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

Abstract

A computational approach was exploited towards new molecule designing to target the inhibition of resistant genes mecA and bla_CTX-M in MRSA and ESBL strains cultured from diabetic foot infected patients. The bioinformatic analysis involves the prediction of protein structures for mecA and bla_CTX-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 bla_CTX-M, respectively. According to the predictions of pharmacophores, the ADHRN hypothesis for mecA protein and the ADHR hypothesis for bla_CTX-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 bla_CTX-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

Keywords:

• Diabetic foot infection
• Staphylococcus aureus
• Pseudomonas aeruginosa
• mecA
• blaCTX-M
• pharmacophore
• molecular dynamics simulations

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.