Molecular exposition of broad-spectrum antibacterial efficacy by p-coumaric acid from an edible mushroom Termitomyces heimii: in vitro and in silico approach

Abstract

P-Coumaric acid was previously reported to contain antioxidant, antidiabetic, anti-inflammatory, antiplatelet, antiulcer and anticancer activities. Along with these, the present work has been conducted to study the antibacterial activity of p-coumaric acid. It could be used to control broad-spectrum microbiome-based inflammation or in cancer control. HPLC analysis of methanolic extract from the mushroom Termitomyces heimii has exhibited a rich fraction of p-coumaric acid (p-CA), which in the pure form showed significant bactericidal potentials. To predict the molecular interactions associated with the bactericidal mechanism of p-CA, the transmembrane protein sequences of Staphylococcus aureus and Escherichia coli were retrieved from the IMG–JGI database, screened and then aligned using Clustal X2 and PHYLIP 3.69 softwares. The common sequences were subjected to tertiary structure prediction using Phyre2 server, followed by quality assessment through the Ramachandran plot. Next, the 3D molecular structure of p-CA was downloaded from PubChem and docked with the selected tertiary structures using Patchdock and showed higher affinity towards 12 common transmembrane protein structures, amongst which CDP-diacylglycerol–glycerol-3-phosphate 3-phosphatidyl transferase (PgsA) exhibited best docking with p-CA on the basis of ACE value (– 249 kcal/mol). This fact revealed that p-CA can block the normal functioning of membrane-bound enzyme PgsA, consequently leading to the interruption in the synthesis and recycling of an essential membrane component phosphatidylglycerol (PG), resulting in membrane disruption followed by cell lysis. Here, for the first time we reported the molecular insights and fundamental biochemical events underlying the bactericidal action by p-CA, to explore new perspective to combat multidrug-resistant bacteria.