的新型转录后控制机制.
- 开发的整合有机体培养,功能基因组学和计算分析的框架广泛适用于研究宿主-病原体相互作用.
更多相关视频
相关概念视频
01:22Introduction to the Human Microbiota
Microorganisms colonize various regions of the human body, including the mouth, nasal passages, throat, stomach, intestines, urogenital tract, and skin. The total number of microbial cells is estimated to range from 10¹³ to 10¹⁴—comparable to, or exceeding, the number of human somatic cells. This host–microbiome relationship has led to the conceptualization of humans as supraorganisms, wherein microbial communities perform vital roles in development, immunity, and disease...
01:25Colonisation of Pathogens
Pathogen colonization of host tissues is a critical step in the development of infectious diseases. Various pathogenic microorganisms, including bacteria, fungi, viruses, and protozoa, have evolved complex strategies to attach to, invade, and persist within host environments. These mechanisms enable pathogens to establish infections, evade immune responses, and resist antimicrobial treatments.Attachment to Host CellsIn bacteria, colonization typically begins with adherence to host epithelial...