Inhibition of penicillin-binding protein 2a (PBP2a) in methicillin resistant Staphylococcus aureus (MRSA) by combination of oxacillin and a bioactive compound from Lichen Ramalina roesleri

Lichens are known to be useful and important in ethanopharmacology since ages and still possess substantial interest in alternative medical practices around the world. The intent of the investigation was to evaluate and to understand the antibacterial potential of usnic acid which was isolated from Himalyan fruticose lichen Ramalina roesleri. Usnic acid is predicted for its pharmaceutical properties through in -silico studies. Binding efficiency of usnic acid with Penicillin binding protein-PBP2a, a protein responsible for conferring resistance in Staphylococcus aureus was accessed using in-silico interaction assays. Further, validation of the study was checked by determining the potential of usnic acid against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. In total, 28 clinical isolates collected from a hospital were included in the study and the anti-Staphylococcal activity was determined using agar plate dilution method followed by time-kill kinetics and synergistic studies. Docking results clearly indicated that usnic acid exhibited remarkable binding which is better than the energy range of reference compound oxacillin and comparable to the co-crystallized ligand ceftaroline. The minimum inhibitory concentrations (MICs) of usnic acid against the clinical isolates of MRSA and reference strain (NCTC-6571) were in the range of 32-128 μg/ml. The high affinity to bind with PBP2a obtained through in silico studies could be further confirmed by the strong effect of usnic acid on MSRA clinical isolates.