无机硫酸盐对于Mycobacterium tuberculosis肺组织殖民和氧化还原平衡至关重要
Wendy Le Mouëllic1, Florence Levillain1, Ting-Di Wu2
1Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse 31400, France.
概括
结核菌使用无机硫酸盐通过SubI-CysTWA输送器在感染期间生存. 这一途径对于维持氧化还原平衡至关重要,并为新的结核病疗法提供了潜在的目标.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 生物化学 生物化学
背景情况:
- 结核病 (TB) 是一种由Mycobacterium tuberculosis (Mtb) 引起的致命传染病.
- 了解Mtb代谢是开发新型抗结核治疗的关键.
- 硫对细菌生长,氧化还原平衡和辅酶生产至关重要,但Mtb的体内硫来源尚不清楚.
研究的目的:
- 为了确定Mtb在巨感染期间使用的主要硫源.
- 调查无机硫酸盐获取在Mtb病变和生存中的作用.
- 评估SubI-CysTWA传送器作为一个潜在的治疗目标.
主要方法:
- 纳米SIMS (纳米级二次离子质谱) 追踪硫同位素丰富 (33S) 在细胞内Mtb.
- 对subI基因的遗传删除,以评估对硫酸盐吸收和细菌生长的影响.
- 试验室和体内感染模型 (小鼠巨细胞,小鼠肺部) 来评估Mtb生存率和病变发生.
主要成果:
- 在巨菌感染期间,Mtb通过SubI-CysTWA载体获得无机硫酸盐.
- 硫酸盐的吸收对于mtb体外生长和巨细胞和小鼠肺部的生存至关重要.
- 硫酸盐的获取对于维护菌根细菌的氧化还原平衡和抵抗化应激至关重要.
结论:
- Mtb依赖于能源昂贵的无机硫酸盐同化,以在营养有限的宿主环境中生存,挑战了关于有机硫源的先前假设.
- 通过SubI-CysTWA介导的硫酸盐进口途径对于Mtb病原发生是必不可少的.
- 这一途径代表了新型抗结核治疗的有希望的,病原体特异性的治疗标.
相关概念视频
Sulfur Assimilation
321
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
321
Microbial Nutrition
1.1K
Organisms exhibit remarkable metabolic diversity, categorized based on how they acquire energy and carbon. These strategies enable survival in various ecological niches and are essential for maintaining energy flow and nutrient cycling within ecosystems.Energy and Carbon SourcesOrganisms are classified as phototrophs or chemotrophs based on energy acquisition. Phototrophs use light as their energy source, while chemotrophs rely on oxidizing chemical compounds. Further differentiation arises...
1.1K
Cell Inclusions
827
Prokaryotic cells possess a variety of inclusions that play crucial roles in nutrient storage, metabolic processes, and environmental adaptation. These structures enable bacteria to thrive under fluctuating environmental conditions by storing essential resources and optimizing their metabolic efficiency.Carbon Storage: Poly-β-Hydroxybutyric Acid and Glycogen GranulesBacteria frequently store excess carbon in specialized granules. Poly-β-hydroxybutyric acid (PHB) granules are lipid...
827
Oxygen Requirements and Growth Patterns
1.2K
Microorganisms exhibit diverse oxygen requirements and growth patterns driven by their metabolic strategies and environmental adaptations. Oxygen, while essential for many organisms, can also be toxic under certain conditions, shaping how microorganisms grow and survive.Oxygen Requirements of MicroorganismsMicroorganisms are classified based on their ability to use or tolerate oxygen:● Obligate aerobes like Mycobacterium tuberculosis need oxygen for energy production, as it serves as the...
1.2K
Carbon-dioxide Fixation
648
Carbon dioxide fixation in prokaryotes enables the assimilation of inorganic carbon into organic molecules, supporting biosynthetic pathways, sustaining ecosystems, and contributing to the global carbon cycle. It also has industrial applications in carbon capture and bioproduct synthesis. Autotrophic organisms rely on this process to utilize CO₂ as a carbon source in diverse environments.The Calvin CycleThe Calvin cycle is the most widespread carbon fixation mechanism, primarily used by...
648
Anoxygenic Photosynthesis
1.2K
Anoxygenic photosynthesis is a phototrophic process that captures light energy to drive carbon fixation without producing molecular oxygen. Unlike oxygenic photosynthesis, which utilizes water as an electron donor and releases oxygen, anoxygenic phototrophs use alternative electron donors such as hydrogen sulfide (H₂S), elemental sulfur (S⁰), or thiosulfate (S₂O₃²⁻). This process is carried out by diverse groups of bacteria, including purple bacteria, green...
1.2K


