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针对FMN,TPP,SAM-I和glmS的Riboswitch与化学反意义寡核化物进行完全理性的抗菌药物开发

Nikolet Pavlova¹, Martina Traykovska¹, Robert Penchovsky¹

¹Laboratory of Synthetic Biology and Bioinformatics, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria.

Antibiotics (Basel, Switzerland)

|November 24, 2023

概括

针对细菌的核糖开关的化学反感性寡核酸为抗生素耐药性提供了一种新的方法. 这种方法对抗耐药菌株有效,对人体细胞无毒性.

科学领域:

微生物学微生物学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

抗微生物药物耐药性是全球主要的健康威胁.
丝带开关是细菌mRNA调节元件,控制基因表达.
准 рибо开关是开发新抗菌剂的有希望的策略.

研究的目的:

描述针对特定细菌核糖开关的仿真反意义寡核酸 (ASO) 的合理设计和应用.
为了评估ASOs与细胞透作为抗菌剂的有效性和安全性.
为了证明 рибо开关作为新型抗生素开发的目标的潜力.

主要方法:

进行全基因组生物信息分析,选择四个关键的核糖转换器 (glmS,FMN,TPP,SAM-I).
设计和合成与细胞透的寡酸pVEC结合的仿真反感性寡酸.
测试ASO对*黄金葡萄球菌*,*Listeria monocytogenes*和*大肠杆菌*的疗效.
在人类细胞系中评估ASO毒性.

主要成果:

ASO有效地准了格拉姆阳性和格拉姆阴性细菌中的选定的核糖开关.
平均700nM (4.5μg/mL) 的ASO剂量抑制了80%的细菌生长.
在有效度下,在人类细胞系中没有观察到显著的毒性.
证明了 рибо开关作为ASO基抗菌疗法的点的适用性.

结论:

针对特定的 рибо开关的仿真ASO的合理设计是对抗抗生素耐药细菌的可行策略.
这种方法为开发适应新兴耐药性的窄谱或宽谱抗生素提供了潜力.
针对 рибо开关的ASO技术代表了下一代抗菌治疗的创新途径.

关键词:

抗菌剂是一种抗菌剂.发现抗菌药物发现.反感的寡核化物.穿透细胞的类.毒品目标是毒品的目标.有理性的药物开发.带丝切换器带丝切换器

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Types of RNA

Types of RNA

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...

Riboswitches

Riboswitches

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...