Design of novel hybrid secondary metabolite targets to diguanylate cyclase of Acinetobacter baumannii. (22nd November 2021)

• Record Type: Journal Article
• Authors: Tiwari, Monalisa; Joshi, Richa; Tiwari, Vishvanath
• Is Part Of: FEMS microbes. Volume 2(2021)
• Publication Date: 2021-11-22
• Subjects: Hybrid antibacterial molecule -- Acinetobacter baumannii -- Diguanylate cyclase -- Antibiofilm molecules -- Molecular dynamics simulation -- Hybrid secondary metabolite; Microbiology -- Periodicals; 579.05
• DOI: 10.1093/femsmc/xtab017
• Languages: English
• ISSNs: 2633-6685

Abstract

Abstract: Biofilm formation in bacteria is a resistance determinant and is positively regulated by cyclic diguanylate signaling. This signaling is a near universal signaling, and c-di-GMP produced by diguanylate cyclase (DGC) in this signaling is involved in different bacterial behaviors. The present study aims to find a plant-based novel hybrid therapeutic agent that can target the DGC of Acinetobacter baumannii . In this study, we have tried to design a hybrid molecule from the anti-biofilm plant secondary metabolites and screened its binding with the DGC of A. baumannii . The modeled and validated DGC was used to identify the active site and docking grid. Designed hybrid compounds were analysed for their interaction with the active site residues of DGC of A. baumannii . Further, the binding free energies of the docked complexes obtained from the Generalized Born model and Solvent Accessibility (MMGBSA) were analysed. The results indicated that VR-QEg-180 has a predicted high binding affinity with enzyme DGC as compared to other hybrids, parent secondary metabolites and positive control. Molecular dynamics simulation (MDS) analysis confirmed the interaction of VR-QEg-180 with DGC of the A. baumannii . The designed lead has favorable ADMET properties, has no human off-targets and has no predicted cytotoxicity in cell lines. Therefore, the designed hybrid molecule (VR-QEg-180) targeting the DGC of A. baumannii may play a very significant role in controlling this pathogen. Abstract : Designed hybrid anti-biofilm secondary metabolite targeting diguanylate cyclase mediated cyclic-di-GMP signaling in biofilm formation of Acinetobacter baumannii.