IN-SILICO DOCKING STUDIES OF PHYTO-LIGANDS AGAINST E. COLI PBP3: APPROACH TOWARDS NOVEL ANTIBACTERIAL THERAPEUTIC AGENTAbstract
Emergence of antibiotic resistance has become a serious problem worldwide. The extensive and uncontrolled use of antibiotics increases the number of multi drug resistant (MDR) bacterial strains. The major mechanisms that bacteria evolve to develop resistance against β-lactam class of antibiotics are the production of β-lactamases and expression of low affinity penicillin binding proteins (PBPs). These PBPs are involved in the final stages of peptidoglycan synthesis. Hence, PBPs are the primary targets for developing antibacterial agents as its inhibition leads to irregularities in cell wall structure and eventually cell death. Bioactive phytochemicals from medicinal plants have been proven to reveal important pharmacological and therapeutic properties for developing novel antibacterial agents. The current study epitomizes the binding of phytochemicals to the transpeptidation (TP) domain of PBP3 of E. coli, a major causative agent of bacterial infection. The phytochemicals exhibiting antibacterial activities were selected as ligands for docking studies employing Schrӧdinger Suite (Maestro, LLC, New York, NY, 2015). Amongst all the phytochemicals studied, chlorogenic acid (CGA) was found to have highest affinity towards PBP3 TP domain. The bocillin binding assay corroborated the docking analysis. The blocking of active site of PBPs by phytochemicals opens up new avenues for screening and developing new phytochemical-based therapeutic antibacterial agents.