IN SILICO MODELLING OF β-LACTAM RESISTANT ENTEROCOCCUS FAECALIS PBP4 AND ITS INTERACTIONS WITH VARIOUS PHYTO-LIGANDS
Keywords:
PBP4, Enterococcus faecalis, Autodock, Molecular dockingAbstract
Objective: The resistance to β-lactam antibiotics is a serious problem worldwide. This resistance has emerged due to two main mechanisms: production of β-lactamases that hydrolyses β-lactam antibiotics and other is the production of low affinity mutated Penicillin Binding Proteins (PBPs) that can sustain even at the high concentration of antibiotics. The current study epitomises the identification of T(425)S mutations in PBP4 of β-lactam resistant Enterococcus faecalis isolated from uropathological samples of urinary tract infected (UTI) patients. Also, the effect of the this mutation was analysed by in silico strategies on ligand binding efficiencies of the active site of PBP4 towards selected β-lactam antibiotics as well as phytochemicals.
Methods: To study the effect of T(425)S mutation towards emergence of antibiotic resistance pattern, the structural model was generated for wild-type and mutated PBP4 of E. faecalis using MODELLER and further studied the interactions of PBP4 with β-lactam antibiotics along with various phytochemicals identified and purified from selected medicinal plants possessing antibacterial activity using Autodock4 suite.
Results: Based on the results of different docking parameters and a number of H-bond interactions, gallic acid, and quercetin were identified with highest binding affinity to the active site pocket of PBP4 of E. faecalis, compared to β-lactam antibiotics. Further, molecular simulation studies also supported this fact.
Conclusion: T (425)S mutation has been identified with a significant change in ligand binding efficiencies towards tested β-lactam antibiotics. Moreover, gallic acid and quercetin have showed the possible antibacterial agent via blocking the active site of PBP4 of E. faecalis. The results presented here could be useful in designing more effective phyto-ligands based therapeutic antibacterial compounds against PBP4 of E. faecalis.
Keywords: PBP4, Enterococcus faecalis, Autodock, Molecular docking
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References
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