Rutin as a potential inhibitor to target peptidoglycan pathway of Staphylococcus aureus cell wall synthesis

Abstract

Bacterial cell wall synthesis pathway "Peptidoglycan Synthesis" is implicated in the development of antibiotics against various pathogens and provides an interesting target for therapeutic intervention. A medicinally valuable flavonoid "Rutin", have been shown to be effective against various pathogenic bacteria. Hence in this study, the prospective role of Rutin interaction in the capability against peptidoglycan synthesizing enzymes has been investigated, where the binding pattern of rutin with Mur ligases, MraY, FemX, FemA, FemB, and PBP2 have been studied. However, among them, Rutin interacted better with PBP2, which catalyze two important steps (transglycosylation and transpeptidation) of cell wall synthesis using TGase and TPase domains respectively. The interaction pattern and stability of Rutin towards both domains were studied individually through docking and simulation studies, which suggested that Rutin affinity towards TGase domain was more and similar to the reference molecule Moenomycin, compared to the TPase domain. Thus, were reported herein, Rutin as a novel structural class for inhibitor development based on the results which provided better insights on the interactional studies against S. aureus by targeting TGase domain of PBP2.