Genomics ( IF 4.4 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.ygeno.2020.09.010 Neha Jain 1 , Subodh Kumar Mishra 1 , Uma Shankar 1 , Ankit Jaiswal 1 , Tarun Kumar Sharma 2 , Prashant Kodgire 1 , Amit Kumar 1
The G-quadruplex structure is a highly conserved drug target for preventing infection of several human pathogens. We tried to explore G-quadruplex forming motifs as promising drug targets in the genome of Salmonella enterica that causes enteric fever in humans. Herein, we report three highly conserved G-quadruplex motifs (SE-PGQ-1, 2, and 3) in the genome of Salmonella enterica. Bioinformatics analysis inferred the presence of SE-PGQ-1 in the regulatory region of mgtA, SE-PGQ-2 in ORF of entA, and SE-PGQ-3 in the promoter region of malE and malK genes. The G-quadruplex forming sequences were confirmed by biophysical and biomolecular techniques. Cellular studies affirm the inhibitory effect of G-quadruplex specific ligands on Salmonella enterica growth. Further, PCR inhibition, reporter based assay, and RT-qPCR assays emphasize the biological relevance of G-quadruplexes in these genes. Thus, this study confirmed the presence of G-quadruplex motifs in Salmonella enterica and characterized them as a promising drug target.
中文翻译:
离子和麦芽糖转运蛋白基因中的 G-四链体稳定抑制沙门氏菌的生长和毒力。
G-四链体结构是一种高度保守的药物靶点,用于预防几种人类病原体的感染。我们试图探索 G-四链体形成基序作为引起人类肠道热的肠道沙门氏菌基因组中的有希望的药物靶点。在此,我们报告了肠道沙门氏菌基因组中的三个高度保守的 G-四链体基序(SE-PGQ-1、2 和 3)。生物信息学分析推断,在mgtA的调控区存在SE-PGQ-1,在entA的ORF中存在SE-PGQ-2,在malE和malK的启动子区存在SE-PGQ-3基因。G-四链体形成序列通过生物物理和生物分子技术得到证实。细胞研究证实了 G-四链体特异性配体对沙门氏菌生长的抑制作用。此外,PCR 抑制、基于报告基因的检测和 RT-qPCR 检测强调了 G-四链体在这些基因中的生物学相关性。因此,这项研究证实了肠道沙门氏菌中 G-四链体基序的存在,并将它们定性为一个有前途的药物靶点。