Identification of Molecular Basis and Catalytic Specificity of TEM and CTX-M Extended-Spectrum β-Lactamase Resistance: An in silico study

Antibiotic resistance is at its peak to numerous antibiotics and has indeed necessitated exploring new potential targets and effective antibiotics. The prevalence of TEM and CTX-M type ESBLs poses a great threat to the clinical use of antibiotics for the treatment of severe infections. In this study, we have explored the catalytic binding speficity of antibiotics against TEM and CTX-M proteins that impose ESBL resistance. The TEM and CTX-15 proteins from E.coli, K.pneumoniae and P.aeruginosa were subjected to BLAST-P and Clustal W to identify the potential templates for homology modelling and models were built by using Modeller 9v9. The stereo chemical quality of the modeled protein has been validated by the PROCHECK analysis program using SAVS (Structure Analysis Verification Server). The docking analysis was carried out by using the Autodock tools (ADT) v1.5.4 and Auto dock v4.2 program. The docking analysis revealed the key amino acid residues within the catalytic sites of TEM & CTX-M-15 protein that has favored the interactions with specific antibiotics. Among the key residues that favored interactions, the amino acid residues SER, TYR and THR were found to be crucial in favoring the interactions with all the antibiotics. Thus the study provides the molecular insight of key amino acids from ESBL resistant strains which provides the path to design the novel inhibitors to overcome these long challenging ESBL resistances.