Comparison of transcriptome of E. coli K-12 wild type strain with transcriptome of E. coli K-12-R, highly tolerant to PPEF an antibacterial agent.

PPEF a small molecule which is a bacterial topoisomerase IA inhibitor and observed to be an effective bactericidal agent against both Gram-positive and Gram-negative bacterial strains and thus can be developed as potent broad-spectrum antibiotic against MDR bacterial strains. PPEF synthesis and bactericidal effects are published in JMC (Synthesis and biological evaluation of novel bisbenzimidazoles as Escherichia coli topoisomerase IA inhibitors and potential antibacterial agents. Nimesh H, Sur S, Sinha D, Yadav P, Anand P, Bajaj P, Virdi JS, Tandon V.J Med Chem. 2014 Jun 26;57:5238-57.) and Scientific Reports (Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazone combination against MDR bacterial strains. Sinha D, Pandey S, Singh R, Tiwari V, Sad K, Tandon V. Sci Rep. 2017 Mar 17;7:44419.) by our group. In the present project we want to evaluate the effect of PPEF on the genome of CGSC:5073 E.coli K12 (wild type), in order to understand the mechanism of action of this molecule. We want to see other than topoisomerase IA , what are the other genes in the bacteria are getting altered, mutated, any particular pathway is being upregulated or downregulated. We have observed that PPEF did not cause any mutation in topoisomerase IA, hence it becomes imperative to see is it stopping the source of energy to bacteria, because of that E. coli bacteria are dying.