a Department of Genetics, Faculty of Biology , Sofia University "St. Kliment Ohridski" , Sofia , Bulgaria.
Expert Opin Ther Targets. 2019 Jul;23(7):631-643. doi: 10.1080/14728222.2019.1618274. Epub 2019 May 14.
: A constantly growing number of antibiotic-resistant strains of human pathogenic bacteria is an acute problem. Prolonged illnesses and increasing mortality worldwide mean that there is an urgent need to develop novel antibacterial drugs based on new targets and mechanisms of action. We present analyses of bacterial riboswitches that may be suitable as antibacterial drug targets. : Most bacterial riboswitches are allosteric cis-acting gene control elements located in the 5'-untranslated region of messenger RNAs. Riboswitches sense specific metabolites and regulate the synthesis of some essential cellular metabolites in many pathogenic bacteria but are not found in humans. We present a complete and comprehensive genome-wide bioinformatics analyses of the suitability of eight riboswitches as antibacterial drug targets in various pathogenic bacteria. : Based on our analyses, we classify the riboswitches in four different groups based on their suitability to be used as antibacterial drug targets. We have estimated that FMN, SAM-I, glmS, TPP, and Lysine riboswitches are promising targets for antibacterial drug discovery. : This research enables us to focus antibacterial drug discovery research only on those riboswitches whose inhibition will result in suppression of the growth of certain pathogenic bacteria.
:不断增长的抗生素耐药菌株是一个严峻的问题。全球范围内的长期疾病和不断增加的死亡率意味着我们迫切需要开发基于新靶点和作用机制的新型抗菌药物。我们提出了一些细菌核糖开关的分析,这些核糖开关可能适合作为抗菌药物靶点。
:大多数细菌核糖开关是位于信使 RNA 5'-非翻译区的变构顺式作用基因控制元件。核糖开关可以感应特定的代谢物,并调节许多致病性细菌中一些必需细胞代谢物的合成,但在人类中不存在。我们对 8 种核糖开关作为各种致病菌中抗菌药物靶点的适用性进行了全面和综合的基因组生物信息学分析。
:基于我们的分析,我们根据它们作为抗菌药物靶点的适用性将核糖开关分为四类。我们估计 FMN、SAM-I、glmS、TPP 和赖氨酸核糖开关是抗菌药物发现的有前途的靶标。
:这项研究使我们能够将抗菌药物发现研究仅集中在那些抑制将导致某些致病菌生长受到抑制的核糖开关上。