In silico identification of Corylifol C as a potential natural inhibitor of BfrB-Bfd interaction in Pseudomonas aeruginosa.

Abstract

Looking for potential alternatives to conventional antibiofilm agents has become a significant concern in treating drug-resistant Pseudomonas aeruginosa infections. In this study, we have tried to identify a potential natural antibacterial and antibiofilm compound against P. aeruginosa. Iron plays a crucial role in the virulence of P. aeruginosa biofilms. It is required for biofilm formation as well as for the production of the key virulence factors. The acquisition and utilization of iron within biofilms contribute to their resilience and ability to cause chronic infections. The interaction between Bacterioferritin (BfrB) and Ferredoxin (Bfd) in P. aeruginosa plays a crucial role in the mobilization of iron. Bfd facilitates the release of iron stored in BfrB, leading to the transfer of Fe²⁺ into the cytosol for bacterial metabolism. This process is vital for maintaining iron homeostasis and supporting various cellular processes. In our study, we have explored the potential of 27 antibacterial flavonoid compounds as ligands to inhibit the interaction between Bacterioferritin (BfrB) and Ferredoxin (Bfd). Through a series of computational analyses, including docking, MMGBSA, ADME, and MD simulation, we have identified Corylifol C as one of the most effective drug candidates capable of blocking the Bacterioferritin-Ferredoxin interaction. These findings suggest that Corylifol C may be used as a potential inhibitor to disrupt iron mobilization and may serve as a promising natural therapeutic agent. The study includes two reference compounds with known potential to block the Bacterioferritin-Ferredoxin interaction. Further wet-laboratory validation can help in establishing the antibacterial and antibiofilm properties of Corylifol C.