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
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.