Inhibition of mecA and bla_CTX-M from MRSA and ESBL strains of diabetic foot infection by screening antibiotics compound library: an in silico analysis

A computational approach was exploited towards new molecule designing to target the inhibition of resistant genes mecA and blaCTX-M in MRSA and ESBL strains cultured from diabetic foot infected patients. The bioinformatic analysis involves the prediction of protein structures for mecA and blaCTX-M employing the Prime module of Schrodinger. The interactions were examined with the control antibiotics using the modelled protein structures, which revealed that Cefixime and Amikacin showed the highest binding affinity with mecA and blaCTX-M, respectively. According to the predictions of pharmacophores, the ADHRN hypothesis for mecA protein and the ADHR hypothesis for blaCTX-M protein were obtained. Subsequently, the antibiotic compound library from Selleckchem was retrieved, and molecular interactions studies were carried out to explore the interaction profiling of mecA with Tobramycin and blaCTX-M with Acyclovir. Further, the stability of protein-ligand interactions was validated through molecular dynamics simulations. Overall, this study suggests that the predicted pharmacophore model provides in-depth knowledge for repurposing an antibiotic drug with effective inhibition to enhance its therapeutic activity in the currently used ones.Communicated by Ramaswamy H. Sarma.