Differential analysis of whole genome sequencing (WGS) of Staphylococcus aureus 25923 in presence and absence of PPEF
PPEF is a known antibacterial agent that acts as a type IA topoisomerase inhibitor. We have observed PPEF as a potent molecule which could inhibit the growth of different bacteria irrespective of the nature of their cell wall. The efficacy of antimicrobial activity of PPEF against methicillin-sensitive S. aureus (MSSA), MRSA, and vancomycin-resistant S. aureus (VRSA) is reflected by its low MIC and MBC. The S. aureus strain ATCC 25923 has been evolved in a dose-dependent manner against PPEF. Over 440 generations, its MIC90 increased to 16-fold denoted as Staphylococcus aureus PPEF Resistance (SA-PR). Whole genome analysis was performed for SA-PR in comparison with SA-GC (Staphylococcus aureus Growth Control). S. aureus ATCC 25923 (MSSA), a closely related non-pathogenic species, were pivotal in the identification of protein-coding genes essential for PPEF resistance. However, no comprehensive comparison has focused on the non-coding genome. The SA-PR became sensitive to commercial antibiotics. Overall, this study provides insights into the existence of diverse evolutionary pathways of S. aureus for tolerance and resistance development against PPEF. PPEF synthesis and its 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.), 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.) and Communication Biology (Unraveling topoisomerase IA gate dynamics in presence of PPEF and its preclinical evaluation against multidrug-resistant pathogens. Maurya V, Singh R, Singh RK, Pandey S, Yadav P, Parashar P, Gaind R, Dubey KD, Naresh Patwari G, Tandon V., 2023 Feb 18;6(1):195.) by our group.