G-quadruplex stabilization in the ions and maltose transporters gene inhibit Salmonella enterica growth and virulence

离子和麦芽糖转运蛋白基因中的 G-四链体稳定可抑制肠道沙门氏菌的生长和毒力

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作者:Neha Jain, Subodh Kumar Mishra, Uma Shankar, Ankit Jaiswal, Tarun Kumar Sharma, Prashant Kodgire, Amit Kumar

Abstract

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.

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