In Silico Exploring of the Antibiotic Adjuvant Potential of some Natural Ligands in Carbapenem-Resistance Acinetobacter baumannii

A. baumannii is a gram-negative pathogen that has become one of the most important challenges in the world due to its high antibiotic resistance, and today many efforts are being made to treat infections caused by it. In recent years, there have been many concerns about increasing resistance to the beta-lactam antibiotic, carbapenem. Because resistance to these antibiotics greatly narrows the treatment options for the infections. The main source of carbapenem resistance in A. baumannii is the production of class D carbapenemase enzymes.

In this study, 27 plant ligands that have been shown to have antibacterial effects against A. baumannii and other resistant bacteria were selected. The chemical structure of the ligands and the three-dimensional structure of carbapenemase OXA-58 were extracted. The requirements of oral consumption of ligands were examined and ligand and OXA-58 docking were performed. 9 ligands including baicalein, berberine, curcumin, ellagic acid, epicatechin, honokiol, magnolol, norwogonin, and thymol, which met the requirements of Rule 5 and had better binding affinity than 6-alpha-hydroxymethyl penicillanate were selected. Redocking with a focus on the active position was performed by AutoDock software.

The amino acids involved in the hydrogen bonding of an antibiotic-representative ligand to the receptor were identified. Ligands that bind to at least one of these amino acids at the binding site by hydrogen bond were selected. Pharmacological and toxicity studies were performed and finally, the epicatechin ligand was introduced as the best ligand.

Plant ligands can be further investigated as promising antibiotic adjuvants and used in the future.