Homology Modelling and Virtual Screening of 3-deoxy-D-mannooctulosonic Acid Transferase of Aeromonas hydrophila as a Potential Target for Novel Natural Inhibitory Compounds

Abstract

Background: The fish pathogen Aeromonas hydrophila is fast acquiring resistance to commonly employed antibiotics in aquaculture. This development has compelled the aquaculture sector to identify and develop new therapeutics to manage the pathogen. Methods: In this study, the protein 3-deoxy-d-manno-2-octulosonic acid (Kdo) transferase of A. hydrophila involved in the biosynthesis of the cell wall was studied in-silico as a potential drug target to control this pathogen. The three-dimensional structure of Kdo transferase was predicted by homology modelling using the Modellar 9.15. A total of 7682 natural compounds and 55 known Gram-negative bacterial inhibitors were virtually screened. Laboratory evaluation of inhibitory effects of identified inhibitors against A. hydrophila was performed using extracts from tea leaves and Astragalus by standard disc diffusion method. Results: A molecular model of putative virulence factor Kdo was derived by homology modelling. Eleven compounds were found to be potential inhibitors of Kdo. Among natural compounds, LArabinose and Flavan-3,4-diol were identified as the putative therapeutic agents. In the disc diffusion test, the zones of inhibition were observed at 2 mg/ml concentrations for tea leaves extracts and 8 mg/ml for Astragalus, suggesting the inhibitory effects of these extracts. Conclusion: The study shows the utility of essential enzymes such as the protein Kdo transferase as a putative drug target and the potential application of natural compounds in the control of pathogens in aquaculture without the need to use synthetic antimicrobial compounds.