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, Cape Town, South Africa.
Microbiology spectrum
|June 25, 2024
概括
结核菌可以制造 riboflavin (维生素 B2),对于细胞能量至关重要. 破坏其合成途径会杀死细菌,使其成为潜在的结核病药物标.
科学领域:
- 微生物学 微生物学
- 生物化学 生化学
- 免疫学 免疫学 免疫学
背景情况:
- рибофлавин (维生素B2) 对于通过FAD和FMN共酶的细胞氧化还原代谢至关重要.
- 结核菌 (Mtb) 与人类不同,合成利博,其通路中间体激活粘膜相关的不变T细胞 (MAIT).
- 了解Mtb的 рибофлавин通路对于结核病药物发现和MAIT细胞介导免疫的关键.
研究的目的:
- 调查MTB和Mycobacterium smegmatis (Msm) 中的利博弗拉及其中间体的生物合成和功能.
- 通过基因验证,将 riboflavin 途径作为结核病 (TB) 药物发现的潜在目标.
- 为研究 рибофлавин在 MAIT 细胞激活和结核病发病过程中的作用创建资源.
主要方法:
- 在 riboflavin 生合成和利用基因中使用可诱导的 CRISPR 干扰在 Msm 和 Mtb 中创建了有条件的淘汰 (hypomorphs).
- 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.
主要成果:
- 尽管缺乏正规输送体,但MSM和Mtb可以同化外源性 рибофлавин.
- 在MSM中观察到卢马合成酶的功能冗余性.
- 在Mtb中抑制ribA2或ribF是杀菌的.
- 在MSM中,ribA2沉默导致基因表达途径减少,蛋白质/ рибофлавин耗尽,并且具有杀菌作用.
结论:
- рибофлавин生物合成途径对Mtb活力至关重要,并且代表了针对抗结核药物开发的验证目标.
- 生成的hypomorph集合作为一个有价值的工具,用于进一步研究 riboflavin 代谢和 MAIT 细胞相互作用在菌根菌.
相关概念视频
Riboswitches
8.1K
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...
8.1K
Types of RNA
63.5K
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...
63.5K
Transcription Attenuation in Prokaryotes
15.3K
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...
15.3K
Prokaryotic Transcriptional Activators and Repressors
21.0K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
21.0K
Regulation of Expression at Multiple Steps
889
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
889


