Genistein as a Potential Inhibitor of Tetrahydrofolate Biosynthesis in Combating Drug Resistance in Escherichia coli O157:H7

Objectives This study aims to determine the therapeutic value of various portions of the Vigna genus to manage, prevent, and treat bacterial diseases. Legumes are valuable as a source of protein and nutrients for most of the population. The excellent source of bioactive compounds from the legumes had drawn the investigator’s attention to identifying their pharmaceutical importance. To identify the potential bioactive compounds and pharmacological mechanisms associated with antimicrobial activity. This may help identify the novel antimicrobial resistance pathways in Escherichia coli (E.coli) O157: H7 to prevent the bacterium’s pathogenesis. Material and Methods The potential therapeutic applications of Vigna species ( n = 13) were uncovered using network analyses of bioactive compounds-protein targets in E. coli O157: H7, gene ontology (GO) enrichment, and pathway analysis. A total of 27 bioactive molecules among 172 from Vigna species were screened based on ADME (absorption, distribution, metabolism, and excretion) properties. The protein targets of bioactive compounds were identified through chemical-protein interaction and topological profiling. Results The chemical-protein interaction and topological profiling assist in identifying potential therapeutic targets (AcrA, AcrB, FolA, and RpoB) and are associated with bioactive compounds (myristic acid, methotrexate, quinolinic acid, daidzein, phaseolin, genistein, indole-3-aldehyde, and p-coumaric acid). Furthermore, gene enrichment and pathway analysis of the target proteins revealed their involvement is crucial in pathways like fatty acid biosynthesis, biotin metabolism, two-component system, bacterial chemotaxis, and RNA polymerase. Further, screening of the above bioactive compounds against all four protein targets revealed that genistein showed a good interaction with dihydrofolate reductase (DHFR) encoded by the folA gene, suggesting its inhibitory potential against antimicrobial resistance of E. coli . Conclusion Thus, these potent bioactive compounds with antibacterial activity would require in vitro/in vivo experimental analysis to develop them as potential compounds to treat antibacterial resistance in pathogens.