调节 рибофлавин 生物合成和利用在 菌根细菌 的调节
Melissa D Chengalroyen1, Carolina Mehaffy2, Megan Lucas2
1Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine & Department of Pathology, University of Cape Town, South Africa.
bioRxiv : the preprint server for biology
|September 11, 2023
概括
结核菌可以制造 riboflavin (维生素 B2),对于细胞能量至关重要. 沉默关键基因在这个途径是致命的mtb,提供潜在的新结核病药物标.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
背景情况:
- рибофлавин (维生素B2) 对于细胞的氧化还原代谢至关重要,由微生物如 Mycobacterium tuberculosis (Mtb) 合成.
- riboflavin 途径中间体激活粘膜相关的不变T细胞 (MAIT),将微生物代谢与免疫反应联系起来.
研究的目的:
- 研究 riboflavin 生合成和功能在菌根菌代谢和生理学.
- 分析 riboflavin 途径中间体在 MAIT 细胞识别中的作用.
- 在Mycobacterium smegmatis (Msm) 和Mtb.中创建和利用条件基因淘汰 (低形态)
主要方法:
- 构造可诱导的CRISPR干扰在Msm和Mtb.中的 рибофлавин生物合成和利用基因中的低形态.
- 分析了基因沉默对细菌活力,基因转录,蛋白质水平和 рибофлавин度的影响.
- 在MSM和MTB中评估了外源性 рибофлавин的同化.
主要成果:
- 无论是MSM还是Mtb,都能同化外源性 рибофлавин,即使没有正规输送器.
- 在MSM中观察到卢马合成酶活性的功能冗余性.
- 沉默ribA2或ribF基因被证明是对Mtb的高度杀菌.
- 在MSM中,ribA2沉默导致了广泛的通路基因敲击,RibA2枯竭, рибофлавин枯竭,并且是杀菌的.
结论:
- 这项研究验证了 riboflavin 生合成基因作为结核病治疗的潜在药物标.
- 生成的低形态集合作为一种有价值的工具,用于研究菌体生理学和MAIT细胞激活中的利博弗拉通路作用.
相关概念视频
Transcriptional Regulation: Riboswitches
61
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...
61
Riboswitches
8.2K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.2K
Types of RNA
63.9K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
63.9K
Biosynthesis in Bacteria
39
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
39
Transcription Attenuation in Prokaryotes
15.4K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.4K
Translational Regulation
42
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
42


