Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India.
Translational Health Science and Technology Institute, Faridabad, Haryana 121001, India.
Genomics. 2020 Nov;112(6):4863-4874. doi: 10.1016/j.ygeno.2020.09.010. Epub 2020 Sep 6.
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.
四链体结构是一种高度保守的药物靶点，可用于预防多种人类病原体的感染。我们试图探索肠沙门氏菌基因组中作为有前途的药物靶点的四链体形成基序，肠沙门氏菌会引起人类患肠热病。在此，我们报告了肠沙门氏菌基因组中三个高度保守的四链体基序（SE-PGQ-1、2 和 3）。生物信息学分析推断 SE-PGQ-1 存在于 mgtA 基因的调控区，SE-PGQ-2 存在于 entA 基因的 ORF 中，SE-PGQ-3 存在于 malE 和 malK 基因的启动子区。通过生物物理和生物分子技术证实了四链体形成序列的存在。细胞研究证实了四链体特异性配体对肠沙门氏菌生长的抑制作用。此外，PCR 抑制、基于报告基因的测定和 RT-qPCR 测定强调了这些基因中四链体的生物学相关性。因此，本研究证实了肠沙门氏菌中存在四链体基序，并将其表征为有前途的药物靶点。
