In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

Abstract

Background: The enterococcal surface protein (Esp) is a high-molecular-weight surface protein of biofilm creating agent in Enterococcus faecalis. Oxadiazoles have a wide range of biological activities. Objective: This research aimed to examine the impact of new oxadiazole derivatives on the expression of Esp, playing an important role in promoting the biofilm formation ability of drug-resistant E. faecalis strains. Method: 1, 3, 4-oxadiazole derivatives were synthesized through a one-step synthesis. E. faecalis strains were collected and isolated from hospitals in Tehran. The antimicrobial properties of the synthesized materials against the isolated strains were investigated. RNA, DNA, and cDNA were extracted, and the relative expression of Esp in E. faecalis isolates was evaluated by real-time PCR. Docking study was performed by AutoDock vina software, and the resulting docking poses were analyzed using Discovery Studio 4.5 Client software. Results: The use of synthesized derivatives changed the Esp expression level in different isolates compared to the control sample. The two compounds containing naphthalene (4f) and methoxyphenyl (4g) caused respectively a 2-fold and a 3-fold decrease in Esp expression compared to the control sample. The compound 4f with the best binding energy among the compounds (-9.2) had the most hydrogen and hydrophobic bonds with the receptor-binding site. Conclusions: 1, 3, 4-oxadiazole derivatives, especially naphthalene and methoxyphenyl, act as inhibitors of bacterial biofilm formation and can be used in the pharmaceutical and biological industries.

Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies

“…In the present study, terbinafine significantly reduced S. aureus ability to form biofilm on both polystyrene and polypropylene surfaces in a dose dependent manner. The naphthalene moiety incorporation has recently reported by Ghameshlouei et al [ 58 ] to improve biofilm inhibitory activity of oxadiazole derivatives. Terbinafine antibiofilm activity can be explained by its repressor effect on sarA and msaB , which have been strongly implicated in S. aureus biofilm formation.…”

Antibacterial and Antibiofilm Activity of Juglone Derivatives against Enterococcus faecalis: An In Silico and In Vitro Approach

“…Additionally, MOE can be used to build new applications that are based on SVL (Scientific Vector Language). The ligPlot implementation in MOE was utilized in order to make a prediction regarding the interaction of the enterococcal surface protein (Esp) with ligand molecules [ 24 ].…”

“…The .mdb file format was used to save all of the minimized versions of the molecules. The next step involved using the prepared ligands as input files for the MOE docking program [ 24 , 26 ].…”

“…The binding of the ligand molecules with the protein molecules was analyzed using MOE docking program to find the correct conformation of the ligands, so as to obtain minimum energy structure. After the completion of docking, we analyze the best poses for hydrogen bonding/ π − π interactions and root mean square deviation (RMSD) calculation by using MOE applications [ 24 ].…”

The Potential of 24-Propylcholestrol as Antibacterial Oral Bacteria of Enterococcus faecalis ATCC 29212 and Inhibitor Biofilms Formation: in vitro and in silico Study

“…Esp is a protein cell wall that plays a role in biofilm production by contributing to the bacteria’s surface colonization. 16 In addition, an inhibitor of GBAP synthesis is also a direct strategy to reduce virulence factors and prevent pathological damage from E. faecalis bacteria. GBAP is an autoinducer that interacts with receptors during the QS process.…”