Exploring Nature’s Treasure to Inhibit β-Barrel Assembly Machinery of Antibiotic Resistant Bacteria: An In silico Approach

Abstract

Background: The development of antibiotic resistance in bacteria is a matter of global concern due to the exceptionally high morbidity and mortality rates. The outer membrane of most gram-negative bacteria acts as a highly efficient barrier and blocks the entry of the majority of antibiotics, making them ineffective. The Bam complex, β-barrel assembly machinery complex, contains five subunits (BamA, B, C, D, E), which plays a vital role in folding and inserting essential outer membrane proteins into the membrane, thus maintaining outer membrane integrity. BamA and BamD are essential subunits to fulfill this purpose. Therefore, targeting this complex to treat antibiotic resistance can be an incredibly effective approach. Natural bacterial pigments like violacein, phytochemicals like withanone, semasin, and several polyphenols have often been reported for their effective antibiotic, antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Objective: Structural inhibition of the Bam complex by natural compounds can provide safe and effective treatment for antibiotic resistance by targeting outer membrane integrity. Methods: In-silico ADMET and molecular docking analysis was performed with ten natural compounds, namely violacein, withanone, sesamin, resveratrol, naringenin, quercetin, epicatechin, gallic acid, ellagic acid, and galangin, to analyse their inhibitory potential against the Bam complex. Results: Docking complexes of violacein gave high binding energies of -10.385 and -9.46 Kcal/mol at C and D subunits interface and at A subunits of the Bam complex, respectively. Conclusion: Henceforth, violacein can be an effective antibiotic against to date reported resistant gram-negative bacteria by inhibiting the Bam complex of their outer membrane. Therefore the urgent need for exhaustive research in this concern is highly demanded.