结核菌抑制宿主DNA修复,以提高其细胞内生存率
Shanshan Liu1, Liru Guan1, Cheng Peng1
1Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Tongji University School of Medicine, Shanghai 200433, P.R. China; Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
Cell host & microbe
|October 17, 2023
概括
结核菌抑制宿主DNA的修复,产生脂质滴滴用于复制. 准细菌尿素酶C阻断了这一过程,损害了细菌的生长.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 结核菌菌 (Mtb) 感染导致巨细胞中的脂质液滴形成,为细菌生长提供营养.
- Mtb操纵宿主细胞以创建这些富含脂质的利基的精确机制尚未完全理解.
研究的目的:
- 阐明Mtb在巨细胞中促进脂质液滴形成的分子机制.
- 为了确定参与操纵宿主DNA修复途径的细菌因素,用于Mtb复制.
主要方法:
- 研究了细菌尿酶C (UreC) 在Mtb诱导的宿主细胞变化中的作用.
- 利用分子生物学技术研究DNA修复复合体的形成和干扰素通路的激活.
- 评估尿酶抑制对MTB生长的 in vitro 和 in vivo 影响.
主要成果:
- Mtb通过UreC与RUVBL2相互作用来抑制宿主DNA的修复,防止RUVBL1-RUVBL2-RAD51复合体的形成.
- 抑制的DNA修复导致微核的形成,激活cGAS/STING通路和干扰素β (IFN-β) 的产生.
- IFN-β上调清洁者受体-A1 (SR-A1),促进脂肪滴形成,支持Mtb复制.
- 抑制UreC显著降低了巨细胞和体内生物中的Mtb生长.
结论:
- Mtb利用UreC来破坏宿主DNA修复,触发一连串导致脂质滴积累和有利的复制.
- 向细菌尿酶通过破坏其营养获取和复制周期,为对抗Mtb感染提供了潜在的治疗策略.
相关概念视频
01:31Defense Against Bacterial Pathogens
1.4K
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...
1.4K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:29Pulmonary Tuberculosis I
246
Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
246
01:18Other Unique Bacteria
19
Magnetic bacteria exhibit a directed movement called magnetotaxis, driven by structures called magnetosomes. These magnetosomes consist of chains of magnetic particles made of either magnetite (Fe₃O₄) or greigite (Fe₃S₄) and are organized in a linear conformation by a protein scaffold within invaginations of the cell membrane. The bacteria align along the north–south magnetic field lines, much like a compass needle. They are typically microaerophilic or anaerobic...
19
01:20Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
01:28Pulmonary Tuberculosis II
243
Tuberculosis, or TB, is a bacterial infectious disease caused by Mycobacterium tuberculosis. While its primary impact is on the lungs, leading to pulmonary tuberculosis, it can also affect various other organs, a condition referred to as extrapulmonary tuberculosis.
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
243